Preface

WHO’s revised drug strategy, as adopted in resolution WHA39.27 of the Thirty-ninth World Health Assembly in 1986, calls for the preparation of model prescribing information which is being developed to complement WHO’s Model List of Essential Drugs.1 The objective is to provide up-to-date source material for adaptation by national authorities, particularly in developing countries, that wish to develop national drug for- mularies, drug compendia and similar material.2

The information is to be regarded as illustrative rather than normative. It is appreciated that it is not possible to develop an information sheet on a specific drug that is appropriate to circumstances prevailing in each of WHO’s Member States and that some countries have already formally adopted texts of their own that have a statutory connotation.

This volume has been reviewed by internationally accredited experts and by certain nongovernmental organizations in official relations with WHO, including the International Feder- ation of Pharmaceutical Manufacturers Associations, the Inter- national League of Infectious Diseases and the International Society of Chemotherapy.

1 The use of essential drugs. Ninth report of the WHO Expert Committee (including the revised Model List of Essential Drugs). Geneva, World Health Organization, 2000 (WHO Technical Report Series, No. 895). 2 For details of volumes already published, see inside back cover.

1 WHO Model Prescribing Information — Drugs used in bacterial infections

Drug dosage Most drug doses are given per kilogram of body weight or as fixed doses calculated for adults of 60kg. Storage conditions Readers are referred to The International Pharmacopoeia, 3rd edition, Vol. 4 (Geneva, World Health Organization, 1994) for definitions concerning containers for drugs. Abbreviations used i.m. intramuscularly i.v. intravenously

2 Introduction

Although many communicable diseases have been effectively contained, bacterial infections remain a major cause of mor- bidity and mortality, particularly in developing countries. Moreover, in both developed and developing countries, the risk of some serious bacterial infections has increased because of treatments such as chemotherapy for cancer and the emer- gence of diseases such as human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS), which impair the patient’s defences against infection.

Antimicrobials have reduced the morbidity and improved the survival of patients with bacterial infections and remain es- sential for the treatment of many kinds of bacterial disease. However, the increasing prevalence of strains of common pathogenic bacteria resistant to widely available, affordable antimicrobials is, in many cases, dangerously eroding their effectiveness. It is hoped that by encouraging the appro- priate use of antimicrobials, the emergence and spread of anti- microbial resistance may be delayed. Resistance to antimicrobials The prevalence of antimicrobial resistance among pathogenic bacteria is increasing both among hospital patients and in the community. The emergence of such resistance may in part depend on the acquisition of new mechanisms of interference with antimicrobial activity and on the spread of resistant iso- lates between patients. Selection of resistant bacteria Resistance may be due to the following mechanisms: • Transfer of genes containing DNA coding for antimicrobial resis- tance located either on plasmids or on transposons. Enteric bacteria are a common source of such genes, which have appeared in many species, including Neisseria gonorrhoeae and Haemophilus influenzae.

3 WHO Model Prescribing Information — Drugs used in bacterial infections

• Spontaneous mutation of bacteria. Selection of resistant variants allows a pre-existing resistant strain to emerge following treatment with an antimicrobial agent acting against suscep- tible organisms. For example, patients with staphylococcal infections treated with rifampicin alone often develop resis- tant staphylococcal isolates within a few days. A minor pro- portion of enteric bacteria may be resistant strains capable of producing high-level b-lactamases which are readily selected by cefalosporins, broad-spectrum penicillins and monobac- tams. Some bacterial species are heterogeneously resistant to fluoroquinolones and can, consequently, be selected by the drugs. • Antimicrobial-induced effects on the normal microflora. Treat- ment with antimicrobials results in susceptible species be- coming less common and naturally resistant species more frequent. Genes responsible for such resistance among species of the normal flora can be transferred to pathogens causing infections. It is thought that penicillin-resistant Strep- tococcus pneumoniae and vancomycin-resistant enterococci arose by such a transformation. The selection of resistant bacteria is minimized by adherence to a few basic principles: — use antimicrobials that are most appropriate for the cause of infection and the prevalence of local resistance; — use adequate doses; — ensure that the treatment course is completed. For most bacterial infections a single antimicrobial is all that is required. However, in some circumstances combination therapy with two or more agents with different mechanisms of activity may be needed to minimize the emergence of resistance among certain species — for example in the treatment of infec- tions caused by Mycobacterium tuberculosis. Spread of resistant bacteria The spread of antimicrobial-resistant bacteria was once consid- ered to be mainly a problem associated with poor hygiene in hospitals. Poor hygiene contributes to the spread of resistant strains of bacteria, as has been demonstrated by reports of hospital-acquired (nosocomial) infections over recent years.

4 Introduction

The introduction of a number of hygienic measures, including improved facilities for hand-washing, isolation of patients with multiresistant bacteria and improved aseptic techniques for invasive procedures has reduced the spread of pathogenic bacteria in hospitals.

The spread of antimicrobial-resistant strains in the community has presented problems in the treatment of infections of the res- piratory tract, gastrointestinal tract, urinary tract, skin and soft tissues as well as in the treatment of some sexually transmitted diseases and meningitis. In many communities it is difficult to maintain hygienic procedures. Childhood infections are common in the community because transfer of microorganisms occurs readily. Antimicrobial-resistant bacteria are also readily spread by and between children.

The breakdown of infrastructure that frequently occurs in situ- ations of armed conflict, famine and economic crisis also leads to outbreaks of infection. Such outbreaks are increasingly caused by bacteria with acquired resistance to antimicrobials.

Although hygienic measures are the main method for control- ling the spread of antimicrobial-resistant as well as antimicro- bial-susceptible bacteria, inappropriate use of antimicrobials also needs to be addressed. Inappropriate uses include the administration of antimicrobials when their use is not indicated and use of antimicrobials to which the pathogens are already resistant. The use of inappropriate antimicrobials, suboptimal doses, the wrong duration of treatment and excessive use of one particular class of drugs will also increase the prevalence of resistance. Problems such as uncontrolled access to anti- microbials and varying quality of some products may also in- crease the prevalence of resistance. Role of laboratories in antimicrobial susceptibility testing and reporting of surveillance data The majority of bacterial infections are treated on the basis of a presumptive etiological diagnosis determined by the clinical history and physical findings. Empirical therapy should be

5 WHO Model Prescribing Information — Drugs used in bacterial infections

based on local epidemiological data on likely pathogens and their patterns of antimicrobial susceptibility. For this reason, capacity for testing the antimicrobial susceptibility of priority pathogens, including those causing infection in the commun- ity, should preferably be available in several laboratories in different geographical locations in all countries. As a mini- mum, testing must be carried out in a national reference laboratory. Data should be collected on Staphylococcus aureus, Pseudomonas aeruginosa and Enterobacteriaceae. Information about community-acquired infections is usually more difficult to obtain, but data should be collected on Streptococcus pneu- moniae, Streptococcus pyogenes, Escherichia coli and Salmonella and Shigella spp. A limited range of antimicrobials is important for different organisms. For Streptococcus pneumoniae, for example, information on resistance to benzylpenicillin, cefalosporins, sulfamethoxazole + trimethoprim, erythromycin and chloramphenicol has the highest priority. Information on antimicrobial resistance in Mycobacterium tuberculosis and Neis- seria gonorrhoeae is also important.

Laboratories should apply internationally recognized methods of antimicrobial susceptibility testing and should ensure that the results are analysed and communicated appropriately in order that empirical treatment guidelines can be updated. There should be a well-functioning system of quality control in place. WHO has a software package (WHONET)1 available to laboratories on request for epidemiological analysis of anti- microbial susceptibility data and can assist in the provision of laboratory training.

Not all infections require specific antimicrobial treatment and careful clinical judgement is essential to determine whether symptomatic treatment is sufficient. Microbiological investiga- tions should always be carried out before treatment where pos- sible when the etiology is uncertain, in severe infections when patients fail to respond to empirical therapy or develop a new infection during the course of treatment, or for public health purposes. Appropriate specimens for Gram-staining, culture

1 Available on request from Anti-infective Drug Resistance and Containment, Communicable Disease Surveillance and Response, World Health Organization, 1211 Geneva 27, Switzerland.

6 Introduction

and susceptibility testing should be obtained before starting antimicrobial therapy. In many situations microbiological iden- tification of the pathogen is vital to determine the appropriate antimicrobial treatment. In contrast, group A b-haemolytic streptococci are routinely susceptible to benzylpenicillin and phenoxymethylpenicillin, making mandatory susceptibility testing unnecessary. General principles of antimicrobial prescribing Spectrum of activity Ideally, the antimicrobial susceptibility of an organism should be known and the most effective and safe agent targeted to the infection should be used. This reduces the likelihood of selec- tion of resistant microorganisms and superinfection. However, in most cases the suspected organism is assumed to be suscep- tible to a particular antimicrobial because of its known charac- teristics from surveillance data. Pharmacokinetics and pharmacodynamics The pharmacokinetics and pharmacodynamics of an anti- microbial are determined by three factors: the serum half-life, its distribution in the body tissues and fluids (e.g. cerebrospinal fluid) and its accumulation in phagocytic cells. The dosage should be consistent with the drug’s half-life (e.g. a single daily dose for drugs with a serum half-life of 10–20 hours). Drugs that achieve high intracellular levels are necessary for infec- tions with intracellular pathogens such as Chlamydia and Legionella spp. and Coxiella burnetti. For most infections the con- centration of drug in the infected site (e.g. interstitial fluid, urine) is a key pharmacokinetic parameter. Binding of a small fraction of the drug to serum proteins contributes to the achievement of high extravascular concentrations; conversely, serum protein binding levels above 80–85% have an impact on passage from the blood to extravascular compartments, but are not per se indicative of tissue concentrations below therapeu- tic levels. In patients with renal or hepatic impairment, reduc- tion of the dose may be required. Oral versus parenteral administration Antimicrobials should be administered by the most appropri- ate route in an optimum dose, since inadequate plasma levels

7 WHO Model Prescribing Information — Drugs used in bacterial infections

may lead to the development of resistance. Some clinical cir- cumstances (e.g. patients who are severely ill or who have col- lapsed, or those with impaired bowel function) may require the use of parenteral antimicrobials. The excellent absorption of many oral antimicrobials (including b-lactams, chlorampheni- col, doxycycline and fluoroquinolones) and the associated cost- benefits make oral administration usually the most appropriate form of antimicrobial therapy. Adherence and ease of administration Oral formulations are more convenient, generally cheaper and associated with less adverse effects than parenteral ones. Par- enteral formulations also require trained medical staff for their administration and can have specific adverse effects not seen with orally administered drugs. Oral drugs with fewer doses are preferred. The appropriateness of the choice of drug for individual patients also depends on factors such as the patient’s age, the presence of underlying disease, renal or liver impair- ment or allergies, concurrent therapy and whether the patient is pregnant. Impact on normal microbial flora If two antimicrobial agents have similar probable cure rates, cost and tolerance in a particular case, the agent having the least deleterious impact on the normal human microbial flora should be chosen. This may reduce or prevent adverse effects such as antimicrobial-associated diarrhoea and vaginal super- infections with Candida spp. Cost of treatment The drug with the lowest cost is preferred if efficacy, adherence and tolerance are comparable. However, the cost of the total treatment, and not only the unit cost of the drug, must be considered. Antimicrobial combinations In certain clinical settings it may be necessary to use two or more antimicrobials to achieve the desired effect. The common indications for combination therapy are: • to obtain antimicrobial synergy (i.e. an effect unobtainable with either drug alone);

8 Introduction

• to delay the development of resistance; • to broaden the spectrum of antimicrobial activity against an infection of unknown etiology or involving more than one species. Effect of commercial promotion Individuals responsible for prescribing drugs and drug com- mittees are commonly subject to commercial promotion in making choices about antimicrobials. Objective data and evi- dence of clinical efficacy should provide the basis for decisions for including antimicrobials in drug formularies. Drug formularies The list of antimicrobials to be included in the drug formulary of an institution should be established by consensus among the users in the institution represented in the drug committee (e.g. physicians, pharmacists, clinical pharmacologists, microbiolo- gists and nurses). For each particular antimicrobial, the clinical indication (therapeutic, prophylactic or empirical) and the dosage (for adults, children and, if appropriate, patients with hepatic or renal impairment) must be mentioned. Objective information should be distributed by the committee, based on data from the manufacturer and independent drug informa- tion. The committee should conduct periodic evaluations of the functioning of the formulary. Choice of antimicrobial and options for treatment In this book, the recommendations for initial empirical treat- ment of infection are based on current knowledge of the preva- lence of antimicrobial resistance. Most infections are treated initially on the basis of clinical evidence, without full knowl- edge of the causative organism or its susceptibility. As the prevalence of resistance varies considerably from one commu- nity to another, the recommendations are presented as a series of options. The local choice of an option for treatment will be influenced by the prevalence of resistance (where known), the availability and tolerability of the antimicrobial, and the cost of a full course of treatment. The range of antimicrobials listed in this book conforms, in the main, to the WHO Model

9 WHO Model Prescribing Information — Drugs used in bacterial infections

List of Essential Drugs1 and to other recent publications by WHO.2–5

Rational use of the many different classes of antimicrobials depends on the points discussed above. Because of the incon- sistent availability of drugs and the variation in the needs of patients — in turn a result of differences in age, hypersensitiv- ity and factors influencing metabolic fate in the body — options are given rather than a single “best choice”. The range of antimicrobials is wide but most conditions can be managed using well-established drugs rather than the newest ones.

Some institutions restrict certain antimicrobials as “reserve” agents. A reserve antimicrobial is one that is useful for a wide range of infections but, because of the need to reduce the risk of development of resistance and because of its relatively high cost, it would be inappropriate to recommend its unrestricted use. The drug should be included in the drug formulary of the institution with the clinical indications clearly defined and be made available without delay when needed. It should have restricted availability and be prescribed only under the super- vision of a senior medical officer. Within this context the b- lactam drugs, the fluoroquinolones and vancomycin are particularly important. b-Lactam antimicrobials Resistance to b-lactam antimicrobials is generally due to the production of b-lactamases in staphylococci, enterobacteria, Haemophilus spp., gonococci and Pseudomonas spp. In several of

1 The use of essential drugs. Ninth report of the WHO Expert Committee (including the revised Model List of Essential Drugs). Geneva, World Health Organization, 2000 (WHO Technical Report Series, No. 895). 2 WHO model prescribing information: drugs used in sexually transmitted diseases and HIV infection. Geneva, World Health Organization, 1995. 3 WHO Expert Committee on Malaria. Twentieth report. Geneva, World Health Organization, 2000 (WHO Technical Report Series, No. 892). 4 Gilles HM. Management of severe malaria: a practical handbook, 2nd ed. Geneva, World Health Organization, 2000. 5 The use of artemisinin and its derivatives as antimalarial drugs: report of a Joint CTD/DMP/TDR Informal Consultation, Geneva, 10–12 June 1998. Geneva, World Health Orga- nization, 1998 (unpublished document WHO/MAL/98.1086; available from Communicable Disease Research and Development, World Health Organization, 1211 Geneva 27, Switzerland).

10 Introduction

these species and in others such as Streptococcus pneumoniae and enterococci, non-enzymatic mechanisms also occur. Many new b-lactam antimicrobials are included in the WHO Model List of Essential Drugs as reserve antimicrobials. In order to preserve the activity of these antimicrobials it is recommended that these agents are used only where rates of resistance to all normally appropriate essential drugs are high or for specific indications, as listed below.

The b-lactamase inhibitor amoxicillin + clavulanic acid is resis- tant to degradation by many of the enzymes produced by entero- bacteria and Bacteroides spp. A specific indication for its use is in polymicrobial infections related to surgical conditions of the intestinal tract and female genital tract. Amoxicillin remains active against many common bacteria such as b-haemolytic streptococci and a high proportion of strains of Haemophilus influenzae in many countries. The emergence of strains of Strep- tococcus pneumoniae with reduced susceptibility to penicillins does not at this time justify replacement of this group of anti- microbials for the treatment of respiratory tract infections.

Many parenteral cefalosporins active against Gram-negative and Gram-positive bacteria are now widely used for the treat- ment of infection. WHO’s Model List of Essential Drugs includes ceftriaxone as a reserve agent for the treatment of meningitis due to Streptococcus pneumoniae in areas where the incidence of resistance to penicillins is high. It has been listed as an example of a therapeutic group because the results of clin- ical trials indicate that cefotaxime is equally effective and may be preferred in some hospitals or treatment centres. Ceftriax- one is specifically recommended for the treatment of gonor- rhoea and chancroid where resistance to other antimicrobials is common. At its eighth meeting in 1997,1 the WHO Expert Com- mittee on the Use of Essential Drugs noted that several other cefalosporins such as cefuroxime are widely used for chemo- prophylaxis in surgery and for the treatment of respiratory infections. These cefalosporins are not as effective as ceftriax- one or cefotaxime in the treatment of meningitis due to

1 The use of essential drugs. Eighth report of the WHO Expert Committee. Geneva, World Health Organization, 1998 (WHO Technical Report Series, No. 882).

11 WHO Model Prescribing Information — Drugs used in bacterial infections

Streptococcus pneumoniae. However, they may be used as alter- natives for chemoprophylaxis in surgery or for treatment of res- piratory infections in areas of penicillin resistance.

Chemoprophylaxis in surgery should be limited to the minimum number of doses required to ensure efficacy, usually one or two. Ceftriaxone and cefotaxime should never be used for chemoprophylaxis.

Ceftazidime is included in WHO’s Model List of Essential Drugs because it is active against Pseudomonas aeruginosa. It is recommended that it should be used when the prevalence of resistance to gentamicin is high or when resistance to gentami- cin only has been documented in a particular patient.

Imipenem + cilastatin is a broad-spectrum b-lactam antimicro- bial included as a reserve agent for the treatment of severe infections with Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter spp. resistant to all normally appropriate antimicrobials. Such resistant organisms are usually only found in tertiary care hospitals and, in particular, in intensive care units where antimicrobial usage is high. Fluoroquinolones Ciprofloxacin is a member of the fluoroquinolone family of antimicrobials. Although it is now listed as an essential drug, the comparative costs of alternative broad-spectrum products will be an important determinant of selection. Ciprofloxacin and certain other fluoroquinolones may still be considered of value as reserve agents. Their use may need to be restricted to the following circumstances: • For typhoid fever and other systemic salmonella infections where strains of Salmonella spp. exist that are resistant to chloramphenicol, amoxicillin and sulfamethoxazole + trimethoprim. • For severe shigellosis where Shigella spp. strains exist that are resistant to ampicillin, chloramphenicol, sulfamethoxazole + trimethoprim, tetracyclines and nalidixic acid. • For gonorrhoea and chancroid, as alternatives to cefalo- sporins, when oral administration is appropriate.

12 Introduction

• For certain hospital-acquired infections due to Gram- negative bacilli, including Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa, that are resistant to essential drugs such as amoxicillin, chloramphenicol and gentamicin. Vancomycin Meticillin-resistant strains of Staphylococcus aureus are usually resistant to all b-lactam antimicrobials and also to structurally unrelated drugs such as erythromycin, clindamycin, chloram- phenicol, the tetracyclines and the aminoglycosides. The only effective reserve drug for infections due to these multiresistant organisms is vancomycin, which is expensive and must be administered intravenously. Alternative agents Many drugs included in WHO’s Model List of Essential Drugs are preceded by a square symbol () to indicate that they rep- resent an example of a therapeutic group and that various drugs could serve as alternatives. It is imperative that this is understood when drugs are selected at a national level, since choice is then influenced by the comparative cost and availability of equivalent products. Examples of acceptable substitutions include: ciprofloxacin: ofloxacin. cloxacillin: flucloxacillin, nafcillin, oxacillin or dicloxacillin. ceftriaxone: cefotaxime. cefazolin: cefalotin. cefalexin: cefradine. Although these drugs are comparable, the doses may vary.

13 Upper respiratory tract infections

Infections of the upper respiratory tract represent the most common cause of antimicrobial use. The vast majority of such infections are of viral origin and do not require treatment with antimicrobials. Because of the potential misuse of anti- microbials in these conditions, some agents are specifically not recommended. Acute pharyngitis Most cases of pharyngitis are caused by viruses and do not require treatment with antimicrobials. The most common bacterial causes of pharyngitis are Streptococcus pyogenes (which may be associated with acute rheumatic fever) and Corynebacterium diphtheriae.

It may be difficult to distinguish between streptococcal and viral pharyngitis on clinical grounds alone. Tender, enlarged cervical lymph nodes and a scarlet fever-like rash are consid- ered specific for S. pyogenes, but uncommon. Presence of the three major signs (fever >38°C, intense pharyngeal pain, and absence of rhinitis and cough) has a high positive-predictive value for streptococcal pharyngitis. When these three signs are not all present, streptococcal etiology is unlikely. A rapid antigen test and culture techniques are available for the diag- nosis of S. pyogenes infection, allowing specific therapy, but may not be cost-effective in certain circumstances. Other strepto- coccal serogroups (e.g. serogroups B, C and G) have also been associated with infections, but they do not cause rheumatic fever. In some cases peritonsillar abscesses may develop and surgical drainage may be needed. Routine testing for allergy to penicillins is not considered necessary.

Treatment Benzathine benzylpenicillin 1.2 million IU i.m. in a single dose for adults and children >30kg (children £30kg: 30000IU/kg (maximum 1.2 million IU) i.m. in a single dose)

14 Upper respiratory tract infections

or phenoxymethylpenicillin 500mg (children: 10–20mg/kg; maxi- mum 500mg) orally every 6 hours for 10 days or amoxicillin 500mg (children: 15mg/kg; maximum 500mg) orally every 8 hours for 10 days.

Patients allergic to penicillins Erythromycin 500mg (children: 10–15mg/kg; maximum 500mg) orally every 6 hours for 10 days or cefalexin 500mg (children: 15mg/kg; maximum 500mg) orally every 6–8 hours for 10 days.

Comments Fluoroquinolones, tetracyclines, sulfamethoxazole + trimetho- prim and combinations with aminopenicillins and b-lactamase inhibitors are not recommended. Nasopharyngitis, rhinitis and common cold Nasopharyngitis is characterized by the presence of rhinitis and pharyngitis with fever. It is very common in young children. The cause is viral and no antimicrobials are required in most cases for either treatment or chemoprophylaxis. Antipyretics (not aspirin in children) can be given to control high fever.

Rhinitis of bacterial origin, including diphtheria in infants (see page 19), can occur. The common cold is caused by viruses and does not require treatment with antimicrobials. Otitis media Acute otitis media Upper respiratory tract infections of viral origin are frequently associated with mild redness of the tympanic membrane, but antimicrobials are generally not necessary. Acute otitis media, however, is an infection of the middle ear that occurs mostly in infants and children under 2 years of age. The bacterial

15 WHO Model Prescribing Information — Drugs used in bacterial infections

pathogens most often implicated are Streptococcus pneumoniae and Haemophilus influenzae. Vaccination against the latter pathogen has significantly reduced the recurrence of H. influen- zae. Bacterial infection is suggested by the presence of acute onset of pain in the ear, fever, and redness and decreased mobil- ity of the tympanic membrane. Patients presenting with these signs require antimicrobials; meningitis can be a complication.

Treatment Amoxicillin 500mg (children: 15mg/kg; maximum 500mg) orally every 8 hours for 5 days or amoxicillin 500mg + clavulanic acid (children: amoxicillin 7.5–15mg/kg + clavulanic acid; maximum 500mg) orally every 8 hours for 5 days or sulfamethoxazole 400mg + trimethoprim 80mg (children: 20mg/kg + 4mg/kg; maximum 400mg + 80mg) orally every 12 hours for 5 days.

Comments Amoxicillin + clavulanic acid is preferred in regions where b- lactamase-producing strains of H. influenzae are common. In a few regions, the incidence of penicillin-resistant S. pneumoniae is increasing. For this reason, higher doses of amoxicillin and amoxicillin + clavulanic acid are the treatment of choice. However, these penicillin-resistant strains are frequently also resistant to sulfamethoxazole + trimethoprim. For patients who are allergic to penicillins, cefuroxime axetil (250–500mg orally every 12 hours for 5 days) is another alternative.

Erythromycin, tetracyclines, fluoroquinolones and most oral cefalosporins are not recommended. Chronic otitis media Chronic otitis media is characterized by a history of chronic dis- charge from one or both ears. If the eardrum has been ruptured for more than 2 weeks, secondary infection with a variety of organisms is common. Antimicrobial therapy is generally not recommended. The ear should be thoroughly washed with

16 Upper respiratory tract infections

clean water once daily and then dried three times daily for several weeks (until it remains dry). Acute mastoiditis Acute mastoiditis is a bone infection characterized by painful swelling behind or above the ear. It may be complicated by meningitis. The patient should be admitted to hospital, anti- microbials commenced and surgery considered.

Treatment Chloramphenicol 1g (children: 25mg/kg; maximum 750mg) i.v. or i.m. every 6–8 hours for 10–14 days or ampicillin 2g (children: 25–50mg/kg; maximum 2g) i.v. every 6 hours for 10–14 days or ceftriaxone 1g (children: 50mg/kg; maximum 1g) i.v. or i.m. every 12 hours for 10 days.

Intravenous formulations of ceftriaxone should be adminis- tered over at least 2 minutes. Acute sinusitis Acute sinusitis usually occurs as a complication of viral infec- tions of the upper respiratory tract, although a small propor- tion of cases are associated with dental infections. It may also occur in patients with allergic rhinitis. Persistent purulent nasal discharge, sinus tenderness, facial or periorbital swelling and persistent fever are characteristic symptoms. Cough may also be present.

In adults, the presence of persistent purulent nasal discharge alone (with or without cough) is not an indication for anti- microbial therapy. However, antimicrobials should be consid- ered if sinus tenderness, facial or periorbital swelling, or persistent fever are also present. Therapy should be primarily directed against S. pneumoniae and H. influenzae and is therefore similar to that recommended for acute otitis media, except that it should be continued for 7–10 days. Fluoroquinolones and most cefalosporins are not recommended.

17 WHO Model Prescribing Information — Drugs used in bacterial infections

Croup (laryngotracheobronchitis) Croup is a clinical syndrome characterized by inflammation of the larynx and trachea. It involves primarily children under 3 years of age and is commonly preceded by an upper respira- tory tract infection. It has a more gradual onset than epiglotti- tis. In many developed countries, croup is caused by viruses such as parainfluenza or influenza virus. Secondary bacterial infection is rare and antimicrobials are rarely indicated. However, severe cases should be treated as for epiglottitis (see below). Epiglottitis Epiglottitis presents as an acute, severe infection of the epiglot- tis and aryepiglottic folds accompanied by fever, a cherry red epiglottis and drooling. Severe disease is characterized by stridor, chest indrawing, hoarseness and inability to swallow. The patient should be admitted to hospital. Airway obstruction is always severe and intubation or tracheostomy is often needed. Antimicrobial treatment should be directed against the most common pathogen, H. influenzae serotype b.

Treatment Adults and children > 2 months Chloramphenicol 1g (children >2 months: 25mg/kg; maxi- mum 1g) i.v. or i.m. every 6 hours for 5 days or ceftriaxone 2g (children >2 months: 100mg/kg; maximum 2g) i.v. or i.m. every 24 hours for 5 days.

Intravenous formulations of ceftriaxone should be adminis- tered over 2 minutes.

Neonates Cefotaxime 50mg/kg (maximum 2g) i.v. or i.m. every 8 hours for 5 days.

Comments Neither chloramphenicol nor cefotaxime eliminates carriage of H. influenzae serotype b and a course of rifampicin 600mg (neonates <1 month: 10mg/kg (maximum 300mg); children

18 Upper respiratory tract infections

≥1 month: 20mg/kg (maximum 600mg)) orally every 24 hours for 4 days is therefore recommended if either of these agents is used. Rifampicin treatment is not necessary if ceftriaxone is used.

In young children, consideration should be given to vaccina- tion against H. influenzae serotype b (Hib). Diphtheria Laryngeal diphtheria may present with symptoms that include local manifestations (pharyngeal, laryngeal, tracheobronchial or cutaneous) and distant manifestations, in particular neuro- logical effects secondary to dissemination of the diphtheria toxin. Presumptive diagnosis is based on epidemiological data and several clinical signs, including mildly painful pharyngitis with extending greyish adherent membrane, adenopathy, cer- vical swelling, paralysis of the palate, a harsh cough and a hoarse voice. The patient should be admitted to hospital. Diph- theria antitoxin 20000–100000IU should be given immediately. If airway obstruction is severe, intubation or tracheostomy may be needed.

Treatment Diphtheria antitoxin 20000–100000IU i.v. or i.m. immediately

followed by either procaine benzylpenicillin 1.2 million IU (children: 50000IU/kg; maximum 1.2 million IU) i.m. every 24 hours for 7 days or benzathine benzylpenicillin 1.2 million IU for adults and children >30kg (children £30kg: 30000IU/kg; maximum 600000IU) i.m. in a single dose or erythromycin 500mg (children: 10–15mg/kg; maximum 500mg) orally every 6 hours for 7 days.

Comments Vaccination with diphtheria–pertussis–tetanus (DPT) should be offered during convalescence.

19 Lower respiratory tract infections

Bronchitis Acute bronchitis In persons with a normal respiratory tract, acute infections of the trachea and bronchi are almost always viral in origin, although occasionally they may be caused by Mycoplasma pneumoniae. Fever and cough without cyanosis, chest indraw- ing, wheezing and rapid breathing are the main symptoms. If wheezing is present it is often due to asthma or bronchiolitis, in which case treatment is the same as for a viral infection of the respiratory tract and does not include antimicrobials.

Treatment Amoxicillin 500mg (children: 15mg/kg; maximum 500mg) orally every 8 hours for 5 days or doxycycline 100mg (children >8 years: 2mg/kg; maximum 100mg) orally every 12 hours for 5 days (contraindicated during pregnancy) or sulfamethoxazole 800mg + trimethoprim 160mg (children: 20mg/kg + 4mg/kg; maximum 800mg + 160mg) orally every 12 hours for 5 days.

Comments Cefalosporins and fluoroquinolones are not recommended for bronchitis. Acute exacerbations of chronic bronchitis Acute exacerbations of chronic bronchitis are often due to viral infection and do not require treatment with antimicrobials. Antimicrobial treatment should, however, be considered in patients with increasing cough, dyspnoea and increased pro- duction and purulence of sputum. The most common causa- tive organisms are H. influenzae, Moraxella catarrhalis and S. pneumoniae.

20 Lower respiratory tract infections

Doses refer to adults, as this condition is rarely found in children.

Treatment Amoxicillin 500mg orally every 8 hours for 5 days or amoxicillin 500mg + clavulanic acid orally every 8 hours for 5 days or sulfamethoxazole 800mg + trimethoprim 160mg orally every 12–24 hours for 5 days.

Comments Chronic purulent bronchial infection and chronic airway dis- ease are predominantly diseases of adults. Chronic suppurative lung disease in children (e.g. bronchiectasis) may occasionally require treatment with amoxicillin (30mg/kg (maximum 1g) orally every 8 hours for 5 days) or chloramphenicol (25mg/kg (maximum 1g) i.v. or i.m. every 6 hours for 5 days). Cystic fibrosis infections require specialist clinical management and laboratory services. Chronic recurrent cough Chronic cough is a common condition in adults and children associated with causes such as pollution, allergy, and passive and active smoking. Antimicrobials are not required. The occurrence of a chronic cough with persistent fever and weight loss should raise clinical suspicion of tuberculosis or bronchial cancer. Pneumonia The major symptoms of pneumonia are rapid breathing with cough. The respiratory rates above which pneumonia should be suspected are shown in the table overleaf.

In severe cases indrawing of the chest and cyanosis may also occur. Other symptoms and signs of pneumonia include pleural pain, fever and crepitations. Extrapulmonary features such as confusion or disorientation may predominate, and may

21 WHO Model Prescribing Information — Drugs used in bacterial infections

Cut-off points for rapid breathing

Age group Cut-off point for rapid breathing (no. of breaths/min)

0–2 months 60 2–12 months 50 12–60 months 40 Adults and children > 5 years 30

be the only signs in the elderly, immunosuppressed patients and malnourished children. The etiology of pneumonia varies greatly with the age and geographical location of the patient. Pneumonia in adults and children aged over 5 years The most important pathogen in this age group is Streptococcus pneumoniae, followed by atypical bacteria such as Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella spp. and Coxiella burnetti. Options for treatment of these infections have been considered by expert committees in many countries. The rec- ommendations of these committees are based on the prevalence of resistance of S. pneumoniae to macrolides and to penicillins, and on the prevalence of resistance of atypical pathogens to b- lactam antimicrobials. Patients with severe pneumonia should be admitted to hospital.

Groups at particular risk include those with pre-existing lung or heart disease, renal failure, diabetes, malnutrition or HIV infection, those who are dependent on alcohol, and the elderly. Clinical presentation and Gram-staining of sputum may aid in the diagnosis of the etiological pathogen(s).

Treatment Ambulatory patients Amoxicillin 500mg (children: 15mg/kg; maximum 500mg) orally every 8 hours for 5 days or erythromycin 500mg (children: 10–15mg/kg; maximum 500mg) orally every 6 hours for 5 days (14 days in cases of atypical pneumonia)

22 Lower respiratory tract infections or doxycycline 100mg (children >8 years: 2mg/kg; maximum 100mg) orally every 12 hours for 7–10 days (contraindicated during pregnancy) or sulfamethoxazole 800mg + trimethoprim 160mg (children: 20mg/kg + 4mg/kg; maximum 800mg + 160mg) orally every 12 hours for 5 days.

Hospitalized patients Benzylpenicillin 2 million IU (children: 50000–100000IU/kg; maximum 2 million IU) i.v. or i.m. every 4–6 hours for 5 days or chloramphenicol 1g (children: 25mg/kg; maximum 750mg) i.v. every 6 hours for 7 days or cefuroxime 1.0–1.5g (children: 50–60mg/kg; maximum 1.5g) i.v. every 6–8 hours for 7 days or ceftriaxone 1g (children: 50mg/kg; maximum 1g) i.v. or i.m. every 12–24 hours for 7 days.

Alternative regimen. Benzylpenicillin 2 million IU (children: 50000–100000IU/kg; maximum 2 million IU) i.v. or i.m. every 4–6 hours for 7 days plus gentamicin 5–7mg/kg i.v. daily in divided doses (children: 7.5mg/kg i.v. in 1–3 divided doses daily) for 7 days (con- traindicated during pregnancy).

In cases of atypical pneumonia, treatment is as described above, with the addition of erythromycin 1g (children: 10mg/kg; maximum 1g) i.v. every 6 hours for 14 days.

Pneumonia due to Staphylococcus aureus Treatment is as described on pages 28–29.

23 WHO Model Prescribing Information — Drugs used in bacterial infections

Comments Benzylpenicillin may be used alone when Streptococcus pneumoniae is the suspected pathogen.

In regions where the prevalence of resistance of S. pneumoniae to penicillins is high, consideration should be given to increas- ing the dose of amoxicillin. Erythromycin should be used only in regions where the prevalence of resistance of S. pneumoniae to the drug is low.

Gentamicin is not recommended for patients with significant renal failure (creatinine clearance <20ml/min). If gentamicin is used, close monitoring of serum concentrations is mandatory. Pneumonia in children aged from 2 months to 5 years In developing countries pneumonia in children aged from 2 months to 5 years is usually due to Streptococcus pneumoniae or Haemophilus influenzae or occasionally Staphylococcus aureus. In developed countries the disease is more likely to be of viral origin (respiratory syncytial virus or parainfluenza virus). However, in most cases an etiological pathogen is not identi- fied and as a result, empirical antimicrobial therapy for pneumonia is the commonly accepted practice worldwide.1 Pneumonia due to Staphylococcus aureus should be suspected if there is clinical deterioration despite treatment with chloram- phenicol or other normally appropriate antimicrobials, or in the presence of pneumatocoele or empyema.

Treatment Very severe pneumonia Procaine benzylpenicillin 50000IU/kg (maximum 900000IU) i.m. every 24 hours for at least 5 days or benzylpenicillin 50000–100000IU/kg (maximum 2 million IU) i.v. or i.m. every 4–6 hours for at least 5 days

1 For further information, see Acute respiratory infections in children: case management in small hospitals in developing countries. Geneva, World Health Organization, 1990 (unpub- lished document WHO/ARI/90.5; available on request from Child and Adolescent Health and Development, World Health Organization, 1211 Geneva 27, Switzerland).

24 Lower respiratory tract infections

or chloramphenicol 25mg/kg (maximum 750mg) i.v. or i.m. every 6 hours for at least 10 days (once clinical improvement occurs, oral dosage forms may be substituted) or ceftriaxone 50mg/kg (maximum 1g) i.v. or i.m. every 24 hours for at least 5 days.

Severe pneumonia Benzylpenicillin 50000–100000IU/kg (maximum 2 million IU) i.v. or i.m. every 4–6 hours for at least 5 days.

Mild pneumonia Amoxicillin 15–25mg/kg (maximum 500mg) orally every 8 hours for 5 days or sulfamethoxazole 20mg/kg + trimethoprim 4mg/kg (maxi- mum 800mg + 160mg) orally every 12 hours for 5 days or procaine benzylpenicillin 50000IU/kg (maximum 900000IU) i.m. every 24 hours for at least 3 days (once clinical improve- ment occurs, amoxicillin 15–25mg/kg (maximum 500mg) orally every 8 hours may be used to complete the treatment course of at least 5 days).

Pneumonia due to Staphylococcus aureus Treatment is as described on page 29. Pneumonia in neonates (aged up to 2 months) In neonates not all respiratory distress is due to infection. However, as pneumonia may be rapidly fatal in this age group, suspected cases should be treated promptly and referred to hospital for parenteral treatment with antimicrobials. The most likely pathogens are Streptococcus pneumoniae, group B streptococci, Escherichia coli, Enterobacteriaceae and Chlamydia trachomatis. Severe cases may be caused by Staphylococcus aureus.

25 WHO Model Prescribing Information — Drugs used in bacterial infections

Treatment Neonates should be treated for at least 5 days with continua- tion of therapy for 3 days after the child is well. If meningitis is suspected, treatment should be given for at least 14 days. In premature babies, the doses recommended here may need to be reduced.

Amoxicillin 30mg/kg i.v. every 12 hours for at least 5 days plus gentamicin 2.5mg/kg i.v. every 8 hours (neonates <7 days: 2.5mg/kg i.v. every 12 hours) for a total of at least 5 days.

Alternative regimens. Cefotaxime 50mg/kg i.v. every 12 hours for at least 5 days or chloramphenicol 25mg/kg (maximum 750mg) i.v. every 12 hours for at least 5 days (contraindicated in premature infants or neonates <7 days).

Comments Cefotaxime is preferred to ceftriaxone for this age group. It is often administered in combination with ampicillin (50mg/kg i.v. every 8 hours for at least 5 days), because of problems of resistance in Gram-negative enteric bacteria and the possibility of Listeria spp. infections in neonates.

Chloramphenicol should only be used when no alternatives are available, as it may cause the grey baby syndrome. Legionellosis Legionellosis, caused by Legionella pneumophila, is a water- borne infection spread by aerosolization. It mainly occurs in elderly persons with chronic obstructive airway disease, but may also occur in young, otherwise healthy, patients. It usually presents as severe pneumonia, often associated with non- pulmonary symptoms such as mental confusion, diarrhoea and renal failure. The diagnosis may be suggested by the presence of purulent sputum without pathogens visible on Gram-staining, and/or failure to respond to treatment with b-lactam antimicrobials.

26 Lower respiratory tract infections

Treatment Erythromycin 1g (children: 10mg/kg; maximum 500mg) i.v. every 6 hours for 10 days (once clinical improvement occurs, erythromycin 500mg (children: 7.5mg/kg; maximum 500mg) orally every 6 hours may be substituted) or ciprofloxacin 750mg orally every 12 hours for 10 days (con- traindicated during pregnancy; not approved for this indica- tion in children). Pneumonia associated with HIV infection Pneumocystis carinii is the most frequent pathogen, although in some areas, tuberculosis is more common. Other potential pathogens include Candida albicans, Aspergillus fumigatus and cytomegalovirus.

Doses refer to adults, as this condition is rarely observed in children.

Treatment for pneumonia due to Pneumocystis carinii Sulfamethoxazole 75mg/kg + trimethoprim 15mg/kg i.v. or orally every 6–8 hours for 21 days.

Alternative regimen. Clindamycin 600mg i.v. or orally every 6 hours for 21 days plus primaquine 15mg orally every 6 hours for 21 days. Aspiration pneumonia and lung abscesses Aspiration pneumonia and lung abscesses are most fre- quently caused by penicillin-sensitive anaerobic bacteria such as Peptostreptococcus spp., as well as aerobic bacteria such as Streptococcus pyogenes and viridans streptococci. Sometimes penicillin-resistant pathogens such as Bacteroides fragilis, Escherichia coli and Klebsiella pneumoniae may be involved. Pre- disposing factors include impaired consciousness, bronchial obstruction, alcohol dependence, cerebrovascular accidents and intestinal obstruction.

27 WHO Model Prescribing Information — Drugs used in bacterial infections

Treatment Benzylpenicillin 1–2 million IU (children: 50000–100000IU/kg; maximum 2 million IU) i.v. or i.m. every 4–6 hours for 10–14 days plus metronidazole 500mg (children: 12.5mg/kg; maximum 500mg) i.v. every 8–12 hours for 10–14 days (once clinical improvement occurs, metronidazole 400mg (children: 10mg/kg; maximum 400mg) orally every 12 hours may be substituted; contraindicated during pregnancy).

Alternative regimen. Amoxicillin 500mg + clavulanic acid (children: 15mg/kg; maximum 500mg) orally every 8 hours for 14 days or clindamycin 600mg i.v. every 8 hours (children: 10mg/kg; maximum 450mg i.v. or i.m. every 6 hours) for 14 days (once clinical improvement occurs, clindamycin 300–450mg (chil- dren: 5–10mg/kg; maximum 450mg) orally every 6–8 hours may be substituted). Pneumonia due to Staphylococcus aureus This form of pneumonia is especially common following a recent influenza infection.

Treatment Adults and children > 5 years Cloxacillin 1–2g (children >5 years: 50mg/kg; maximum 2g) i.v. or i.m. every 6 hours for 10–14 days or cefazolin 1–2g (children >5 years: 15–25mg/kg; maximum 2g) i.v. or i.m. every 8 hours for 10–14 days or clindamycin 600mg i.v. every 8 hours (children >5 years: 10mg/kg; maximum 450mg i.v. or i.m. every 6 hours) for 10– 14 days (once clinical improvement occurs, clindamycin 300– 450mg (children >5 years: 5–10mg/kg; maximum 450mg) orally every 6–8 hours may be substituted)

28 Lower respiratory tract infections

or vancomycin 1g (children >5 years: 20mg/kg; maximum 1g) i.v. every 12 hours for 10–14 days.

Children aged from 2 months to 5 years Cloxacillin 25–50mg/kg (maximum 2g) orally every 6 hours for at least 3 weeks plus gentamicin 7.5mg/kg i.v. in 1–3 divided doses daily for at least 3 weeks (contraindicated during pregnancy).

Comments Vancomycin should only be used if the pathogen is proven to be meticillin-resistant Staphylococcus aureus (MRSA). Empyema Empyema may complicate some bacterial pneumonias and requires prompt needle aspiration for bacterial diagnosis and surgical drainage. Prolonged treatment based on the results of Gram-staining and culture is often required. Nosocomial pneumonia Nosocomial pneumonia is pneumonia that is acquired in hos- pital 48 hours or more after admission. The responsible pathogens vary, depending on the hospital and country. Local information on the identification and susceptibility of common pathogens is therefore essential in devising initial therapy for such episodes. Multiresistant bacteria such as staphylococci, enterococci, enterobacteria, Pseudomonas aeruginosa and other aerobic bacteria may be responsible for such infections. Hospital-acquired legionellosis has also been described. Com- mon sources of nosocomial infections include: • Infected intravenous devices: Gram-positive bacteria, especially staphylococci. • Indwelling urinary catheters: Gram-negative bacteria. • Tracheostomy and ventilators: mixed bacterial flora. • Post-surgical wound infections: variable — depends on the operation site.

29 WHO Model Prescribing Information — Drugs used in bacterial infections

Treatment The recommendations for initial therapy vary, depending on the epidemiology and susceptibility of local pathogens. Antimicrobials with activity against Gram-positive and Gram-negative bacterial pathogens should be used. Suitable combinations include, for example: cloxacillin 1–2g (children: 50mg/kg; maximum 2g) i.v. every 6 hours for 7 days plus gentamicin 5–7mg/kg i.v. daily in divided doses (children: 7.5mg/kg i.v. in 1–3 divided doses daily) for 7 days (con- traindicated during pregnancy).

Alternative regimens. Ceftazidime 1g (children: 25mg/kg; maximum 1g) i.v. every 8 hours for 7 days plus either gentamicin 5–7mg/kg i.v. daily in divided doses (children: 7.5mg/kg i.v. in 1–3 divided doses daily) for 7 days (con- traindicated during pregnancy) or ciprofloxacin 500mg (children: 10mg/kg; maximum 300mg) i.v. every 12 hours for 7 days (contraindicated during pregnancy).

Comments In hospitals with a high prevalence of meticillin-resistant Staphylococcus aureus (MRSA), vancomycin 1g (children: 20mg/kg; maximum 1g) i.v. every 12 hours for 10–14 days should be added to the above regimens.

Imipenem 1–2g + cilastatin in 3–4 divided doses (children: 60mg/kg (maximum 2g) in 4 divided doses) daily by i.v. infu- sion until at least 2 days after resolution of signs and symptoms of infection should be reserved for the treatment of infections resistant to all other drugs on WHO’s Model List of Essential Drugs.

30 Other respiratory tract infections

Pertussis (whooping cough) Pertussis (whooping cough) is characterized by a paroxysmal cough which consists of a deep inspiration, followed by a series of short coughs which end in a whooping sound.

Administration of erythromycin 50mg/kg (maximum 2g) orally in 4 divided doses daily for 14 days, initiated early in the coryzal phase of the disease, may shorten the course of the illness, which otherwise may last for weeks or months. However, diagnosis at this early stage is often difficult. Once the paroxysmal phase of the disease is reached, antimicro- bial treatment is of no benefit except to eradicate any secondary pulmonary infection. Treatment with erythromycin eradicates the causative pathogen Bordetella pertussis from the nasopharynx, making the patient non-infectious to others; however, this is usually the only benefit of therapy. An effec- tive vaccine is available to prevent infection. Ornithosis The causative organism of ornithosis (psittacosis) is Chlamydia psittaci, which is shed by birds (especially psittacine birds) that carry the infectious agent. The disease is transmitted to humans through contact with infected birds.

Treatment Adults and children > 8 years Doxycycline 100mg (children >8 years: 2mg/kg; maximum 100mg) orally every 12 hours for 7–10 days (contraindicated during pregnancy).

Children £ 8 years of age Erythromycin 10–15mg/kg (maximum 500mg) orally every 6 hours for 7–10 days. Melioidosis Meliodosis, caused by a free-living soil bacillus Burkholderia pseudomallei, occurs in south-east Asia and northern Australia.

31 WHO Model Prescribing Information — Drugs used in bacterial infections

It presents most commonly as severe pneumonia and/or sep- ticaemia and has a high mortality.

Treatment Ceftazidime 2g (children: 50mg/kg; maximum 2g) i.v. every 8 hours for at least 14 days plus either sulfamethoxazole 1600mg + trimethoprim 320mg (children: 40mg/kg + 8mg/kg; maximum 1600mg + 320mg) orally or i.v. every 12 hours for at least 14 days or doxycycline 100mg (children >8 years: 2mg/kg; maximum 100mg) orally or i.v. every 12 hours for at least 14 days (con- traindicated during pregnancy).

Comments Prolonged i.v. therapy is necessary for deep-seated infections, osteomyelitis and septic arthritis. After the initial intensive therapy, eradication of any secondary infection is recom- mended with oral sulfamethoxazole + trimethoprim or doxy- cycline for at least 3 months.

32 Perioral and dental infections

Generally, the causative organisms of oral and dental infections are mixed anaerobic and aerobic oral flora. Gingival infections and periodontitis In the absence of systemic signs and symptoms, antimicrobial therapy is not usually indicated for gingival infections and periodontitis. Local dental care to control bacterial plaque is necessary. Antimicrobial therapy should be considered if infec- tion is accompanied by systemic signs or symptoms.

Treatment Procaine benzylpenicillin 1 million IU (children: 50000IU/kg; maximum 1 million IU) i.m. every 24 hours for 5 days or phenoxymethylpenicillin 500mg (children: 10–20mg/kg; maxi- mum 500mg) orally every 6 hours for 5 days or metronidazole 400–500mg (children: 10–12.5mg/kg; maxi- mum 250mg) orally every 12 hours for 5 days (contraindicated during pregnancy) or erythromycin 250mg (children: 7.5mg/kg; maximum 250mg) orally every 6 hours for 5 days. Tooth abscesses and suppurative odontogenic infections In the absence of systemic signs or symptoms, antimicrobial therapy is not usually indicated for tooth abscesses and sup- purative odontogenic infections. In pericoronitis warm mouth rinses with saline or chlorhexidine, 0.2% solution, and a topical paint (e.g. polyvidone–iodine) are of benefit. Dental abscesses may require extraction of the infected tooth. Antimicrobial therapy should be considered if infection is accompanied by systemic signs or symptoms.

33 WHO Model Prescribing Information — Drugs used in bacterial infections

Treatment Procaine benzylpenicillin 1 million IU (children: 50000IU/kg; maximum 1 million IU) i.m. every 24 hours for 3 days or phenoxymethylpenicillin 500mg (children: 10–20mg/kg; maxi- mum 500mg) orally every 6 hours for 3 days or amoxicillin 250mg (children: 25mg/kg; maximum 250mg) orally every 8 hours for 3 days. Acute cervical adenitis In young children (<5 years), acute adenitis may be due to a variety of both infectious and non-infectious causes. Acute bilateral cervical adenitis is most commonly caused by Streptococcus pyogenes. The recommended treatment is the same as for acute pharyngitis (see pages 14–15), although children who are severely ill may require treatment with procaine benzylpenicillin 50000 IU (maximum 1 million IU) i.m. every 24 hours for at least 10 days.

Acute adenitis at other sites in young children usually involves Staphylococcus aureus as well as Streptococcus pyogenes. In older children and adults, a wide range of other pathogens may also cause cervical adenitis, such as Corynebacterium diphtheriae, Mycobacterium tuberculosis, Brucella spp. and atypical mycobac- teria. Initial empirical therapy, however, should be with an agent that is bactericidal against both staphylococci and strep- tococci (e.g. cefalexin). Erythromycin may be used for the treat- ment of patients who are allergic to penicillins. The dosage and duration of treatment are the same as for acute pharyngitis (see pages 14–15).

34 Gastrointestinal tract infections

Diarrhoeal disease Three clinical presentations of diarrhoeal disease may require treatment with antimicrobials: acute watery diarrhoea, invasive diarrhoea (dysentery) and persistent diarrhoea. Acute watery diarrhoea Most cases of acute watery diarrhoea are caused by rotavirus and do not require treatment with antimicrobials. Antimicro- bial treatment is indicated, however, in cases due to infection with Vibrio cholerae. All cases of watery diarrhoea require mea- sures for the prevention and treatment of dehydration. Ade- quate nutrition should be maintained.

Cholera Cholera is caused by Vibrio cholerae and is characterized by severe acute watery diarrhoea. Several litres of fluid may be lost within a few hours, causing severe dehydration. Cholera occurs in endemic and epidemic situations. The antimicrobial sus- ceptibility of the local strains must be determined and multiple isolates tested during the course of an outbreak to confirm susceptibility.

It is now recognized that as many as 90% of patients with cholera require no more treatment than prompt and adequate oral replacement of the water and electrolytes lost in the diar- rhoeal stool and vomitus. Those who are severely dehydrated require intravenous fluids and antimicrobials.

Treatment Doxycycline 300mg (children >8 years: 2mg/kg; maximum 100mg) orally in a single dose (contraindicated during pregnancy) or ciprofloxacin 1g (children: 20mg/kg; maximum 1g) orally in a single dose (contraindicated during pregnancy).

35 WHO Model Prescribing Information — Drugs used in bacterial infections

Invasive diarrhoea (dysentery) In developing countries invasive diarrhoea or dysentery is often due to Shigella spp., with less severe diarrhoea caused by Campylobacter spp. In some countries enteroinvasive Escherichia coli is also common.

Shigellosis The susceptibility of Shigella spp. varies between countries, with multiresistant strains encountered in many regions. Therapy should initially be based on data on the susceptibi- lity of local strains and modified once the results of stool cul- ture and susceptibility tests are known. Neonates with bloody diarrhoea should be referred to hospital for treatment.

Treatment Nalidixic acid 1g (children ≥3 months: 15mg/kg; maximum 1g) orally every 6 hours for 5 days (contraindicated during pregnancy) or ciprofloxacin 1g (children: 20mg/kg; maximum 1g) orally in a single dose (contraindicated during pregnancy).

Comments Patients with infection due to Shigella dysenteriae serotype 1 should receive ciprofloxacin 500mg (children: 10mg/kg; maxi- mum 500mg) orally every 12 hours for 5 days (contraindicated during pregnancy).

Ciprofloxacin is the preferred treatment option in all cases, but because of its lower cost, nalidixic acid is used in some countries. It should be noted, however, that the use of nalidixic acid may result in reduced susceptibility of Shigella spp. to ciprofloxacin.

Enteritis due to Campylobacter jejuni Many patients with enteritis due to Campylobacter jejuni are asymptomatic by the time the diagnosis has been established and therefore do not require treatment with antimicrobials. Treatment should only be considered for patients with persis- tent symptoms.

36 Gastrointestinal tract infections

Treatment Erythromycin 500mg (children: 10mg/kg; maximum 500mg) orally every 6 hours for 7–10 days or ciprofloxacin 500mg orally every 12 hours for 7–10 days (con- traindicated during pregnancy).

Comments Ciprofloxacin is not licensed for use in children for enteritis due to Campylobacter jejuni, but is frequently used, particularly in patients with fever and/or bloody stools. Some ciprofloxacin- resistant strains have been noted.

Diarrhoea due to enteroinvasive Escherichia coli Antimicrobials are generally not required for the treatment of diarrhoea due to enteroinvasive Escherichia coli. Furthermore, there is some evidence to suggest that such treatment may worsen the disease. Persistent diarrhoea In general, routine treatment of persistent diarrhoea with antimicrobials is not effective and is not recommended. How- ever, children with persistent diarrhoea caused by shigellosis, amoebiasis or giardiasis, or with associated non-intestinal infections, such as pneumonia, sepsis, upper respiratory tract infections or otitis media may require antimicrobials. Such treatment should follow standard guidelines.1

Severely malnourished children should receive broad- spectrum antimicrobials for several days when admitted to hospital.2

Persistent diarrhoea may also be associated with HIV infection. In this situation, pathogens may include Salmonella, Crypto- sporidium or Microsporidium spp.

1 See The treatment of diarrhoea: a manual for physicians and other senior health workers, 3rd rev. Geneva, World Health Organization, 1995 (unpublished document WHO/CDR/95.3; avail- able from Communicable Diseases: Control, Prevention and Eradication, World Health Or- ganization, 1211 Geneva 27, Switzerland). 2 See Management of severe malnutrition — a manual for physicians and other senior health workers. Geneva, World Health Organization, 1999.

37 WHO Model Prescribing Information — Drugs used in bacterial infections

Acute enteric infections Typhoid and paratyphoid fever Typhoid and paratyphoid fever are caused, respectively, by the pathogens Salmonella typhi and S. paratyphi, which are spe- cific to humans. Transmission occurs via contaminated water and/or food. Following treatment with antimicrobials, about 10% of patients relapse and 1–3% become chronic carriers of infection.

Treatment Chloramphenicol 1g (children 25mg/kg; maximum 750mg) orally every 6 hours for 10–14 days or ciprofloxacin 500–750mg (children 10–15mg/kg; maximum 500mg) orally every 12 hours for 5–14 days (contraindicated during pregnancy) or sulfamethoxazole 800mg + trimethoprim 160mg (children: 20mg/kg + 4mg/kg; maximum 800mg + 160mg) orally every 12 hours for 3 days.

Chronic carriers Ciprofloxacin 500–750mg orally every 12 hours for 4–6 weeks (contraindicated during pregnancy; children: ampicillin 10mg/kg (maximum 250mg) i.m. every 6 hours for 4–6 weeks).

Comments In many developing countries chloramphenicol is preferred, due to its lower cost. However, the prevalence of resistance to the drug is increasing. Ciprofloxacin is not licensed for either of these indications in children, but is frequently used in short courses. Chloramphenicol and ampicillin appear to be less ef- fective than ciprofloxacin in treating chronic carriers of infec- tion. However, prolonged use of ciprofloxacin in children should be avoided. Infectious enteritis due to Salmonella spp. other than S. typhi In infectious enteritis due to Salmonella enteritidis, treatment is the same as that recommended for typhoid fever (see above). In other circumstances antimicrobial therapy is not

38 Gastrointestinal tract infections

recommended. However, chronic bacteraemia, metastatic infec- tions or enterocolitis in patients with sickle-cell disease, HIV infection or other predisposing conditions must be treated.

In developing countries multiresistant salmonella infections (including septicaemia) may be nosocomial in origin, especially among children. Recommendations for antimicrobial therapy should be based on data on the susceptibility of local strains. Enteritis due to enterotoxigenic Escherichia coli Chemoprophylaxis against so-called “traveller’s diarrhoea” is not indicated. Mild cases require no treatment. However, antimicrobial therapy should be considered if diarrhoea persists or is severe (e.g. more than five bowel movements per day, bloody diarrhoea and/or fever).

Treatment Sulfamethoxazole 800mg + trimethoprim 160mg (children: 20mg/kg + 4mg/kg; maximum 800mg + 160mg) orally every 12 hours for 3 days or ciprofloxacin 500mg (children: 10mg/kg; maximum 500mg) orally every 12 hours for 3 days (contraindicated during pregnancy).

Comments Tetracycline, doxycycline, chloramphenicol and cefalosporins are not recommended. Ciprofloxacin is not licensed for use in children for this indication, but may be used for short courses if there are no suitable alternatives. Intestinal protozoal infections Amoebiasis Amoebiasis is an uncommon form of bloody diarrhoea due to the protozoan Entamoeba histolytica. The diagnosis should be considered if a patient has persistent bloody diarrhoea (dysen- tery) despite therapy for shigellosis. Only certain strains of E. histolytica are pathogenic and asymptomatic carriers are common in endemic areas. Patients with invasive disease require consecutive treatment with a systemically active amoe- bicide followed by a luminal amoebicide in order to eliminate any surviving organisms in the colon. Clearance of cysts in the

39 WHO Model Prescribing Information — Drugs used in bacterial infections

faeces should be mainly considered in patients living in non- endemic areas.

Treatment Metronidazole 10mg/kg (maximum 250mg) orally every 8 hours for 8–10 days (adults and children; contraindicated during pregnancy) followed by diloxanide furoate 500mg (children: 6–7mg/kg; maximum 500mg) orally every 8 hours for 10 days.

Giardiasis Giardia lamblia is a flagellated protozoan which is transmitted from person to person mainly via faecal contamination of food or hands. It occurs worldwide, particularly where sanitation is poor, and is a common cause of both acute and persistent diar- rhoea among children in developing countries.

Treatment Metronidazole 2g (children: 30mg/kg; maximum 1.2g) orally every 24 hours for 3 days (contraindicated during pregnancy) or tinidazole 2g (children: 50mg/kg; maximum 2g) orally in a single dose (contraindicated during pregnancy). Necrotizing enterocolitis due to Clostridium difficile This is a form of pseudomembranous enterocolitis caused by toxigenic Clostridium difficile, following alteration of the intesti- nal microflora. Previous use of antimicrobials, especially am- picillin, cefalosporins and clindamycin, is often implicated. Treatment with any suspect antimicrobial should be ceased immediately. If toxigenic C. difficile is proven or suspected, treatment should be initiated promptly.

Treatment Metronidazole 200mg (children: 12.5mg/kg; maximum 200mg) orally every 8 hours for 7–14 days (contraindicated during pregnancy).

Comments Patients who fail to respond to treatment with metronidazole should receive vancomycin 125mg (children: 5mg/kg; maxi- mum 125mg) orally every 6 hours for 7–14 days. 40 Gastrointestinal tract infections

Non-diarrhoeal gastrointestinal infections Acute gastritis and peptic ulcer disease Acute gastritis and peptic ulcer disease are commonly associ- ated with infection of the mucosa of the upper gastrointestinal tract with Helicobacter pylori. If possible, presence of the organ- ism should be confirmed by biopsy (for bacterial culture) or by a positive breath test (for ketones). Various treatment regimens have been used, of which the following options are suggested based on their efficacy, simplicity and availability. Only adult doses are described, as the condition is not usually found in children. Both regimens are associated with a 80–85% clearance rate.

Treatment Bismuth salicylate 107.7mg (1 tablet) orally every 6 hours for 2 weeks plus metronidazole 200mg orally every 8 hours and 400mg orally at night for 2 weeks (contraindicated during pregnancy) plus either tetracycline 500mg orally every 6 hours for 2 weeks (con- traindicated during pregnancy) or amoxicillin 500mg orally every 6 hours for 2 weeks.

Alternative regimen. Omeprazole 40mg orally every 24 hours for 2 weeks plus metronidazole 400mg orally every 8 hours for 2 weeks (con- traindicated during pregnancy) plus amoxicillin 500mg orally every 8 hours for 2 weeks. Acute cholecystitis Acute cholecystitis is often associated with obstruction by calculi. The infecting organisms are predominantly ascending bowel flora, especially Escherichia coli and Klebsiella spp. Sudden onset of pyrexia, often with rigors, and pain and

41 WHO Model Prescribing Information — Drugs used in bacterial infections

tenderness in the right upper quadrant are characteristic. Jaundice is often an accompanying sign. Immediate surgery is required for gangrenous cholecystitis, associated perforation and abscess formation.

Treatment Ampicillin 1–2g (children: 25–50mg/kg; maximum 2g) i.v. or i.m. every 6 hours for up to 7 days plus gentamicin 5–7mg/kg i.v. daily in divided doses (children: 7.5mg/kg i.v. in 1–3 divided doses daily) for up to 7 days (con- traindicated during pregnancy). Acute peritonitis Intra-abdominal sepsis may develop either as a result of an external injury (e.g. a stab wound), a ruptured intra-abdominal organ (e.g. appendicitis) or postoperatively following abdomi- nal or pelvic surgery. Typically, the involved pathogens are the patient’s own bowel flora (aerobes and anaerobes). Severe pain, vomiting and pyrexia are common. Other signs include rigid- ity, rebound tenderness and absent bowel sounds.

Treatment Ampicillin 2g (children: 50mg/kg; maximum 2g) i.v. or i.m. every 6 hours for at least 7 days plus gentamicin 5–7mg/kg i.v. daily in divided doses (children: 7.5mg/kg i.v. in 1–3 divided doses daily) for at least 7 days (contraindicated during pregnancy) plus metronidazole 500mg (children: 12.5mg/kg; maximum 500mg) i.v. every 8–12 hours for at least 7 days (contraindi- cated during pregnancy).

For patients who are allergic to penicillins, ampicillin should be deleted from the above regimen.

42 Urinary tract infections

Urinary tract infections in women Uncomplicated infections Acute cystitis is the most common clinical manifestation of an uncomplicated urinary tract infection, especially in young women. Most infections are caused by Escherichia coli, while Staphylococcus saprophyticus is a less common pathogen. In women who are not pregnant, diagnostic signs of an acute infection of the lower urinary tract include dysuria, urgency and frequency of micturition, pyuria and the presence of high numbers of bacteria in the urine (>105/ml).

Treatment Trimethoprim 300mg orally every 24 hours for 3 days or nitrofurantoin 100mg orally every 12 hours for 3 days or cefalexin 500mg orally every 8 hours for 5 days.

Comments Treatment of urinary tract infections during pregnancy should be based on the results of urine culture and antimicrobial sus- ceptibility testing; however, trimethoprim should be avoided. The majority of such patients should be considered for urinary tract investigation in the puerperium.

Fluoroquinolones (e.g. ciprofloxacin) and most cefalospo- rins should not be used to treat uncomplicated urinary tract infections. Complicated infections Complicated urinary tract infections are those associated with structural abnormalities of the urinary tract or calculi, recurrent infections, or infections in patients with underlying diseases such as diabetes. Culture and antimicrobial susceptibility data should be available to direct therapy because of the potentially

43 WHO Model Prescribing Information — Drugs used in bacterial infections

wide range of multiresistant pathogens. The range of anti- microbials suitable for therapy include those described above. Urinary tract infections in men Urinary tract infections occurring in men should not be regarded as uncomplicated. An underlying abnormality of the urinary tract is common and there is often associated infection of the posterior urethra, prostate or epididymis. All males with a urinary tract infection should be investigated to detect a pos- sible underlying abnormality. The treatment is the same as that recommended for acute cystitis in women, except that it should be continued for at least 14 days. The presence of underlying prostatitis, in particular, may require prolonged therapy with antimicrobials (see pages 45–46). Urinary tract infections in children When cystitis is confirmed by a positive urine culture, investi- gation is required to exclude an underlying abnormality of the urinary tract in boys of all ages, girls under 5 years and pre- menarcheal girls with recurrent urinary tract infections.

Fluoroquinolones, trimethoprim and most cefalosporins should be avoided in children unless deemed necessary on microbiological grounds.

Treatment Cefalexin 12.5mg/kg ( maximum 500mg) orally every 6 hours for 5–10 days or amoxicillin 7.5mg/kg + clavulanic acid (maximum 250mg) orally every 8 hours for 5–10 days.

Comments Prophylaxis with antimicrobials (e.g. nitrofurantoin 50mg orally at night) should be considered after cessation of the treat- ment course, until such time as urinary tract investigation and imaging have been completed.

44 Urinary tract infections

Acute pyelonephritis Bacterial infections of the renal parenchyma are usually due to the ascent of organisms via the ureter into the kidney. Most infections are due to Escherichia coli and some may be due to Proteus, Klebsiella or Enterococcus spp. Sudden onset of pain in one or both kidneys together with high fever and symptoms of infection of the lower urinary tract are characteristic. Rigors and vomiting may occur and occasionally septicaemic shock supervenes.

Treatment Ampicillin 1–2g (children: 50mg/kg; maximum 2g) i.v. or i.m. every 6 hours for up to 14 days plus either gentamicin 5–7mg/kg orally daily in divided doses (children: 7.5mg/kg orally in 1–3 divided doses daily) for 7 days (con- traindicated during pregnancy) or ceftriaxone 1g (children: 50mg/kg; maximum 1g) i.v. or i.m. every 24 hours for 14 days.

Comments Gentamicin should be avoided in patients with significant renal impairment. Some clinicians use ceftriaxone alone. Following an initial response (e.g. resolution of fever) and depending on the clinical circumstances, consideration of a change to an active oral agent (e.g. oral ciprofloxacin 750mg every 12 hours; contraindicated during pregnancy) to complete the treatment course may be appropriate. Prostatitis Acute prostatitis is characterized by symptoms of infection of the lower urinary tract, together with fever, pain in the perineal area and tenderness of the prostate. A number of pathogens may be responsible, including Escherichia coli and Staphylococ- cus aureus. In many cases no organism is identified. Most patients recover after treatment, but chronic prostatitis may develop which can be difficult to cure.

45 WHO Model Prescribing Information — Drugs used in bacterial infections

Doses refer to adults, as this condition is not found in children.

Treatment Trimethoprim 200mg orally every 12 hours for 4–6 weeks or ciprofloxacin 500mg orally every 12 hours for 4–6 weeks.

Comments Cases that fail to respond to treatment may be due to Chlamy- dia trachomatis or Ureaplasma urealyticum, and can be treated empirically with erythromycin 500mg orally every 6 hours for 14 days or doxycycline 100mg orally every 12 hours for 14 days.

46 Skin and soft tissue infections

Localized purulent skin lesions Localized purulent lesions of the skin such as furunculosis and folliculitis do not usually require therapy with systemic antimicrobials, except in patients who are immunosup- pressed, such as those with HIV infection or diabetes. However, more extensive lesions with collections of pus require drainage and antimicrobial treatment. The most frequent pathogens are staphylococci. The lesions should be covered with clean dressings.

Treatment Cloxacillin 250–500mg (children: 12.5–25mg/kg; maximum 500mg) orally every 6 hours for 5–7 days or cefalexin 500mg (children: 12.5–25mg/kg; maximum 500mg) orally every 6 hours for 5–7 days or sulfamethoxazole 800mg + trimethoprim 160mg (children: 20mg/kg + 4mg/kg; maximum 800mg + 160mg) orally every 12 hours for 5–7 days. Impetigo Impetigo is a highly contagious superficial purulent skin disease caused by staphylococci, streptococci, or a combination of both organisms. It is particularly common in infants and small children. Glomerulonephritis is a severe complication which may occur if the infecting pathogen is a nephritogenic strain of Streptococcus pyogenes. Antimicrobial therapy is ne- cessary in these cases to try to prevent transmission of the infection.

Treatment Cloxacillin 250–500mg (children: 12.5–25mg/kg; maximum 500mg) orally every 6 hours for 5–7 days

47 WHO Model Prescribing Information — Drugs used in bacterial infections

or cefalexin 500mg (children: 12.5–25mg/kg; maximum 500mg) orally every 6 hours for 5–7 days or sulfamethoxazole 800mg + trimethoprim 160mg (children: 20mg/kg + 4mg/kg; maximum 800mg + 160mg) orally every 12 hours for 5–7 days. Cellulitis and erysipelas Cellulitis and erysipelas are streptococcal infections of the subcutaneous tissues, which usually result from contamination of minor wounds. Both conditions are characterized by acute localized inflammation and oedema. The lesions are more superficial in erysipelas than in cellulitis and have a well defined, raised margin. Potentially fatal systemic toxaemia may supervene in patients who remain untreated. Recurrent celluli- tis or erysipelas can result in chronic lymphoedema which may, in turn, serve as a predisposing factor for recurrent episodes of infection.

In infants, facial lesions similar to those of cellulitis and erysipelas may be caused by Haemophilus influenzae; however, this condition is rare in countries where H. influenzae vaccina- tion programmes have been instituted.

Treatment Procaine benzylpenicillin 1.5 million IU (children: 50000IU/kg; maximum 1.5 million IU) i.m. every 24 hours for 7–10 days or benzylpenicillin 1–2 million IU (children: 50000–100000IU/kg; maximum 2 million IU) i.v. or i.m. every 6 hours for 7–10 days (once clinical improvement occurs, amoxicillin 500mg (chil- dren: 7.5–15mg/kg; maximum 500mg) orally every 8 hours may be substituted) or cefazolin 1–2g (children: 15mg/kg; maximum 2g) i.v. or i.m. every 8 hours for 7–10 days (once clinical improvement occurs, cefalexin 500mg (children: 12.5–25mg/kg; maximum 500mg) orally every 6 hours may be substituted).

48 Skin and soft tissue infections

Streptococcal necrotizing fasciitis Streptococcal necrotizing fasciitis is characterized by a fulmi- nant spreading subcutaneous necrosis that affects fascial tissue following minor trauma with infection due to group A b-haemolytic Streptococcus pyogenes. Diagnosis is by Gram- staining and culture of tissue fluid. Treatment consists primarily of surgical debridement of the necrotic tissue together with appropriate antimicrobial therapy.

Clinical differentiation between streptococcal fasciitis and so- called “synergistic gangrene” may be difficult; in such cases treatment should be the same as for gangrene (see below).

Treatment Benzylpenicillin 4 million IU (children: 100000IU/kg; maxi- mum 4 million IU) i.v. or i.m. every 4 hours for at least 7 days plus clindamycin 600mg i.v. every 8 hours (children: 10mg/kg; maximum 450mg i.v. every 6 hours) for at least 7 days. Gangrene Clostridial gangrene, following traumatic injuries of the limbs or surgical procedures, is characterized by rapidly spreading deep necrosis with gas in the tissue. A similar condition is “syn- ergistic gangrene”, which arises in the perineal area, generally following relatively minor trauma, and is associated with gradual sloughing of the skin and subcutaneous necrosis. Both conditions are caused by Clostridium spp., especially C. perfrin- gens and C. novyi. Large Gram-positive bacilli seen on Gram- staining of exudate are suggestive of clostridial sepsis, while a mixture of Gram-positive cocci and bacilli and Gram-negative bacilli is indicative of synergistic gangrene. In both conditions the basis of treatment is immediate surgical debridement and antimicrobial therapy.

Treatment Benzylpenicillin 4 million IU (children: 100000IU/kg; maximum 4 million IU) i.v. or i.m. every 4 hours for at least 7 days

49 WHO Model Prescribing Information — Drugs used in bacterial infections

plus gentamicin 5–7mg/kg i.v. or i.m. daily in divided doses (chil- dren: 7.5mg/kg i.v. or i.m. in 1–3 divided doses daily) for at least 7 days (contraindicated during pregnancy) plus metronidazole 500mg (children: 12.5mg/kg; maximum 500mg) i.v. every 8 hours for at least 7 days (once clinical improvement occurs, rectal formulations may be substituted; contraindicated during pregnancy).

For patients who are allergic to penicillins, benzylpenicillin should be replaced by clindamycin 600mg (children: 10mg/kg; maximum 450mg) orally or i.v. every 6–8 hours. Pyomyositis Pyomyositis is characterized by a deep-seated muscle abscess, most commonly due to Staphylococcus aureus. Although pyo- myositis may follow trauma, there may often be no obvious portal of entry, with infection due to haematogenous spread. Treatment includes drainage, identification of the pathogen (Gram-staining is usually diagnostic) and antimicrobial therapy.

Treatment Cloxacillin 2g (children: 25–50mg/kg; maximum 2g) i.v. or i.m. every 6 hours for 5–10 days (once clinical improvement occurs, cloxacillin 500mg (children: 12.5–25mg/kg; maximum 500mg) orally every 6 hours may be substituted) or cefazolin 1–2g (children: 15mg/kg; maximum 2g) i.v. or i.m. every 8 hours for 5–10 days (once clinical improvement occurs, cefalexin 500mg (children: 12.5–25mg/kg; maximum 500mg) orally every 6 hours may be substituted) or clindamycin 600mg i.v. every 8 hours (children: 10mg/kg; maximum 450mg i.v. every 6 hours) for 5–10 days (once clinical improvement occurs, clindamycin 300–450mg (chil- dren: 5–10mg/kg; maximum 450mg) orally every 4–6 hours may be substituted).

50 Skin and soft tissue infections

Contaminated soft tissue injuries Infections of the soft tissues frequently occur following crush injuries, stab wounds and related injuries, such as gunshot wounds. Such infections are usually caused by Staphylococcus aureus, Streptococcus pyogenes, anaerobic bacteria (especially Clostridium spp.) or aerobic Gram-negative bacteria.

Treatment Cloxacillin 2g (children: 25–50mg/kg; maximum 2g) i.v. or i.m. every 6 hours for 5–10 days (once clinical improvement occurs, cloxacillin 500mg (children: 12.5–25mg/kg; maximum 500mg) orally every 6 hours may be substituted) plus gentamicin 5–7mg/kg i.v. or i.m. daily in divided doses (chil- dren: 7.5mg/kg i.v. or i.m. in 1–3 divided doses daily) for 5–10 days (contraindicated during pregnancy) plus metronidazole 500mg (children: 12.5mg/kg; maximum 500mg) i.v. every 8 hours for 5–10 days (once clinical impro- vement occurs, oral or rectal formulations of metronidazole may be substituted; contraindicated during pregnancy). Human and animal bites and clenched-fist injuries Human and animal bites and clenched-fist (punching) injuries often become infected. Causative pathogens in human bites include Staphylococcus aureus, Streptococcus spp., Eikenella corro- dens and b-lactamase-producing anaerobic bacteria. In animal bites the most common causes are Pasteurella multocida, Staphy- lococcus aureus, Capnocytophaga canimorsus, Streptococcus spp. and anaerobic bacteria.

Treatment should include thorough cleaning, debridement and immobilization of the wound and prophylactic antimicrobials. If infection is suspected cultures should be taken. Wounds at a high risk of infection include: — wounds with delayed presentation (i.e. at least 8 hours); — puncture wounds unable to be adequately debrided;

51 WHO Model Prescribing Information — Drugs used in bacterial infections

— wounds on the hands, feet or face; — wounds with underlying structures involved; — wounds in immunocompromised patients. For wounds that fall into these categories and those that are moderate or severe in nature, presumptive treatment with antimicrobials should be considered.

Treatment Procaine benzylpenicillin 1.5 million IU (children: 50000IU/kg; maximum 1.5 million IU) i.m. every 24 hours for 5 days followed by amoxicillin 500mg + clavulanic acid (children: 15mg/kg; maximum 500mg) orally every 8 hours for 5 days.

Patients allergic to penicillins Metronidazole 400–500mg (children: 10–12.5mg/kg; maxi- mum 250mg) orally every 12 hours for 5–10 days (contraindi- cated during pregnancy) plus either doxycycline 100mg (children >8 years: 2mg/kg; maximum 100mg) orally every 24 hours for 5–10 days (contraindicated during pregnancy) or sulfamethoxazole 800mg + trimethoprim 160mg (children: 20mg/kg + 4mg/kg; maximum 800mg + 160mg) orally every 12 hours for 5–10 days.

Comments The choice of treatment will be determined by the organisms cultured from the infected wound. In all cases, consideration should be given to prophylaxis against tetanus. Animal bites may also require prophylaxis against rabies.

52 Bone and joint infections

Osteomyelitis Acute osteomyelitis arising in children and adults is usually caused by Staphylococcus aureus and less commonly b- haemolytic streptococci. In sickle-cell disease, osteomyelitis may be caused by Salmonella spp. Blood cultures and/or bone aspiration will help to establish an etiological diagnosis. Acute osteomyelitis generally requires treatment for 4–6 weeks, with most, if not all, therapy administered parenterally. Osteomyelitis in adults Treatment Osteomyelitis due to Staphylococcus aureus Cloxacillin 2g i.v. or i.m. every 6 hours for at least the initial 14 days, but preferably the entire treatment course of 4–6 weeks (if the duration of parenteral therapy is less than 4–6 weeks, the treatment course should be completed with cloxacillin 1g orally every 6 hours) or cefazolin 1–2g i.v. or i.m. every 8 hours for 4–6 weeks (if the duration of parenteral therapy is less than 4–6 weeks, the treat- ment course should be completed with cefalexin 1–2g orally every 6 hours) or clindamycin 600mg i.v. every 8 hours for 4–6 weeks (if the duration of parenteral therapy is less than 4–6 weeks, the treat- ment course should be completed with clindamycin 300–450mg orally every 6 hours).

Osteomyelitis due to b-haemolytic streptococci Benzylpenicillin 2 million IU (1.2g) i.v. or i.m. every 4–6 hours for 2–4 weeks (if the duration of parenteral therapy is less than 2–4 weeks, the treatment course should be completed with amoxicillin 1g orally every 6–8 hours).

53 WHO Model Prescribing Information — Drugs used in bacterial infections

Osteomyelitis due to Salmonella spp. Ciprofloxacin 750mg orally every 12 hours for 6 weeks (con- traindicated during pregnancy). Osteomyelitis in children aged over 5 years Osteomyelitis in children aged over 5 years is generally caused by Staphylococcus aureus. Treatment may include cloxacillin, which is reasonably well absorbed from the gastrointestinal tract in children, allowing a greater proportion of the total treat- ment regimen to be given orally than in adults.

Treatment Osteomyelitis due to Staphylococcus aureus Cloxacillin 25–50mg/kg (maximum 2g) i.v. or i.m. every 4–6 hours for 4–6 days (or until clinical improvement occurs), fol- lowed by cloxacillin 25mg/kg (maximum 500mg) orally every 6 hours to complete the treatment course of 3–4 weeks or ceftriaxone 50–75mg/kg (maximum 1g) i.v. or i.m. every 24 hours for 4–6 days (or until clinical improvement occurs), fol- lowed by cloxacillin 25mg/kg (maximum 500mg) or cefalexin 25mg/kg (maximum 500mg) orally every 6 hours to complete the treatment course of 3–4 weeks or cefazolin 15mg/kg (maximum 1g) i.v. or i.m. every 8 hours for 4–6 days (or until clinical improvement occurs), followed by cefalexin 25mg/kg (maximum 500mg) orally every 6 hours to complete the treatment course of 3–4 weeks or clindamycin 10mg/kg (maximum 450mg) i.v. every 6 hours for 4–6 days (or until clinical improvement occurs), followed by clindamycin 10mg/kg (maximum 450mg) orally every 6 hours to complete the treatment course of 3–4 weeks. Osteomyelitis in children aged up to 5 years Haemophilus influenzae is the most common cause of osteo- myelitis among children aged up to 5 years, especially among those not immunized against H. influenzae type b (Hib). The total duration of treatment is generally at least 3–4 weeks.

54 Bone and joint infections

Treatment Osteomyelitis due to Haemophilus influenzae or unknown pathogen Children aged from 2 months to 5 years. Cloxacillin 25–50mg/kg (maximum 2g) i.v. or i.m. every 4–6 hours for 4–6 days (or until clinical improvement occurs) plus ceftriaxone 50–75mg/kg (maximum 1g) i.v. or i.m. every 24 hours for 4–6 days (or until clinical improvement occurs) followed by amoxicillin 15mg/kg + clavulanic acid (maximum 500mg) orally every 8 hours to complete the treatment course of 3–4 weeks.

Neonates. Cloxacillin 25–50mg/kg (maximum 2g) i.v. or i.m. every 4–6 hours for 4–6 days (or until clinical improvement occurs) plus cefotaxime 50–75mg/kg (maximum 2g) i.v. every 8 hours for 4–6 days (or until clinical improvement occurs) followed by amoxicillin 15mg/kg + clavulanic acid (maximum 500mg) orally every 8 hours to complete the treatment course of 3–4 weeks.

Osteomyelitis due to Staphylococcus aureus Children aged from 2 months to 5 years. Cloxacillin 25–50mg/kg (maximum 2g) i.v. or i.m. every 4–6 hours for 4–6 days (or until clinical improvement occurs) plus ceftriaxone 50–75mg/kg (maximum 1g) i.v. or i.m. every 24 hours for 4–6 days (or until clinical improvement occurs) followed by cloxacillin 12.5mg/kg (maximum 500mg) orally every 6 hours to complete the treatment course of 3–4 weeks.

Neonates. Cloxacillin 25–50mg/kg (maximum 2g) i.v. or i.m. every 4–6 hours for 4–6 days (or until clinical improvement occurs)

55 WHO Model Prescribing Information — Drugs used in bacterial infections

plus cefotaxime 50–75mg/kg (maximum 2g) i.v. every 8 hours for 4–6 days (or until clinical improvement occurs) followed by cloxacillin 12.5mg/kg (maximum 500mg) orally every 6 hours to complete the treatment course of 3–4 weeks.

Osteomyelitis due to Salmonella spp. Children aged from 2 months to 5 years. Treatment options will depend on the susceptibility of the pathogen, but include the following: cloxacillin 25–50mg/kg (maximum 2g) i.v. or i.m. every 4–6 hours for 4–6 days (or until clinical improvement occurs) plus ceftriaxone 50–75mg/kg (maximum 1g) i.v. or i.m. every 24 hours for 4–6 days (or until clinical improvement occurs) followed by either sulfamethoxazole 20mg/kg + trimethoprim 4mg/kg (maxi- mum 800mg + 160mg) orally every 12 hours to complete the treatment course of 6 weeks or amoxicillin 7.5–15mg/kg (maximum 1g) orally every 8 hours to complete the treatment course of 6 weeks or ciprofloxacin 10–15mg/kg (maximum 500mg) orally every 12 hours to complete the treatment course of 6 weeks.

Neonates. Treatment options will depend on the susceptibility of the pathogen, but include the following: cloxacillin 25–50mg/kg (maximum 2g) i.v. or i.m. every 4–6 hours for 4–6 days (or until clinical improvement occurs) plus cefotaxime 50–75mg/kg (maximum 2g) i.v. every 8 hours for 4–6 days (or until clinical improvement occurs)

56 Bone and joint infections

followed by either sulfamethoxazole 20mg/kg + trimethoprim 4mg/kg (maxi- mum 800mg + 160mg) orally every 12 hours to complete the treatment course of 6 weeks or amoxicillin 7.5–15mg/kg (maximum 1g) orally every 8 hours to complete the treatment course of 6 weeks or ciprofloxacin 10–15mg/kg (maximum 500mg) orally every 12 hours to complete the treatment course of 6 weeks.

Comments If acute osteomyelitis is not cured, chronic osteomyelitis may develop. Treatment of the latter condition comprises surgical debridement of dead bone and necrotic tissue, accompanied by antimicrobial therapy directed against the infecting pathogen for 4–6 weeks. Where prosthetic materials (e.g. fixation screws or plates, or artificial joints) are associated with osteomyelitis, cure is extremely difficult without removal of the prosthetic device. Septic arthritis Staphylococcus aureus is the most common pathogen in all age groups and should be treated with antimicrobial regimens similar to those recommended for osteomyelitis, although generally a 2–3-week treatment regimen is sufficient. However, depending on the patient’s age, other pathogens may need consideration: • Among infants aged up to 3 months and some elderly patients, Enterobacteriaceae (e.g. Escherichia coli) and group B streptococci are common. • Infections with Haemophilus influenzae and Streptococcus pneu- moniae need to be considered in children aged from 3 months to 6 years. • Among sexually active young adults and teenagers, septic arthritis due to Neisseria gonorrhoeae is common.

57 WHO Model Prescribing Information — Drugs used in bacterial infections

Treatment Until the results of blood and synovial fluid culture are known, initial empirical therapy should be given.

Initial empirical therapy Adults. Cloxacillin 2g i.v. or i.m. every 6 hours plus ceftriaxone 1–2g i.v. or i.m. every 24 hours.

Children ≥ 2 months. Cloxacillin 25–50mg/kg (maximum 2g) i.v. or i.m. every 6 hours plus ceftriaxone 25–50mg/kg (maximum 2g) i.v. or i.m. every 24 hours.

Neonates. Cloxacillin 25–50mg/kg (maximum 2g) i.v. or i.m. every 6 hours plus cefotaxime 50–75mg/kg (maximum 2g) i.v. every 8 hours.

Once the pathogen has been identified, treatment should be adjusted appropriately.

Septic arthritis due to Staphylococcus aureus Adults. Cloxacillin 2g i.v. or i.m. every 6 hours for 2–3 weeks (if the duration of parenteral therapy is less than 2–3 weeks, the treatment course should be completed with cloxacillin 1g orally every 6 hours) or cefazolin 1–2g i.v. or i.m. every 8 hours for 2–3 weeks (if the duration of parenteral therapy is less than 2–3 weeks, the treat- ment course should be completed with cefalexin 1–2g orally every 6 hours) or clindamycin 600mg i.v. every 8 hours for 2–3 weeks (if the duration of parenteral therapy is less than 2–3 weeks, the treatment course should be completed with clindamycin 300– 450mg orally every 6 hours).

58 Bone and joint infections

Children > 5 years. Cloxacillin 25–50mg/kg (maximum 2g) i.v. or i.m. every 4–6 hours for 4–6 days (or until clinical improve- ment occurs), followed by cloxacillin 25mg/kg (maximum 500mg) orally every 6 hours to complete the treatment course of 2–3 weeks or ceftriaxone 50–75mg/kg (maximum 1g) i.v. or i.m. every 24 hours for 4–6 days (or until clinical improvement occurs), fol- lowed by cloxacillin 25mg/kg (maximum 500mg) or cefalexin 25mg/kg (maximum 500mg) orally every 6 hours to complete the treatment course of 2–3 weeks or cefazolin 15mg/kg (maximum 1g) i.v. or i.m. every 8 hours for 4–6 days (or until clinical improvement occurs), followed by cefalexin 25mg/kg (maximum 500mg) orally every 6 hours to complete the treatment course of 2–3 weeks or clindamycin 10mg/kg (maximum 450mg) i.v. every 6 hours for 4–6 days (or until clinical improvement occurs), followed by clindamycin 10mg/kg (maximum 450mg) orally every 6 hours to complete the treatment course of 2–3 weeks.

Children aged from 2 months to 5 years. Cloxacillin 25–50mg/kg (maximum 2g) i.v. or i.m. every 4–6 hours for 4–6 days (or until clinical improvement occurs) plus ceftriaxone 50–75mg/kg (maximum 1g) i.v. or i.m. every 24 hours for 4–6 days (or until clinical improvement occurs) followed by cloxacillin 12.5mg/kg (maximum 500mg) orally every 6 hours to complete the treatment course of 2–3 weeks.

Neonates. Cloxacillin 25–50mg/kg (maximum 2g) i.v. or i.m. every 4–6 hours for 4–6 days (or until clinical improvement occurs) plus

59 WHO Model Prescribing Information — Drugs used in bacterial infections

cefotaxime 50–75mg/kg (maximum 2g) i.v. every 8 hours for 4–6 days (or until clinical improvement occurs) followed by cloxacillin 12.5mg/kg (maximum 500mg) orally every 6 hours to complete the treatment course of 2–3 weeks.

Comments In some cases, especially in adults with infection due to Staphy- lococcus aureus, repeated aspiration or surgical washout of the joint may be necessary in addition to appropriate antimicrobial therapy.

60 Sexually transmitted diseases

Gonorrhoea Gonorrhoea results from infection with the Gram-negative coccus Neisseria gonorrhoeae. Gonococcal and chlamydial infec- tions often coexist. In women, gonorrhoea causes cervicitis. Examination of cervical smears is not reliable and cultures should be prepared whenever possible. In men, gonorrhoea is confirmed by demonstrating Gram-negative intracellular diplococci in urethral smears. Ideally, blood samples should be taken for serological tests to exclude concurrent infection with syphilis.

Treatment All patients with gonorrhoea should be treated concurrently for chlamydial infection unless microbiological facilities exist to exclude the latter diagnosis. Sexual partners should be treated simultaneously.

Gonococcal conjunctivitis threatens sight and progresses rapidly. Since it is highly contagious, every effort should be made to prevent transmission of infection. Antimicrobial therapy should be started immediately and the eyes should be irrigated frequently with saline solution.

Uncomplicated anogenital gonococcal infections in adults Ceftriaxone 250mg i.m. in a single dose or spectinomycin 2g i.m. in a single dose or ciprofloxacin 500mg orally in a single dose (contraindicated during pregnancy).

Disseminated gonococcal infections in adults Ceftriaxone 1g i.m. every 24 hours for 7 days or spectinomycin 2g i.m. every 12 hours for 7 days.

61 WHO Model Prescribing Information — Drugs used in bacterial infections

If there is evidence of meningeal or endocardial involvement, treatment should be extended to 2 weeks and 4 weeks, respectively.

Gonococcal conjunctivitis Adults. Ceftriaxone 250mg i.m. in a single dose or spectinomycin 2g i.m. in a single dose or ciprofloxacin 500mg orally in a single dose (contraindicated during pregnancy).

Neonates. Ceftriaxone 50mg/kg (maximum 125mg) i.m. in a single dose or cefotaxime 50mg/kg (maximum 2g) i.v. in a single dose or spectinomycin 25mg/kg (maximum 75mg) i.m. in a single dose.

If systemic treatment is not available and infection is con- firmed, tetracycline, 1% ointment, should be instilled into each eye every hour, pending referral of the infant for parenteral therapy.

All infants should receive topical antigonococcal therapy immediately after birth. Tetracycline, 1% ointment, should be applied after gently cleansing the eyelids. Erythromycin, 1% ointment, is as effective, but more expensive. Some authorities recommend that therapy should continue for 7 days.

Comments Neonates who fail to respond to treatment should be treated for chlamydial ophthalmia (see page 63).

Lymphogranuloma venereum Lymphogranuloma venereum is caused by Chlamydia

trachomatis serotypes L1, L2 and L3. The primary genital lesion,

62 Sexually transmitted diseases

which is rarely demonstrable in women, usually occurs in men as a purulent ulcer on the penis that heals within a few days. After a latent period of days or months, an acute fluctuant inguinal lymphadenopathy develops. In the late stages of the disease, chronic lymphatic obstruction may result in lymph- oedema (elephantiasis) of the external genitalia.

Treatment Doxycycline 100mg (children >8 years: 2mg/kg; maximum 100mg) orally every 12 hours for 14 days (contraindicated during pregnancy) or erythromycin 500mg (children: 12.5mg/kg; maximum 500mg) orally every 6 hours for 14 days. Other chlamydial infections Chlamydia trachomatis (serotypes D–K) causes non-gonococcal urethritis in men. It may also cause epididymitis and chronic prostatitis. In women, infection is associated with cervicitis, salpingitis and endometritis. Infants born to mothers with cer- vical infection may develop purulent conjunctivitis (chlamydial ophthalmia) or pneumonia.

All patients with chlamydial infections should be treated con- currently for gonorrhoea, unless microbiological facilities exist to exclude the latter diagnosis. In every instance, sexual part- ners should be treated simultaneously.

Treatment Doxycycline 100mg (children >8 years: 2mg/kg; maximum 100mg) orally every 12 hours for 7 days (contraindicated during pregnancy) or erythromycin 500mg (children: 10–15mg/kg; maximum 500mg) orally every 6 hours for 7 days.

Comments Infants with chlamydial ophthalmia should be treated with erythromycin syrup, 12.5mg/kg (maximum 500mg) orally every 6 hours for 14 days.

63 WHO Model Prescribing Information — Drugs used in bacterial infections

Vaginitis Vaginal discharge may be caused by candidiasis (due to Candida albicans), trichomoniasis (due to Trichomonas vaginalis) or bacterial vaginosis (due to Gardnerella vaginalis and vaginal anaerobes).

Treatment Candidiasis Nystatin pessaries 200000IU inserted high into the vagina nightly for 2 weeks (in some geographical areas, nightly doses as high as 1 million IU may be required).

Administration should be continued for 48 hours after clinical cure. Higher doses and a longer period of treatment may be required in immunocompromised patients.

Trichomoniasis Metronidazole 2g orally in a single dose (sexual partners should be treated simultaneously; contraindicated during preg- nancy).

Bacterial vaginosis Metronidazole 400–500mg orally every 12 hours for 7 days (contraindicated during pregnancy). Pelvic inflammatory disease Acute pelvic inflammatory disease is often a consequence of sexually transmitted disease. The pathogens most commonly involved are Neisseria gonorrhoeae and Chlamydia trachomatis. However, bacteria present in the normal vaginal flora, includ- ing streptococci, Escherichia coli, Haemophilus influenzae and anaerobes such as Bacteroides, Peptostreptococcus and Peptococcus spp. also often contribute. Trauma to the endocervical canal from an intrauterine device (IUD) may facilitate the ascent of these organisms into the endometrial cavity.

Treatment If an intrauterine device is in place, it should be removed.

Ambulatory patients Ceftriaxone 250mg i.m. in a single dose

64 Sexually transmitted diseases followed by doxycycline 100mg orally every 12 hours for 10 days (con- traindicated during pregnancy) plus metronidazole 400–500mg orally every 8 hours for 10 days (contraindicated during pregnancy).

Hospitalized patients with very severe disease Gentamicin 5–7mg/kg i.v. or i.m. every 24 hours or 1.5– 2.0mg/kg i.v. or i.m. every 8 hours for at least 4 days (or for 48 hours after clinical improvement occurs; contraindicated during pregnancy) plus clindamycin 900mg i.v. every 8 hours for at least 4 days (or for 48 hours after clinical improvement occurs) followed by doxycycline 100mg orally every 12 hours for 10–14 days (con- traindicated during pregnancy).

Hospitalized patients with moderate or severe disease Ceftriaxone 250mg i.m. every 12 hours for at least 4 days (or for 48 hours after clinical improvement occurs) followed by doxycycline 100mg orally every 12 hours for 10–14 days (con- traindicated during pregnancy).

Alternative regimen. Ciprofloxacin 500mg orally every 12 hours for at least 4 days (or for 48 hours after clinical improvement occurs; contraindicated during pregnancy) plus metronidazole 400–500mg orally every 8 hours for at least 4 days (or for 48 hours after clinical improvement occurs; con- traindicated during pregnancy) followed by doxycycline 100mg orally every 12 hours for 10–14 days (con- traindicated during pregnancy).

65 WHO Model Prescribing Information — Drugs used in bacterial infections

Syphilis Syphilis is caused by the spirochaete Treponema pallidum. Transmission results almost exclusively from sexual contact with infected persons, but infection can also be transmitted from mother to fetus during pregnancy and through blood transfusion.

Where facilities and resources are available, all patients and their contacts should be concurrently tested and treated, as appropriate, for chlamydial infection, gonorrhoea and HIV infection according to national policy. Patients with a history of primary or secondary syphilis should be tested for the presence of specific antitreponemal antibodies, which indicate latent syphilis.

Doses are for adults, except where otherwise specified.

Treatment Early syphilis (< 2 years’ duration) Benzathine benzylpenicillin 2.4 million IU i.m. in a single dose or procaine benzylpenicillin 1 million IU i.m. every 24 hours for 10 days.

Late syphilis (other than neurosyphilis) Benzathine benzylpenicillin 2.4 million IU i.m. weekly for 3 weeks or procaine benzylpenicillin 1 million IU i.m. every 24 hours for 3 weeks.

Neurosyphilis Benzylpenicillin 4 million IU i.v. every 4 hours for 2 weeks.

Alternative regimen. Procaine benzylpenicillin 1 million IU i.m. every 24 hours for 2 weeks plus probenecid 500mg orally every 6 hours for 2 weeks.

66 Sexually transmitted diseases

Congenital syphilis Children > 2 years. Benzylpenicillin 200000–300000IU/kg (maximum 2.4 million IU) i.v. or i.m. weekly in divided doses for 2 weeks.

Children £ 2 years. Benzylpenicillin 25000IU/kg (maximum 1.5 million IU) i.v. or i.m. every 12 hours for 10 days or procaine benzylpenicillin 50000IU/kg (maximum 1.5 million IU) i.m. every 24 hours for 10 days.

Patients allergic to penicillins Doxycycline 100mg (children >8 years: 2mg/kg; maximum 100mg) orally every 12 hours for 30 days (contraindicated during pregnancy) or erythromycin 500mg (children: 7.5–12.5mg/kg; maximum 250mg) orally every 6 hours for 15 days. Chancroid Chancroid, which results from infection with Haemophilus ducreyi, is the most common cause of genital ulceration in developing countries and its incidence has been rising with increasing rates of HIV infection. Clinically, the disease is readily confused with syphilis. When facilities for dark-field microscopy and serological diagnosis of syphilis are not avail- able, benzathine benzylpenicillin should always be adminis- tered at the same time.

Doses are for adults.

Treatment Erythromycin 500mg orally every 6 hours for 7 days or ciprofloxacin 500mg orally in a single dose (contraindicated during pregnancy) or ceftriaxone 250mg i.m. in a single dose

67 WHO Model Prescribing Information — Drugs used in bacterial infections

or spectinomycin 2g i.m. in a single dose.

Longer treatment courses may be necessary in immunocom- promised patients. Granuloma inguinale Granuloma inguinale (donovanosis) is a chronic granuloma- tous infection caused by the Gram-negative encapsulated bac- terium Calymmatobacterium granulomatis.

Doses are for adults.

Treatment Sulfamethoxazole 800mg + trimethoprim 160mg orally every 12 hours for 14 days (or until the lesion has completely healed) or doxycycline 100mg orally every 12 hours for 14 days (or until the lesion has completely healed; contraindicated during pregnancy) or chloramphenicol 500mg orally every 6 hours for 3 weeks (or until the lesion has completely healed).

68 Cardiovascular infections

Infective endocarditis Infective endocarditis is a difficult disease to diagnose and treat. It is most commonly caused by a-haemolytic (“viridans”) streptococci, enterococci and Staphylococcus aureus. a-Haemolytic streptococci and enterococci usually affect pre- viously damaged valves, whereas S. aureus can affect normal valves. Most cases of fulminant endocarditis are caused by S. aureus.

Blood cultures are usually positive and all efforts should be made to identify the responsible pathogen and to obtain antimicrobial susceptibility data before commencing treatment. All three pathogens may be resistant to common antimicro- bials: a-haemolytic streptococci to penicillins; enterococci to penicillins, gentamicin (high-level resistance) and occasionally vancomycin; and S. aureus to penicillins. It is therefore essen- tial to obtain blood cultures (preferably three sets, each from a separate venepuncture) before starting antimicrobial treatment.

When gentamicin is used in combination with a b-lactam antimicrobial in the treatment of endocarditis it should be administered every 8 hours. Basal plasma levels of gentamicin should not exceed 1mg/l. If vancomycin is used, peak plasma levels of 30–40mg/l and basal plasma levels of 5–15mg/l are recommended. These levels are specific for the management of endocarditis and do not apply to other circumstances. Initial empirical therapy Treatment Benzylpenicillin 3 million IU (children: 50000IU/kg; maximum 3 million IU) i.v. every 4 hours plus cloxacillin 2g (children: 50mg/kg; maximum 2g) i.v. every 4 hours plus

69 WHO Model Prescribing Information — Drugs used in bacterial infections

gentamicin 2mg/kg (children: 2.5mg/kg; maximum 80mg) i.v. every 8 hours (contraindicated during pregnancy).

Patients allergic to penicillins or with nosocomial infections Vancomycin 1g (children: 20mg/kg; maximum 1g) i.v. every 12 hours plus gentamicin 2mg/kg (children: 2.5mg/kg; maximum 80mg) i.v. every 8 hours (contraindicated during pregnancy).

Comments The maximum period of gentamicin therapy without monitor- ing plasma levels should be 72 hours. There are currently no data available regarding once-daily gentamicin administration for the treatment of endocarditis. Accordingly the drug should be administered in 2–4 divided doses daily to maintain con- stant plasma levels. Once a pathogen has been identified, treat- ment should be amended as necessary. Endocarditis due to a-haemolytic streptococci a-Haemolytic streptococci are usually highly susceptible to benzylpenicillin. The minimum inhibitory concentration (MIC) of benzylpenicillin for the infecting strain should be deter- mined, as this influences the need for and duration of con- comitant gentamicin therapy. Most strains of a-haemolytic streptococci have both MIC and minimum bactericidal con- centrations (MBC) of <0.2mg/l, but a few demonstrate anti- microbial resistance (i.e. have an MBC/MIC ratio ≥32). For infections involving a resistant strain, or where the MIC is unknown, treatment should be as for strains resistant to benzylpenicillin (MIC = 0.25–1.0mg/l).

Treatment Uncomplicated endocarditis Benzylpenicillin 3 million IU (children: 100000IU/kg; maxi- mum 3 million IU) i.v. every 4 hours for 2 weeks plus gentamicin 1mg/kg (adults and children) i.v. every 8 hours for 2 weeks (contraindicated during pregnancy).

70 Cardiovascular infections

Alternative regimen. Benzylpenicillin 3 million IU (children: 100000IU/kg; maximum 3 million IU) i.v. every 4 hours for 4 weeks.

Strains highly susceptible to benzylpenicillin (MIC £ 0.12 mg/l) Benzylpenicillin 3 million IU (children: 100000IU/kg; maxi- mum 3 million IU) i.v. every 4 hours for 4 weeks plus gentamicin 1mg/kg (adults and children) i.v. every 8 hours for 2 weeks (contraindicated during pregnancy).

Strains resistant to benzylpenicillin (MIC = 0.25–1.0 mg/l) Gentamicin 1mg/kg (adults and children) i.v. every 8 hours for 4–6 weeks (contraindicated during pregnancy) plus either benzylpenicillin 3–4 million IU (children: 100000IU/kg; 4 million IU) i.v. every 4 hours for 6 weeks or ampicillin 2g (children: 50mg/kg; maximum 2g) i.v. every 4 hours for 6 weeks.

Comments a-Haemolytic streptococci with high-level resistance to peni- cillins are encountered in the USA, but are less common else- where. Treatment of such strains is usually with intravenous vancomycin plus gentamicin, as for prosthetic valve endo- carditis (see page 73). Endocarditis due to enterococci The causative organisms of enterococcal endocarditis, such as Enterococcus faecalis, usually have reduced susceptibility to penicillins (MIC = 0.5–2.0mg/l) and always require the con- comitant use of gentamicin for optimal bactericidal activity.

Treatment Gentamicin 1mg/kg (adults and children) i.v. every 8 hours for 4–6 weeks (contraindicated during pregnancy) plus either benzylpenicillin 3–4 million IU (children: 100000IU/kg; maxi- mum 4 million IU) i.v. every 4 hours for 6 weeks

71 WHO Model Prescribing Information — Drugs used in bacterial infections

or ampicillin 2g (children: 50mg/kg; maximum 2g) i.v. every 4 hours for 6 weeks.

Comments Enterococci with high-level resistance to penicillins are encoun- tered in the USA, but are less common elsewhere. Treatment of such strains is usually with intravenous vancomycin plus gen- tamicin, as for prosthetic valve endocarditis (see page 73). Enterococci should be tested for high-level resistance to amino- glycosides; if this is present, combination therapy with gen- tamicin will not be effective. Treatment of such strains is difficult and consultation with a specialist is recommended. Endocarditis due to Staphylococcus aureus Because of the frequency with which valvular destruction may rapidly progress and require surgical intervention, patients with endocarditis due to Staphylococcus aureus should be referred for early consultation with a cardiac surgeon.

Treatment Strains susceptible to meticillin Cloxacillin 2g (children: 50mg/kg; maximum 2g) i.v. every 4 hours for 6 weeks plus gentamicin 1mg/kg (adults and children) i.v. every 8 hours for 7 days (contraindicated during pregnancy).

Strains resistant to meticillin Vancomycin 1g i.v. every 12 hours (children: 40mg/kg (maximum 1g) i.v. in 2–4 divided doses daily) for 6 weeks. Culture-negative endocarditis Culture-negative endocarditis may be due to previous treat- ment with antimicrobials or to unusual microorganisms, such as fastidious streptococci, Legionella spp., Bartonella spp., Cox- iella burnetii (the cause of Q fever) or fungi, including Candida albicans. Unless Q fever or fungal infection is strongly sus- pected, patients with culture-negative endocarditis should be treated with benzylpenicillin plus gentamicin, as for endo-

72 Cardiovascular infections

carditis due to enterococci (see page 71), followed by monitor- ing and adjustment of therapy as indicated. Prosthetic valve endocarditis Prosthetic valve endocarditis may be caused by staphylococci (particularly coagulase-negative staphylococci), Corynebac- terium spp., Streptococcus spp., enteric Gram-negative rods, Pseudomonas aeruginosa and fungi, including Candida albicans. Because of increasing resistance of coagulase-negative staphy- lococci to cloxacillin, initial empirical therapy should include vancomycin plus gentamicin. Early consultation with a cardiac surgeon is imperative.

Treatment Vancomycin 1g i.v. every 12 hours (children: 40mg/kg (maximum 1g) i.v. in 2–4 divided doses daily) for 6 weeks plus gentamicin 1mg/kg (adults and children) i.v. every 8 hours for 6 weeks (contraindicated during pregnancy).

Comments If infection due to a Gram-negative bacterial pathogen is sus- pected, the dose of gentamicin should be increased to 2mg/kg i.v. every 8 hours. Monitoring of gentamicin and vancomycin levels is important (see page 69). Pericarditis and myocarditis Pericarditis and myocarditis are not common and may be due to non-infectious causes such as rheumatic fever, collagen dis- eases, uraemia and myocardial infarction. Infectious causes include viruses (e.g. coxsackie viruses A and B), bacteria (e.g. Staphylococcus aureus and Mycobacterium tuberculosis), fungi and parasites (e.g. Toxoplasma gondii). Bacterial pathogens are treated according to their known or suspected antimicrobial susceptibility. Rheumatic fever Rheumatic fever is relatively rare in developed countries, but remains a common problem in developing countries. It occurs as a delayed sequela of infection with Streptococcus pyogenes.

73 WHO Model Prescribing Information — Drugs used in bacterial infections

Pharyngeal infection with S. pyogenes may be mild or subclini- cal. The mainstay of treatment for symptomatic acute disease is salicylates or corticosteroids (in severe cases), but a 10-day course of oral phenoxymethylpenicillin should also be given to eradicate the organism from the pharynx. For details of chemo- prophylaxis in patients with a history of rheumatic fever, see pages 89–91.

74 Central nervous system infections

Meningitis Bacterial meningitis is most often caused by Haemophilus influenzae serotype b, Neisseria meningitidis and Streptococcus pneumoniae. Childhood vaccination against H. influenzae serotype b is strongly encouraged to prevent meningitis.

Bacterial meningitis is an acute disease characterized by rapid onset of fever, severe headache and stiffness of the neck, fol- lowed by confusion and ultimately coma. In meningitis due to N. meningitidis a haemorrhagic rash may also be present. Meningitis due to H. influenzae mainly affects young children, but meningitis due to N. meningitidis and S. pneumoniae may affect any age group. A lumbar puncture should be performed, white cells counted and their type determined (granulocytes, lymphocytes) and a cerebrospinal fluid sample sent for culture and susceptibility testing of bacterial isolates. In areas endemic for the disease where the organism is not known, therapy should encompass all three possible pathogens. Because of the potential severity of this disease, treatment should be started promptly and not delayed for the results of lumbar puncture. Initial empirical therapy Treatment Ceftriaxone 2g (children: 50–100mg/kg; maximum 2g) i.v. or i.m. daily in one or two divided doses for up to 14 days.

Alternative regimen Benzylpenicillin 3–4 million IU (children: 100000IU/kg; maxi- mum 4 million IU) i.v. or i.m. every 4 hours for up to 14 days plus chloramphenicol 1g (children: 25mg/kg; maximum 1g) i.v. every 6 hours for up to 14 days (once clinical improvement occurs, chloramphenicol 500–750mg (children: 25mg/kg; maximum 750mg) orally every 6 hours may be substituted).

75 WHO Model Prescribing Information — Drugs used in bacterial infections

Comments In areas where 10% or more of cases of invasive meningitis due to S. pneumoniae are caused by strains with intermediate resistance to benzylpenicillin, initial empirical therapy should be with ceftriaxone or cefotaxime (for neonates; see page 79). Meningitis due to Neisseria meningitidis Treatment Benzylpenicillin 3–4 million IU (children: 100000IU/kg; maxi- mum 4 million IU) i.v. or i.m. every 4 hours for up to 14 days plus chloramphenicol oily suspension 100mg/kg (maximum 3g) (children: 25mg/kg; maximum 500mg) i.m. every 24 hours for up to 14 days (once clinical improvement occurs, chloram- phenicol 500–750mg (children: 25mg/kg; maximum 750mg) orally every 6 hours may be substituted).

Prophylaxis Rifampicin 600mg (neonates <1 month: 5mg/kg (maximum 300mg); children ≥1 month: 10mg/kg (maximum 600mg)) orally every 12 hours for 2 days or ciprofloxacin 500mg (adults and children) orally in a single dose (contraindicated during pregnancy).

Comments Prophylaxis should be considered for patients and their close contacts, especially children. Meningitis due to Streptococcus pneumoniae Treatment Strains susceptible to benzylpenicillin (MIC £ 0.06 mg/l) Benzylpenicillin 3–4 million IU (children: 100000IU/kg; maxi- mum 4 million IU) i.v. or i.m. every 4 hours for 10–14 days or ceftriaxone 2g (children: 50–100mg/kg; maximum 2g) i.v. or i.m. daily in one or two divided doses for 10–14 days.

Patients who are very ill may require treatment for up to 3 weeks.

76 Central nervous system infections

Strains showing intermediate resistance to benzylpenicillin (MIC = 0.125–1.0 mg/l) Ceftriaxone 2g (children: 50–100mg/kg; maximum 2g) i.v. or i.m. daily in one or two divided doses for 10–14 days.

Strains resistant to benzylpenicillin (MIC >1.0 mg/l) or ceftriaxone/ cefotaxime (MIC ≥1.0 mg/l) Vancomycin 1g i.v. every 12 hours (children: 20mg/kg (maximum 1g) i.v. every 6 hours) for at least 14 days plus ceftriaxone 2g (children: 50–100mg/kg; maximum 2g) i.v. or i.m. every 12 hours for at least 14 days plus rifampicin 600mg (children: 20mg/kg; maximum 600mg) orally every 24 hours for at least 14 days.

Comments Several strains have been described that are resistant to cefo- taxime or ceftriaxone (MIC ≥1.0mg/l). Susceptibility tests should therefore be conducted before starting treatment to check whether the isolate is susceptible to cefotaxime or cef- triaxone. If the patient fails to respond to cefotaxime or cef- triaxone and continues to have a positive cerebrospinal fluid culture, the addition of vancomycin should be consid- ered. If resistance to cefotaxime or ceftriaxone is commonly encountered, empirical therapy should be as for strains resistant to benzylpenicillin (MIC >1.0mg/l) or ceftriaxone/ cefotaxime (see above).

Patients with benzylpenicillin-resistant or ceftriaxone/ cefotaxime-resistant S. pneumoniae should be referred to a specialist. Meningitis due to Haemophilus influenzae Treatment Ceftriaxone 2g (children: 50mg/kg; maximum 2g) i.v. or i.m. every 12 hours for 7–10 days or ampicillin 2–3g (children: 50mg/kg; maximum 3g) i.v. every 4–6 hours for 7–10 days

77 WHO Model Prescribing Information — Drugs used in bacterial infections

or chloramphenicol 1g (children: 25mg/kg; maximum 1g) i.v. every 6 hours for 7–10 days.

Prophylaxis Rifampicin 600mg (neonates <1 month: 5mg/kg (maximum 300mg); children ≥1 month: 20mg/kg (maximum 600mg)) orally every 24 hours for 4 days.

Comments Ampicillin and chloramphenicol should only be used if the isolate is known to be susceptible.

Prophylaxis should be considered for patients and their close contacts, especially children under 5 years. Ceftriaxone clears carriage, thus patients treated with this drug will generally not require prophylaxis with rifampicin. Meningitis due to Listeria monocytogenes Listeria monocytogenes is a common cause of meningitis and/or septicaemia in newborn babies and immunosuppressed adults.

Treatment Adults Benzylpenicillin 3 million IU i.v. or i.m. every 4 hours for at least 3 weeks or ampicillin 3g i.v. every 6 hours for at least 3 weeks or sulfamethoxazole 800mg + trimethoprim 160mg i.v. every 6 hours for at least 3 weeks.

Neonates Ampicillin 50mg/kg (maximum 2g) i.v. every 8 hours (neonates < 7 days: 50mg/kg (maximum 2g) i.v. every 12 hours) for a total of 3 weeks plus gentamicin 2.5mg/kg i.v. every 12 hours for 3 weeks.

78 Central nervous system infections

Comments Benzylpenicillin and ampicillin appear to be equally effective. Therapy often needs to be prolonged; some patients may require treatment for up to 6 weeks.

Although gentamicin is recommended for this indication in neonates, it does not appear to be of value in adults. Neonatal meningitis The organisms that cause neonatal meningitis are similar to those that cause neonatal septicaemia and pneumonia — namely Streptococcus pneumoniae, group A and group B strep- tococci and Escherichia coli. In some regions Listeria monocyto- genes or Enterococcus faecalis may also be responsible. Treatment options are similar to those recommended for neonatal pneu- monia (see pages 25–26).

Treatment (where the pathogen is unknown) Ampicillin 50mg/kg (maximum 2g) i.v. every 8 hours (neo- nates <7 days: 50mg/kg (maximum 2g) i.v. every 12 hours) for a total of 7–10 days plus either gentamicin 2.5mg/kg i.v. every 12 hours for 7–10 days or cefotaxime 50mg/kg (maximum 2g) i.v. every 12 hours for 7–10 days.

Comments Meningitis due to Listeria monocytogenes is especially common in the first week of life — thus ampicillin should be included in the regimen.

Meningitis due to group B streptococci Group B streptococci often colonize the vagina and rectum of pregnant women. These organisms can be transmitted to newborn babies during labour and cause infection. Meningitis and septicaemia occurring during the first week after birth may be particularly severe.

79 WHO Model Prescribing Information — Drugs used in bacterial infections

Treatment Benzylpenicillin 50000–75000IU/kg (maximum 2 million IU) i.v. every 4–6 hours (neonates <7 days: benzylpenicillin 50000IU/kg (maximum 2 million IU) i.v. every 8 hours) for a total of 3 weeks plus gentamicin 2.5mg/kg i.v. every 12 hours for 3 weeks.

Comments Chemoprophylaxis against vaginal or rectal infections with group B streptococci during pregnancy remains controversial. Some clinicians recommend administration of a single dose of benzylpenicillin during labour to women who have risk factors for perinatal transmission of infection, such as premature rupture of membranes or prolonged labour. Brain abscess Most brain abscesses are polymicrobial, the most common pathogens being Streptococcus anginosus (milleri) and anaerobic bacteria. Other pathogens, such as Nocardia spp. and Toxoplasma gondii (especially in HIV-infected patients), may also be respon- sible. Aspiration or surgical drainage should be considered to guide antimicrobial therapy and to reduce the volume of the abscess. The duration of treatment depends on the clinical response and radiological evidence of resolution of the abscess.

Treatment Benzylpenicillin 3–4 million IU (children: 100000IU/kg; maxi- mum 3 million IU) i.v. or i.m. every 4–6 hours plus either metronidazole 500mg (children: 12.5mg/kg; maximum 500mg) i.v. every 8–12 hours (contraindicated during pregnancy) or chloramphenicol 1g (children: 25mg/kg; maximum 750mg) i.v. every 6 hours.

80 Miscellaneous infections

Lyme disease Lyme disease is caused by the spirochaete Borrelia burgdorferi, which is transmitted by a number of tick species, including Ixodes dammini. The disease presents as skin lesions (erythema chronicum migrans), headache, fever, malaise and fatigue. Some patients develop recurrent arthritis and occasionally neurological and cardiac complications. Early disease Treatment Doxycycline 100mg (children >8 years: 2mg/kg; maximum 100mg) orally every 12 hours for 10–21 days (contraindicated during pregnancy) or amoxicillin 500mg (children: 15mg/kg; maximum 500mg) orally every 8 hours for 10–21 days. Late disease (chronic arthritis, cardiac and neurological manifestations) Doses refer to adults, as this condition is not found in children.

Treatment Benzylpenicillin 4 million IU i.v. every 4–6 hours for 14–21 days or ceftriaxone 2g i.v. or i.m. every 24 hours for 14–21 days. Patients with neurological involvement usually require treat- ment for 21 days. Relapsing fever Relapsing fever is a louse-borne disease caused by the spirochaete Borrelia recurrentis, which occurs mainly in tropical countries.

Treatment Doxycycline 100mg (children >8 years: 2mg/kg; maximum 100 mg) orally in a single dose (contraindicated during pregnancy)

81 WHO Model Prescribing Information — Drugs used in bacterial infections

or erythromycin 500mg (children: 12.5mg/kg; maximum 500mg) orally in a single dose or chloramphenicol 500mg (children: 25mg/kg; maximum 750mg) orally in a single dose. Leptospirosis Leptospirosis is caused by spirochaetes of the Leptospira genus. The severity of the disease ranges from subclinical infection to serious haemorrhagic conditions with high mortality.

Treatment Benzylpenicillin 2 million IU (children: 50000IU/kg; maximum 2 million IU) i.v. every 6 hours for 5–7 days or doxycycline 100mg (children >8 years: 2mg/kg; maximum 100mg) orally every 12 hours for 5–7 days (contraindicated during pregnancy). Brucellosis Brucellosis is acquired from livestock, and is an occupational disease of butchers, farmers and abattoir workers. Most cases are caused by two related bacteria, Brucella abortus and B. melitensis; infection by the latter species is more severe. The disease is characterized by a fluctuating fever (“undulant fever”), aches and pains, and occasionally arthritis or osteomyelitis.

Treatment Adults and children > 8 years Doxycycline 100mg (children >8 years: 2mg/kg; maximum 100mg) orally every 12 hours for 6 weeks (contraindicated during pregnancy) plus either streptomycin 1g (children: 15mg/kg; maximum 1g) i.m. every 24 hours for 2 weeks (contraindicated during pregnancy) or gentamicin 5–7mg/kg i.v. every 24 hours (children: 7.5mg/kg i.v. in 1–3 divided doses daily) for 2 weeks (contraindicated during pregnancy)

82 Miscellaneous infections

or rifampicin 600mg (children: 15mg/kg; maximum 600mg) orally every 24 hours for 6 weeks.

Children £ 8 years Sulfamethoxazole 20mg/kg + trimethoprim 4mg/kg (maxi- mum 800mg + 160mg) orally every 12 hours for 6 weeks plus either rifampicin 15mg/kg ( maximum 600mg) orally every 24 hours for 6 weeks or gentamicin 7.5mg/kg i.v. in 1–3 divided doses daily for 2 weeks. Tularaemia Tularaemia is caused by Francisella tularensis and transmitted to humans from rodents through the bite of the deer fly, Chrysops discalis, and other insects. It has a number of febrile clinical pre- sentations, including ulceroglandular, glandular, oculoglan- dular, oropharyngeal, typhoidal or pulmonary (tularaemic pneumonia). Treatment Streptomycin 15mg/kg (adults and children; maximum 1g) i.m. every 24 hours for 7–14 days (contraindicated during pregnancy) or gentamicin 1.5mg/kg (adults and children) i.v. or i.m. every 8 hours for 7 days (contraindicated during pregnancy). Comments Ciprofloxacin 500mg (children: 15mg/kg; maximum 500mg) orally every 12 hours for 10–14 days (contraindicated during pregnancy) and chloramphenicol 1g (children: 25mg/kg; maximum 1g) i.v. every 6 hours for 7 days are also used for this indication. Anthrax Anthrax is primarily a septicaemic infection of livestock caused by Bacillus anthracis. Human infection mainly results from cutaneous inoculation of organisms from infected animals,

83 WHO Model Prescribing Information — Drugs used in bacterial infections

with the development of a cutaneous lesion. In addition to anti- microbials, anti-anthrax serum may be used, although its ef- ficacy is controversial.

Treatment Benzylpenicillin 4 million IU (children: 100000IU/kg; maxi- mum 4 million IU) i.v. or i.m. every 4–6 hours for 7–10 days or doxycycline 100mg (children >8 years: 2mg/kg; maximum 100mg) orally every 12 hours for 7–10 days (contraindicated during pregnancy) or ciprofloxacin 750mg (children: 10–15mg/kg; maximum 750mg) orally every 12 hours for 7–10 days (contraindicated during pregnancy). Plague Plague is an acute infectious disease with a high fatality rate, caused by the bacterium Yersinia pestis. It is primarily a disease of ground rodents in Africa, the Americas and central and south-east Asia and is transmitted to humans from infected rodents by fleas. It may occur in epidemics. Cutaneous infec- tion from the flea bites causes acute suppurative lymphadeni- tis (bubonic plague) with high fever, septicaemia and sometimes haemorrhage. Pneumonic plague, which is caused by the inhalation of airborne bacilli, may be rapidly fatal.

Treatment Doxycycline 100mg (children >8 years: 2mg/kg; maximum 100mg) orally every 12 hours for 7 days (contraindicated during pregnancy) or chloramphenicol 500mg (children: 25mg/kg; maximum 750mg) orally or i.v. every 6 hours for 7–10 days or gentamicin 1.7mg/kg (adults and children) i.v. or i.m. every 8 hours for 7 days (contraindicated during pregnancy)

84 Miscellaneous infections

or streptomycin 1g (children: 15mg/kg; maximum 1g) i.m. every 12 hours for 7–10 days (contraindicated during pregnancy). Rickettsial infections These infections include typhus fever due to Rickettsia prowazekii (epidemic typhus or louse-borne typhus), typhus fever due to R. typhii (murine typhus fever), typhus fever due to R. tsut- sugamashi (scrub typhus), rickettsialpox due to R. akari and spotted fever due to R. rickettsii (Rocky Mountain spotted fever).

Treatment Doxycycline 100mg (children >8 years: 2mg/kg; maximum 100mg) orally every 12 hours for 7–10 days (or for 48 hours after resolution of fever; contraindicated during pregnancy) or chloramphenicol 500mg (children: 15mg/kg; maximum 500mg) orally or i.v. every 6 hours for 7–10 days (or for 48 hours after resolution of fever). Q fever Q fever is a febrile infectious disease, usually acute, caused by Coxiella burnetti. On rare occasions infection may become latent and reappear as chronic Q fever, usually complicated by chronic hepatitis, thrombocytopenia and endocarditis. If left untreated, chronic Q fever with endocarditis is invariably fatal.

Treatment Adults and children > 8 years Doxycycline 100mg (children >8 years: 2mg/kg; maximum 100mg) orally every 12 hours for 7–10 days (contraindicated during pregnancy).

Children ≤ 8 years Erythromycin 10–15mg/kg (maximum 500mg) orally every 6 hours for 7–10 days.

85 Septicaemia

Septicaemia is invasion of the bloodstream by bacteria, giving rise to fever and hypotension. It may be associated with infection in specific sites (e.g. the lungs, urinary tract, gastrointestinal tract) or there may be no clear originating focus. Septicaemia occurs more commonly in patients who are immunosuppressed, including those with HIV infection and diabetes. In previously healthy persons, Staphylococcus aureus, Streptococcus pneumoniae and Escherichia coli are the most fre- quent causes, while in immunosuppressed patients, Gram- negative bacteria, including Pseudomonas aeruginosa, may also be responsible. Other febrile illnesses such as typhoid fever and malaria may be difficult to differentiate clinically from infections caused by these pathogens. Initial empirical therapy Initial empirical therapy should be directed against the most likely pathogens and subsequently amended when the respon- sible pathogen is identified and its susceptibility to antimicro- bials tested. Since the treatment options depend on the most likely infective source, clinicians should consult the most appropriate section in these guidelines (e.g. urinary tract infec- tions) for specific recommendations. If a good clinical response is observed but bacterial isolates appear to be resistant in vitro, the possibility that the isolate is a contaminant should be con- sidered unless it is isolated repeatedly. A change of therapy may not be mandatory if the clinical response is adequate.

The pathogens responsible for hospital-acquired (nosocomial) septicaemia depend on the type of patient, the underlying disease and recent medical and surgical treatment. The micro- bial flora of hospitals vary greatly in type and susceptibility. The choice of initial therapy therefore depends on factors such as the characteristics of the patient and the likely source of sepsis.

86 Septicaemia

Treatment Adults and children > 5 years Gentamicin 5–7mg/kg i.v. every 24 hours or 1.5mg/kg i.v. or i.m. every 8 hours (contraindicated during pregnancy) plus either cloxacillin 2g i.v. every 4–6 hours or cefazolin 1–2g i.v. every 8 hours or clindamycin 600mg i.v. every 8 hours or chloramphenicol 750mg i.v. every 6 hours.

Children aged from 2 months to 5 years Cloxacillin 50mg/kg (maximum 2g) i.v. every 4–6 hours plus ceftriaxone 50mg/kg (maximum 2g) i.v. or i.m. every 24 hours.

Neonates Ampicillin 50mg/kg (maximum 2g) i.v. every 8 hours (neonates <7 days: 50mg/kg (maximum 2g) i.v. every 12 hours) plus gentamicin 2.5mg/kg i.v. every 12 hours.

Alternative regimen. Cloxacillin 50mg/kg (maximum 2g) i.v. every 4–6 hours plus cefotaxime 50–75mg/kg (maximum 2g) i.v. every 8 hours.

87 Prophylaxis

Surgical prophylaxis The most essential factors influencing surgical infections are asepsis and good surgical techniques. Preoperative chemo- prophylaxis for certain surgical procedures is widely practised and can reduce the incidence of postoperative wound infec- tions. It is necessary to select antimicrobials for this purpose which are directed against the organisms likely to be encoun- tered during the specified procedure. The sources of organisms which may cause infection are mainly endogenous from the patient’s own normal microbial flora at the site of the operation (e.g. skin, mouth, gastrointestinal tract, vagina or urinary tract). The timing of the antimicrobial administration should ensure that adequate tissue levels of drug are present for the entire duration of the operation (from incision until final closure of the wound) and that the duration of administration is as short as possible, while being compatible with clinical efficacy.

Staphylococcus aureus and coagulase-negative staphylococci may cause infection in both clean and clean–contaminated surgery. Cefazolin has been used extensively to prevent such infections in circumstances where they may have serious con- sequences. Antimicrobial therapy is needed for the gastroin- testinal tract and possibly for other colonized sites to prevent infection with anaerobes and enterobacteria. Metronidazole, gentamicin, amoxicillin and amoxicillin + clavulanic acid have been used for this purpose. Clean surgery (e.g. prosthetic implants, vascular surgery) Prophylaxis Cefazolin 1g (adults and children) i.v. at induction of anaes- thesia (if the operation is prolonged beyond 3–4 hours a further 1-g dose should be administered).

88 Prophylaxis

Contaminated surgery Prophylaxis Regimen 1 Cefazolin 1g (adults and children) i.v. at induction of anaes- thesia (if the operation is prolonged beyond 3–4 hours a further 1-g dose should be administered) plus metronidazole 500mg (adults and children) i.v. at induction of anaesthesia (contraindicated during pregnancy).

Regimen 2 Clindamycin 600mg (adults and children) i.v. at induction of anaesthesia plus gentamicin 5mg/kg (adults and children) i.v. at induction of anaesthesia (contraindicated during pregnancy).

Regimen 3 Amoxicillin 500mg + clavulanic acid (children: 125mg) i.v. at induction of anaesthesia. Non-surgical prophylaxis Prevention of recurrence of rheumatic fever (secondary prophylaxis) For individuals who have had an initial attack of rheumatic fever, whether or not they have rheumatic heart disease, con- tinuous administration of an antimicrobial (secondary prophy- laxis) is strongly advised to prevent infection of the upper respiratory tract by group A b-haemolytic streptococci and therefore to reduce the risk of recurrent attacks.

Various regimens have been suggested, although regular i.m. injections of benzathine benzylpenicillin are most effective. Although usually given every 4 weeks, recent data suggest that administration every 3 weeks is more effective in preventing recurrences of rheumatic fever, especially in high-risk patients. Among patients for whom regular injections of benzathine benzylpenicillin are not a treatment option, an alternative (but less effective option) is daily oral phenoxymethylpenicillin;

89 WHO Model Prescribing Information — Drugs used in bacterial infections

however, it may be difficult to maintain adherence. Alternative agents for patients who are allergic to penicillins include either oral sulfonamides (although they are not effective for treat- ing established infections with group A streptococci) or erythromycin.

There are several variables that affect the likelihood of recur- rences of rheumatic fever, including the time since the most recent attack, the age of the patient and the risk posed by the environment. The duration of secondary prophylaxis should be adapted to the individual patient but some general principles can be stated: • Patients without carditis in a previous attack should have prophylaxis for a minimum of 5 years after the last attack, and at least until 18 years of age (often longer if substantial risk factors are present). • Patients with documented cardiac involvement in the initial attack should continue prophylaxis at least until 25 years of age (longer if environmental conditions or other factors pose a substantial risk). • Patients with chronic valvular rheumatic heart disease should have prophylaxis for prolonged periods — lifelong in some cases. • Prophylaxis should be continued during pregnancy. However, sulfonamides should be avoided, as they present a risk to the fetus.

Prophylaxis Adults and children > 30 kg Benzathine benzylpenicillin 1.2 millionIU i.m. every 3–4 weeks or phenoxymethylpenicillin 250mg (children >2 years: 125mg) orally every 12 hours.

Children £ 30 kg Benzathine benzylpenicillin 600000IU i.m. every 3–4 weeks or phenoxymethylpenicillin 125mg (children >2 years) orally every 12 hours.

90 Prophylaxis

Patients allergic to penicillins Erythromycin 250mg (adults and children) orally every 12 hours or sulfadiazine 1g (children: 500mg) orally or i.v. every 24 hours. Postsplenectomy prophylaxis The main method of protection following splenectomy is by vaccination against Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis. Even in patients vaccinated appropriately, the risk of overwhelming bacterial sepsis is life- long. The risk is greatest in young children in the first 2 years following splenectomy, but is also high in the under-fives (especially those with sickle-cell anaemia) and patients with severe immunosuppression. Antimicrobial therapy should therefore be assessed on an individual basis, particularly in these groups.

Prophylaxis Amoxicillin 250mg (children >2 years: 20mg/kg; maximum 250mg) orally every 24 hours or phenoxymethylpenicillin 250mg (children >2 years: 125mg) orally every 12 hours or erythromycin 250mg (children: 7.5mg/kg; maximum 250mg) orally every 24 hours.

91 Drugs (for details of contraindications, etc., see individual drug entries) Amoxicillin Capsule or tablet, 250mg, 500mg (anhydrous) Powder for oral suspension, 125mg (anhydrous)/5 ml

• osteomyelitis due to b-haemolytic General information streptococci in adults, together with Amoxicillin is an aminopenicillin which benzylpenicillin is active against many strains of Entero- • osteomyelitis due to Salmonella spp. £ bacteriaceae. It is better absorbed from in children 5 years, together with the gastrointestinal tract than ampicillin. cloxacillin and either ceftriaxone or Thus, amoxicillin is used whenever oral cefotaxime administration is appropriate and ampi- • Lyme disease (early stage). cillin is used parenterally. Peak plasma Postsplenectomy prophylaxis. concentrations are reached after 1–2 hours. It is largely excreted in the Dosage and administration urine both as unchanged drug and as Acute pharyngitis and acute cervical metabolites. adenitis Adults: 500mg orally every 8 hours for Clinical information 10 days. Children: 15mg/kg (maximum 500mg) Uses orally every 8 hours for 10 days. Treatment of: • acute pharyngitis, acute cervical Acute otitis media and acute adenitis, acute otitis media, acute bronchitis sinusitis and acute bronchitis Adults: 500mg orally every 8 hours for • pneumonia in adults and children > 5 5 days. years Children: 15mg/kg (maximum 500mg) • mild pneumonia in children aged orally every 8 hours for 5 days. from 2 months to 5 years • neonatal pneumonia, together with Acute sinusitis gentamicin Adults: 500mg orally every 8 hours for • acute exacerbations of chronic bron- 7–10 days. chitis in adults Children: 15mg/kg (maximum 500mg) • chronic suppurative lung disease in orally every 8 hours for 7–10 days. children • tooth abscesses and suppurative Acute exacerbations of chronic odontogenic infections bronchitis in adults • cellulitis and erysipelas, together with 500mg orally every 8 hours for 5 days. benzylpenicillin • acute gastritis and peptic ulcer disease Chronic suppurative lung disease in in adults, together with metronida- children zole and either bismuth salicylate or 30mg/kg (maximum 1 g) orally every 8 omeprazole hours for 5 days.

92 Drugs

Pneumonia in adults and children Acute gastritis and peptic ulcer > 5 years disease in adults Ambulatory patients 500mg orally every 6 hours for 2 weeks, Adults: 500mg orally every 8 hours for supplemented by bismuth salicylate 5 days. 107.7mg (1 tablet) orally every 6 hours plus metronidazole 200mg orally every Children > 5 years: 15 mg/kg (maximum 8 hours and 400mg orally at night or 500 mg) orally every 8 hours for 5 days. 500mg orally every 8 hours for 2 weeks, Mild pneumonia in children aged supplemented by metronidazole 400mg from 2 months to 5 years orally every 8 hours and omeprazole 15–25 mg/kg (maximum 500 mg) orally 40mg orally every 24 hours. every 8 hours for 5 days or 15–25 mg/kg Osteomyelitis due to b-haemolytic (maximum 500 mg) orally every 8 hours streptococci in adults to complete the treatment course of at 1g orally every 6–8 hours to complete least 5 days, following initial treatment the treatment course of 2–4 weeks, fol- with procaine benzylpenicillin 50 000 lowing initial therapy with benzylpeni- IU/kg (maximum 900 000 IU) i.m. every cillin 2 million IU i.v. or i.m. every 4–6 24 hours for at least 3 days. hours. Neonatal pneumonia Osteomyelitis due to Salmonella 30 mg/kg i.v. every 12 hours, together spp. in children £ 5 years with gentamicin 2.5 mg/kg i.v. every 8 Children aged from 2 months to 5 years: hours (neonates < 7 days: gentamicin 7.5–15mg/kg (maximum 1g) orally 2.5 mg/kg i.v. every 12 hours) for a total every 8 hours to complete the treatment of at least 5 days. course of 6 weeks, following initial Tooth abscesses and suppurative therapy with cloxacillin 25–50mg/kg odontogenic infections (maximum 2g) i.v. or i.m. every 4–6 Adults: 250mg orally every 8 hours for 3 hours and ceftriaxone 50–75mg/kg days. (maximum 1g) i.v. or i.m. every 24 hours for 4–6 days (or until clinical improve- Children: 25mg/kg (maximum 250mg) ment occurs). orally every 8 hours for 3 days. Neonates: 7.5–15mg/kg (maximum 1g) Cellulitis and erysipelas orally every 8 hours to complete the Adults: 500mg orally every 8 hours to treatment course of 6 weeks, following complete the treatment course of 7–10 initial therapy with cloxacillin 25–50 days, following initial treatment with mg/kg (maximum 2g) i.v. or i.m. every benzylpenicillin 1–2 million IU i.v. or i.m. 4–6 hours and cefotaxime 50–75mg/kg every 6 hours. (maximum 2 g) i.v. every 8 hours for 4– 6 days (or until clinical improvement Children: 7.5–15mg/kg (maximum occurs). 500mg) orally every 8 hours to complete the treatment course of 7–10 days, Lyme disease (early stage) following initial treatment with benzyl- Adults: 500mg orally every 8 hours for penicillin 50000–100000IU/kg (maxi- 10–21 days. mum 2 million IU) i.v. or i.m. every 6 hours. Children: 15mg/kg (maximum 500mg) orally every 8 hours for 10–21 days. Postsplenectomy prophylaxis Adults: 250mg orally every 24 hours.

93 WHO Model Prescribing Information — Drugs used in bacterial infections

Amoxicillin (continued) Adverse effects Hypersensitivity reactions range in Children > 2 years: 20mg/kg (maximum severity from skin rashes to immediate 250mg) orally every 24 hours. anaphylaxis. Erythematous maculo- papular rashes are common and usually Contraindications occur within 3–14 days after the start of Known hypersensitivity to penicillins. treatment, initially appearing on the trunk and thereafter spreading peripher- Precautions ally to involve most of the body. In most Facilities should be available for treating instances the rash is mild and subsides anaphylaxis whenever penicillins are after 6–14 days despite continuation of used. Patients should be questioned therapy. carefully about previous allergic reac- Diarrhoea can occur. Interstitial nephri- tions before the first dose is adminis- tis, neutropenia and thrombocytopenia tered. If a skin rash develops during have been reported. treatment or no improvement occurs within 2 days, the patient should be transferred to a different class of Overdosage antimicrobial. Overdosage can cause convulsions, paralysis and even death. Use in pregnancy Excessive blood concentrations can be There is no evidence that amoxicillin lowered by haemodialysis. is teratogenic. It may be used during pregnancy. Storage Preparations should be stored in tightly closed containers, protected from light.

Amoxicillin + clavulanic acid Tablet, 500mg of amoxicillin + 125mg of clavulanic acid

General information Clinical information The two components of this combination Uses product operate synergistically because Treatment of: clavulanic acid binds to b-lactamases • infections caused by susceptible b- and thereby competitively protects lactamase-producing strains of Esche- the amoxicillin against resistant richia coli, Haemophilus influenzae, Kleb- b-lactamase-producing strains. Both siella spp. and Staphylococcus aureus components are well absorbed after oral (where amoxicillin alone is not appro- administration and are distributed into priate) the lungs, pleural fluid and peritoneal • acute otitis media and acute sinusitis fluid. They are largely excreted • acute exacerbations of chronic bron- unchanged in the urine. chitis in adults

94 Drugs

• aspiration pneumonia and lung lowing initial therapy with procaine abscesses benzylpenicillin 1.5 million IU i.m. every • human and animal bites and 24 hours for 5 days. clenched-fist injuries, together with + procaine benzylpenicillin Children: amoxicillin 15mg/kg clavu- • urinary tract infections in children lanic acid (maximum 500mg) orally • osteomyelitis due to Haemophilus every 8 hours for 5 days, following initial influenzae or unknown pathogen in therapy with procaine benzylpenicillin children £ 5 years, together with 50000IU/kg (maximum 1.5 million IU) cloxacillin and either ceftriaxone or i.m. every 24 hours for 5 days. cefotaxime. Urinary tract infections in children Prophylaxis in contaminated surgery. Amoxicillin 7.5mg/kg + clavulanic acid (maximum 250mg) orally every 8 hours Dosage and administration for 5–10 days. + The dosage for amoxicillin clavulanic Osteomyelitis due to Haemophilus acid is expressed in terms of the amoxi- influenzae or unknown pathogen in cillin component. children £ 5 years Acute otitis media Children aged from 2 months to 5 years: Adults: amoxicillin 500mg + clavulanic amoxicillin 15mg/kg + clavulanic acid acid orally every 8 hours for 5 days. (maximum 500mg) orally every 8 hours to complete the treatment course of 3–4 Children: amoxicillin 7.5–15mg/kg + weeks, following initial therapy with clavulanic acid (maximum 500mg) cloxacillin 25–50mg/kg (maximum 2g) orally every 8 hours for 5 days. i.v. or i.m. every 4–6 hours and ceftriax- Acute sinusitis one 50–75mg/kg (maximum 1g) i.v. or i.m. every 24 hours for 4–6 days (or until Adults: amoxicillin 500mg + clavulanic clinical improvement occurs). acid orally every 8 hours for 7–10 days. Neonates: amoxicillin 15mg/kg + Children: amoxicillin 7.5–15mg/kg + clavulanic acid (maximum 500mg) clavulanic acid (maximum 500mg) orally every 8 hours to complete the orally every 8 hours for 7–10 days. treatment course of 3–4 weeks, following Acute exacerbations of chronic initial therapy with cloxacillin 25– bronchitis in adults 50mg/kg (maximum 2g) i.v. or i.m. Amoxicillin 500mg + clavulanic acid every 4–6 hours and cefotaxime 50– orally every 8 hours for 5 days. 75mg/kg (maximum 2 g) i.v. every 8 hours for 4–6 days (or until clinical Aspiration pneumonia and lung improvement occurs). abscesses Adults: amoxicillin 500mg + clavulanic Prophylaxis in contaminated acid orally every 8 hours for 14 days. surgery Adults: amoxicillin 500mg + clavulanic Children: amoxicillin 15mg/kg + clavu- acid i.v. at induction of anaesthesia. lanic acid (maximum 500mg) orally every 8 hours for 14 days. Children: amoxicillin 125mg + clavu- lanic acid i.v. at induction of anaesthesia. Human and animal bites and clenched-fist injuries Adults: amoxicillin 500mg + clavulanic acid orally every 8 hours for 5 days, fol-

95 WHO Model Prescribing Information — Drugs used in bacterial infections

Amoxicillin + clavulanic acid anaphylaxis. Erythematous maculo- (continued) papular rashes are common and usually occur within 3–14 days after the start of Contraindications treatment, initially appearing on the Known hypersensitivity to penicillins. trunk and thereafter spreading peripher- ally to involve most of the body. In most Precautions instances the rash is mild and subsides Facilities should be available for treating after 6–14 days despite continuation of anaphylaxis whenever penicillins are therapy. used. Patients should be questioned Hepatotoxicity is more frequent than carefully about previous allergic reac- with amoxicillin. tions before the first dose is adminis- tered. If a skin rash develops during Diarrhoea can occur. Interstitial nephri- treatment or no improvement occurs tis, neutropenia and thrombocytopenia within 2 days, the patient should have been reported. be transferred to a different class of antimicrobial. Overdosage Overdosage can cause convulsions, Use in pregnancy paralysis and even death. + There is no evidence that amoxicillin Excessive blood concentrations can be clavulanic acid is teratogenic. It may be lowered by haemodialysis. used during pregnancy. Storage Adverse effects Preparations should be stored in tightly Hypersensitivity reactions range in closed containers, protected from light. severity from skin rashes to immediate

Ampicillin Tablet, 250mg (as sodium salt) Powder for injection, 500mg (as sodium salt) in vial

General information Clinical information Ampicillin is a semisynthetic penicillin Uses which is active against many strains of Treatment of: Enterobacteriaceae, including shigellae. • acute mastoiditis It is moderately absorbed from the gas- • typhoid and paratyphoid fever in chil- trointestinal tract. Peak plasma levels are dren who are chronic carriers attained after approximately 2 hours. • acute cholecystitis, endocarditis due The drug is concentrated in the bile, to a-haemolytic streptococci resistant undergoes enterohepatic circulation and to benzylpenicillin and endocarditis is excreted in appreciable amounts in the due to enterococci, together with faeces. gentamicin

96 Drugs

• acute peritonitis, together with gen- gentamicin 7.5mg/kg i.v. in 1–3 divided tamicin and metronidazole doses daily and metronidazole • acute pyelonephritis, together with 12.5mg/kg (maximum 500mg) i.v. every gentamicin or ceftriaxone 8–12 hours for at least 7 days. • meningitis due to Haemophilus influen- zae Acute pyelonephritis • meningitis due to Listeria monocyto- Adults: 1–2g i.v. or i.m. every 6 hours for genes in adults up to 14 days, supplemented for the first • neonatal meningitis due to Listeria 7 days by gentamicin 5–7mg/kg orally monocytogenes and neonatal septi- daily in divided doses or for 14 days caemia (initial empirical therapy), by ceftriaxone 1g i.v. or i.m. every together with gentamicin. 24 hours. • neonatal meningitis due to unknown Children: 50mg/kg (maximum 2g) i.v. pathogen, together with gentamicin or or i.m. every 6 hours for up to 14 days, cefotaxime. supplemented for the first 7 days by gen- tamicin 7.5mg/kg orally in 1–3 divided Dosage and administration doses daily or for 14 days by ceftriaxone Intravenous formulations of ampicillin 50mg/kg (maximum 1g) i.v. or i.m. should be administered over 2 minutes. every 24 hours. Acute mastoiditis Endocarditis due to a-haemolytic Adults: 2g i.v. every 6 hours for 10–14 streptococci resistant to benzyl- days. penicillin (MIC = 0.25–1.0mg/l) and Children: 25–50mg/kg (maximum 2g) endocarditis due to enterococci i.v. every 6 hours for 10–14 days. Adults: 2g i.v. every 4 hours for 6 weeks, supplemented for 4–6 weeks Typhoid and paratyphoid fever in by gentamicin 1mg/kg i.v. every children who are chronic carriers 8 hours. 250mg i.m. every 6 hours for 4–6 weeks. Children: 50mg/kg (maximum 2g) i.v. Acute cholecystitis every 4 hours for 6 weeks, supplemented Adults: 1–2g i.v. or i.m. every 6 hours, for 4–6 weeks by gentamicin 1mg/kg i.v. together with gentamicin 5–7mg/kg every 8 hours. i.v. daily in divided doses for up to 7 Meningitis due to Haemophilus days. influenzae Children: 25–50mg/kg (maximum 2g) Adults: 2–3g i.v. every 4–6 hours for 7–10 i.v. or i.m. every 6 hours, together with days. gentamicin 7.5mg/kg i.v. in 1–3 divided Children: 50mg/kg (maximum 3g) i.v. doses daily for up to 7 days. every 4–6 hours for 7–10 days. Acute peritonitis Ampicillin should only be used if the Adults: 2g i.v. or i.m. every 6 hours, isolate is known to be susceptible. together with gentamicin 5–7mg/kg i.v. daily in divided doses and metronid- Prophylaxis with rifampicin 600 mg azole 500mg i.v. every 8–12 hours for at (neonates < 1 month: 5 mg/kg (maximum least 7 days. 300 mg); children ≥ 1 month: 20 mg/kg (maximum 600 mg)) orally every 24 Children: 50mg/kg (maximum 2g) i.v. hours for 4 days should be considered or i.m. every 6 hours, together with

97 WHO Model Prescribing Information — Drugs used in bacterial infections

Ampicillin (continued) used. Patients should be questioned carefully about previous allergic reac- for patients and their close contacts, tions before the first dose is adminis- especially children under 5 years. tered. If a skin rash develops during treatment or no improvement occurs Meningitis due to Listeria within 2 days, the patient should monocytogenes be transferred to a different class of Adults: 3g i.v. every 6 hours for at least antimicrobial. 3 weeks. Neonates: 50mg/kg i.v. every 8 hours Use in pregnancy (neonates < 7 days: 50mg/kg i.v. every There is no evidence that ampicillin 12 hours) for a total of 3 weeks, supple- is teratogenic. It may be used during mented by gentamicin 2.5mg/kg i.v. pregnancy. every 12 hours. Adverse effects Treatment must be continued for at least Hypersensitivity reactions range in 48–72 hours after the patient becomes severity from skin rashes to immediate asymptomatic. anaphylaxis. Erythematous maculo- Therapy often needs to be prolonged in papular rashes are common and usually adults; some patients may require treat- occur within 3–14 days after the start of ment for up to 6 weeks. treatment, initially appearing on the trunk and thereafter spreading peripher- Neonatal meningitis due to unknown ally to involve most of the body. In most pathogen instances the rash is mild and subsides 50 mg/kg (maximum 2 g) i.v. every 8 after 6–14 days despite continuation of hours (neonates < 7 days: 50 mg/kg therapy. (maximum 2 g) i.v. every 12 hours) for a total of 7–10 days, supplemented by Diarrhoea is more frequent than with either gentamicin 2.5 mg/kg i.v. every 12 amoxicillin. hours or cefotaxime 50 mg/kg (maxi- Interstitial nephritis, neutropenia and mum 2 g) i.v. every 12 hours. thrombocytopenia have been reported. Initial empirical therapy for neonatal septicaemia Overdosage 50 mg/kg (maximum 2 g) i.v. every 8 Overdosage from large intravenous hours (neonates < 7 days: 50 mg/kg doses can cause convulsions, paralysis (maximum 2 g) i.v. every 12 hours), sup- and even death. plemented by gentamicin 2.5 mg/kg i.v. Excessive blood concentrations can be every 12 hours. lowered by haemodialysis.

Contraindications Storage Known hypersensitivity to penicillins. Preparations should be stored in tightly closed containers, protected from light. Precautions Facilities should be available for treating anaphylaxis whenever penicillins are

98 Drugs

Benzylpenicillin Powder for injection, 600mg (= 1 million IU), 3g (= 5 million IU) (sodium or potassium salt) in vial

• neurosyphilis in adults and congenital General information syphilis Benzylpenicillin is a b-lactam antibiotic • infective endocarditis (initial empiri- produced by Penicillium notatum. It cal therapy), together with cloxacillin is bactericidal against streptococci, and gentamicin a Haemophilus spp., neisseriae, many • endocarditis due to -haemolytic anaerobes and spirochaetes. streptococci, endocarditis due to ente- rococci and culture-negative endo- After intramuscular injection, peak carditis, together with gentamicin plasma concentrations are reached • meningitis (initial empirical therapy) within 15–30 minutes. It is widely dis- and meningitis due to Neisseria menin- tributed throughout the body. It does not gitidis, together with chloramphenicol readily enter the cerebrospinal fluid, • meningitis due to Listeria monocy- except when the meninges are inflamed. togenes in adults and meningitis due It has a plasma half-life of 30–45 minutes to benzylpenicillin-susceptible Strep- and is excreted mainly in the urine. tococcus pneumoniae • neonatal meningitis due to group B streptococci, together with gentamicin Clinical information • brain abscess, together with metroni- Uses dazole or chloramphenicol • Lyme disease (late stage) in adults, Benzylpenicillin is used when high leptospirosis and anthrax. concentrations of a narrow-spectrum penicillin are required. Dosage and administration Treatment of: Benzylpenicillin is destroyed by gastric acid and must be administered parenter- • pneumonia in adults and children > 5 ally. The powder for injection should years, together with gentamicin be diluted in “water for injection” in • atypical pneumonia in adults and accordance with the manufacturer’s children > 5 years, together with gen- instructions. tamicin and erythromycin • very severe and severe pneumonia in Pneumonia in adults and children children aged from 2 months to 5 > 5 years years Hospitalized patients • aspiration pneumonia and lung ab- Adults: 2 million IU i.v. or i.m. every scesses, together with metronidazole 4–6 hours for 5 days or 2 million IU i.v. or • cellulitis and erysipelas and osteomye- i.m. every 4–6 hours, together with gen- litis due to b-haemolytic streptococci tamicin 5–7mg/kg i.v. daily in divided in adults, together with amoxicillin doses for 7 days. • streptococcal necrotizing fasciitis, together with clindamycin Children >5 years: 50000–100000IU/kg • gangrene, together with gentamicin (maximum 2 million IU) i.v. or i.m. every and metronidazole 4–6 hours for 5 days or 50000–100000 IU/kg (maximum 2 million IU) i.v. or

99 WHO Model Prescribing Information — Drugs used in bacterial infections

Benzylpenicillin (continued) mg/kg (maximum 500mg) orally every 8 hours may be substituted). i.m. every 4–6 hours, together with gen- tamicin 7.5mg/kg i.v. in 1–3 divided Streptococcal necrotizing fasciitis doses daily for 7 days. Adults: 4 million IU i.v. or i.m. every 4 hours, together with clindamycin 600mg Patients with atypical pneumonia i.v. every 8 hours for at least 7 days. should also receive erythromycin 1g (children: 10mg/kg; maximum 1g) i.v. Children: 100000IU/kg (maximum 4 every 6 hours for 14 days. million IU) i.v. or i.m. every 4 hours, together with clindamycin 10mg/kg Benzylpenicillin may be used alone (maximum 450mg) i.v. every 6 hours when Streptococcus pneumoniae is the sus- for at least 7 days. pected pathogen. Gangrene Very severe and severe pneumonia Adults: 4 million IU i.v. or i.m. every 4 in children aged from 2 months to 5 hours for at least 7 days, together with years gentamicin 5–7mg/kg i.v. or i.m. daily in 50000–100000IU/kg (maximum 2 million divided doses and metronidazole 500mg IU) i.v. or i.m. every 4–6 hours for at least i.v. every 8 hours (once clinical im- 5 days. provement occurs, rectal formulations of metronidazole may be substituted). Aspiration pneumonia and lung abscesses Children: 100000IU/kg (maximum 4 Adults: 1–2 million IU i.v. or i.m. every million IU) i.v. or i.m. every 4 hours for 4–6 hours for 10–14 days, together with at least 7 days, together with gentamicin metronidazole 500mg i.v. every 8–12 7.5mg/kg i.v. or i.m. in 1–3 divided doses hours (once clinical improvement daily and metronidazole 12.5 mg/kg occurs, metronidazole 400mg orally (maximum 500mg) i.v. every 8 hours every 12 hours may be substituted). (once clinical improvement occurs, rectal formulations of metronidazole may be Children: 50000–100000IU/kg (maxi- substituted). mum 2 million IU) i.v. or i.m. every 4–6 hours for 10–14 days, together with Osteomyelitis due to b-haemolytic metronidazole 12.5mg/kg (maximum streptococci in adults 500mg) i.v. every 8–12 hours (once clini- 2 million IU i.v. or i.m. every 4–6 hours cal improvement occurs, metronidazole for 2–4 weeks (if the duration of par- 10mg/kg (maximum 400mg) orally enteral therapy is less than 2–4 weeks, every 12 hours may be substituted). the treatment course should be com- pleted with amoxicillin 1g orally every Cellulitis and erysipelas 6–8 hours). Adults: 1–2 million IU i.v. or i.m. every 6 hours for 7–10 days (once clinical im- Neurosyphilis in adults provement occurs, amoxicillin 500mg 4 million IU (2.4g) i.v. every 4 hours for orally every 8 hours may be substituted). 2 weeks. Children: 50000–100000IU/kg (maxi- Congenital syphilis mum 2 million IU) i.v. or i.m. every 6 Children > 2 years: 200000–300000IU/kg hours for 7–10 days (once clinical im- (maximum 2.4 million IU) i.v. or i.m. in provement occurs, amoxicillin 7.5–15 divided doses weekly for 2 weeks.

100 Drugs

Children £ 2 years: 25000IU/kg (maxi- Children: 100000IU/kg (maximum 4 mum 1.5 million IU) i.v. or i.m. every 12 million IU) i.v. every 4 hours for 6 weeks, hours for 10 days. supplemented for 4–6 weeks by genta- micin 1mg/kg i.v. every 8 hours. Initial empirical therapy for infective endocarditis Endocarditis due to enterococci and Adults: 3 million IU i.v. every 4 hours, culture-negative endocarditis together with cloxacillin 2g i.v. every 4 Adults: 3–4 million IU i.v. every 4 hours hours and gentamicin 2mg/kg i.v. every for 6 weeks, supplemented for 4–6 weeks 8 hours. by gentamicin 1mg/kg i.v. every 8 hours. Children: 50000IU/kg (maximum 3 million IU) i.v. every 4 hours, together Children: 100000IU/kg (maximum 4 with cloxacillin 50mg/kg (maximum million IU) i.v. every 4 hours for 6 weeks, 2g) i.v. every 4 hours and gentamicin supplemented for 4–6 weeks by genta- 2.5mg/kg (maximum 80mg) i.v. every micin 1mg/kg i.v. every 8 hours. 8 hours. Initial empirical therapy for Endocarditis due to a-haemolytic meningitis streptococci Adults: 3–4 million IU i.v. or i.m. every 4 Uncomplicated endocarditis hours for up to 14 days, supplemented Adults: 3 million IU i.v. every 4 hours, by chloramphenicol 1g i.v. every 6 hours together with gentamicin 1 mg/kg i.v. (once clinical improvement occurs, every 8 hours for 2 weeks or 3 million IU chloramphenicol 500–750mg orally i.v. every 4 hours for 4 weeks. every 6 hours may be substituted). Children: 100 000 IU/kg (maximum 3 Children: 100000IU/kg (maximum 4 million IU) i.v. every 4 hours, together million IU) i.v. or i.m. every 4 hours for with gentamicin 1 mg/kg i.v. every 8 up to 14 days, supplemented by chlor- hours for 2 weeks or 100 000 IU/kg amphenicol 25mg/kg (maximum 1g) i.v. (maximum 3 million IU) i.v. every 4 every 6 hours (once clinical improve- hours for 4 weeks. ment occurs, chloramphenicol 25mg/kg (maximum 750mg) orally every 6 hours Strains highly susceptible to benzyl- may be substituted). penicillin (MIC £ 0.12mg/l) Adults: 3 million IU i.v. every 4 hours for Meningitis due to Neisseria 4 weeks, supplemented for the first 2 meningitidis weeks by gentamicin 1mg/kg i.v. every Adults: 3–4 million IU i.v. or i.m. every 4 8 hours. hours for up to 14 days, supplemented by chloramphenicol oily suspension Children: 100000IU/kg (maximum 3 100mg/kg (maximum 3g) i.m. every million IU) i.v. every 4 hours for 4 weeks, 24 hours (once clinical improvement supplemented for the first 2 weeks by occurs, chloramphenicol 500–750mg gentamicin 1mg/kg i.v. every 8 hours. orally every 6 hours may be substituted). Strains resistant to benzylpenicillin Children: 100000IU/kg (maximum 4 (MIC 0.25–1.0mg/l) = million IU) i.v. or i.m. every 4 hours for Adults: 3–4 million IU i.v. every 4 hours up to 14 days, supplemented by chlor- for 6 weeks, supplemented for 4–6 weeks amphenicol oily suspension 25mg/kg by gentamicin 1mg/kg i.v. every 8 (maximum 500mg) i.m. every 24 hours hours. (once clinical improvement occurs,

101 WHO Model Prescribing Information — Drugs used in bacterial infections

Benzylpenicillin (continued) Lyme disease (late stage) in adults 4 million IU i.v. every 4–6 hours for 14–21 chloramphenicol 25mg/kg (maximum days. 750mg) orally every 6 hours may be substituted). Patients with neurological involvement usually require treatment for 21 days. Meningitis due to Streptococcus pneumoniae (strains susceptible to Leptospirosis benzylpenicillin (MIC £ 0.06mg/l)) Adults: 2 million IU i.v. every 6 hours for Adults: 3–4 million IU i.v. or i.m. every 5–7 days. 4 hours for 10–14 days. Children: 50000IU/kg (maximum 2 Children: 100000IU/kg (maximum 4 million IU) i.v. every 6 hours for 5–7 million IU) i.v. or i.m. every 4 hours for days. 10–14 days. Anthrax Patients who are very ill may require Adults: 4 million IU i.v. or i.m. every 4–6 treatment for up to 3 weeks. hours for 7–10 days. Meningitis due to Listeria Children: 100000IU/kg (maximum 4 monocytogenes in adults million IU) i.v. or i.m. every 4–6 hours for 3 million IU i.v. or i.m. every 4 hours for 7–10 days. at least 3 weeks. Contraindications Therapy often needs to be prolonged in Known hypersensitivity to penicillins or adults; some patients may require treat- cefalosporins. ment for up to 6 weeks. Neonatal meningitis due to group B Precautions streptococci Facilities should be available for treating 50 000–75 000 IU/kg (maximum 2 million anaphylaxis whenever penicillins are IU) i.v. every 4–6 hours (neonates < 7 used. Patients should be questioned days: 50 000 IU/kg (maximum 2 million carefully about previous allergic reac- IU) i.v. every 8 hours) for a total of 3 tions before the first dose is adminis- weeks, supplemented by gentamicin tered. If a skin rash develops during 2.5 mg/kg i.v. every 12 hours. treatment, the patient should be transferred to a different class of Brain abscess antimicrobial. Adults: 3–4 million IU i.v. or i.m. every Rapid intravenous administration of 4–6 hours, together with either metroni- large doses of sodium benzylpenicillin dazole 500mg i.v. every 8–12 hours or may cause hyperkalaemia, dysrhyth- chloramphenicol 1g i.v. every 6 hours. mias and cardiac arrest, particularly in Children: 100000IU/kg (maximum 3 patients with impaired renal function. million IU) i.v. or i.m. every 4–6 hours, together with either metronidazole Use in pregnancy 12.5mg/kg (maximum 500mg) i.v. every There is no evidence that benzylpeni- 8–12 hours or chloramphenicol 25mg/kg cillin is teratogenic. It may be used (maximum 750mg) i.v. every 6 hours. during pregnancy. The duration of treatment depends on the clinical response and radiological evidence of resolution of the abscess.

102 Drugs

Adverse effects Interstitial nephritis has been reported. Hypersensitivity reactions are most Neutropenia and thrombocytopenia are common, ranging in severity from skin rare. rashes to immediate anaphylaxis. Overdosage Pain and sterile inflammation can occur Overdosage with large intravenous at the site of intramuscular injection; doses can cause convulsions, paralysis phlebitis or thrombophlebitis sometimes and even death. follows intravenous administration. Acci- dental injection into a peripheral nerve Excessive blood concentrations can be causes severe pain and dysfunction. lowered by haemodialysis.

Unduly high concentrations of ben- Storage zylpenicillin in the brain can result in Powder for injection should be stored in confusion, convulsions, coma and fatal vials at 2–8 °C. encephalopathy.

Benzathine benzylpenicillin Powder for injection, 1.44g of benzylpenicillin (= 2.4 million IU) in 5-ml vial

Dosage and administration General information Acute pharyngitis and acute cervical Benzathine benzylpenicillin is a reposi- adenitis tory preparation of benzylpenicillin Adults and children > 30kg: 1.2 million which is available for parenteral use. It is IU i.m. in a single dose. designed to provide a tissue depot from Children £ 30kg: 30000IU/kg (maxi- which the drug is slowly absorbed over mum 1.2 million IU) i.m. in a single dose. a period of 12 hours to several days. It takes 13–24 hours to reach its peak Diphtheria plasma concentration, which is main- Adults and children > 30kg: 1.2 million tained over a period of about 14 days. It IU i.m. in a single dose, following ini- is detectable in the urine for 3–4 weeks. tial therapy with diphtheria antitoxin 20000–100000IU i.v. or i.m. Clinical information Children £30kg: 30000IU/kg (maximum 600 000 IU) i.m. in a single dose, follow- Uses ing initial therapy with diphtheria anti- Treatment of: toxin 20000–100000IU i.v. or i.m. • acute pharyngitis, acute cervical Vaccination with diphtheria–pertussis– adenitis and diphtheria tetanus (DPT) should be offered during • early and late syphilis (other than convalescence. neurosyphilis) in adults. Prevention of recurrence of rheumatic Early syphilis in adults fever due to group A b-haemolytic 2.4 million IU i.m. in a single dose. streptococci.

103 WHO Model Prescribing Information — Drugs used in bacterial infections

Benzathine benzylpenicillin during treatment, the patient should (continued) be transferred to a different class of antimicrobial. Late syphilis (other than neuro- syphilis) in adults Use in pregnancy 2.4 million IU i.m. weekly for 3 weeks. There is no evidence that benzathine benzylpenicillin is teratogenic. It may be Prevention of recurrence of rheuma- used during pregnancy. tic fever due to group A b-haemolytic streptococci Adverse effects Adults and children > 30kg: 1.2 million IU i.m. every 3–4 weeks. Hypersensitivity reactions are most common, ranging in severity from skin Children £ 30kg: 600000IU i.m. every rashes to immediate anaphylaxis. 3–4 weeks. Pain and sterile inflammation can Contraindications occur at the site of intramuscular injection. Accidental injection into a Known hypersensitivity to penicillins or peripheral nerve causes severe pain and cefalosporins. dysfunction. Precautions Interstitial nephritis has been reported. Facilities should be available for treating anaphylaxis whenever penicillins are Neutropenia and thrombocytopenia are used. Patients should be questioned rare. carefully about previous allergic reactions before the first dose is Storage administered. If a skin rash develops Powder for injection should be stored in vials at 2–8 °C.

Procaine benzylpenicillin Powder for injection, 1g of benzylpenicillin (= 1 million IU), 3g of benzylpenicillin (= 3 million IU) in vial

General information Clinical information Procaine benzylpenicillin is a repository Uses preparation of benzylpenicillin which Treatment of: is available for parenteral use. It is • diphtheria designed to provide a tissue depot from • very severe pneumonia in children which the drug is slowly absorbed over aged from 2 months to 5 years a period of 12 hours to several days. It • mild pneumonia in children aged produces a peak plasma concentration from 2 months to 5 years, together within 1–3 hours and is excreted over a with amoxicillin period of several days.

104 Drugs

• gingival infections, periodontitis, Children: 50000IU/kg (maximum 1 tooth abscesses and suppurative million IU) i.m. every 24 hours for 5 odontogenic infections days. • severe acute cervical adenitis in chil- dren < 5 years Tooth abscesses and suppurative • cellulitis and erysipelas odontogenic infections • human and animal bites and Adults: 1 million IU i.m. every 24 hours clenched-fist injuries, together with for 3 days. amoxicillin + clavulanic acid Children: 50000IU/kg (maximum 1 • early and late syphilis in adults, million IU) i.m. every 24 hours for 3 and congenital syphilis in children £ 2 days. years • neurosyphilis in adults, together with Severe acute cervical adenitis in probenecid. children < 5 years 50 000 IU/kg (maximum 1 million IU) Dosage and administration i.m. every 24 hours for at least 10 days. Diphtheria Cellulitis and erysipelas Adults: 1.2 million IU i.m. every 24 hours for 7 days, following initial therapy with Adults: 1.5 million IU i.m. every 24 hours diphtheria antitoxin 20000–100000IU i.v. for 7–10 days. or i.m. Children: 50000IU/kg (maximum 1.5 Children: 50000IU/kg (maximum 1.2 million IU) i.m. every 24 hours for 7–10 million IU) i.m. every 24 hours for 7 days. days, following initial therapy with Human and animal bites and diphtheria antitoxin 20000–100000IU i.v. clenched-fist injuries or i.m. Adults: 1.5 million IU i.m. every 24 hours Vaccination with diphtheria–pertussis– for 5 days, followed by amoxicillin 500 tetanus (DPT) should be offered during mg + clavulanic acid orally every 8 hours convalescence. for 5 days. Very severe pneumonia in children Children: 50000IU/kg (maximum 1.5 aged from 2 months to 5 years million IU) i.m. every 24 hours for 5 50000IU/kg (maximum 900000IU) i.m. days, followed by amoxicillin 15mg/kg + every 24 hours for at least 5 days. clavulanic acid (maximum 500mg) orally every 8 hours for 5 days. Mild pneumonia in children aged from 2 months to 5 years Early syphilis in adults 50000IU/kg (maximum 900000IU) i.m. 1 million IU i.m. every 24 hours for 10 every 24 hours for at least 3 days (once days. clinical improvement occurs, amoxicillin Late syphilis (other than neuro- 15–25mg/kg (maximum 500mg) orally syphilis) in adults every 8 hours may be used to complete 1 million IU i.m. every 24 hours for 3 the treatment course of at least 5 days). weeks. Gingival infections and periodontitis Neurosyphilis in adults Adults: 1 million IU i.m. every 24 hours 1 million IU i.m. every 24 hours, together for 5 days. with probenecid 500mg orally every 6 hours for 2 weeks.

105 WHO Model Prescribing Information — Drugs used in bacterial infections

Procaine benzylpenicillin Use in pregnancy (continued) There is no evidence that procaine benzylpenicillin is teratogenic. It may Congenital syphilis in children be used during pregnancy. £ 2 years 50000IU/kg (maximum 1.5 million IU) Adverse effects i.m. every 24 hours for 10 days. Hypersensitivity reactions are common, ranging in severity from skin rashes to Contraindications immediate anaphylaxis. Known hypersensitivity to penicillins or Pain and sterile inflammation can occur cefalosporins. at the site of intramuscular injection. Accidental injection into a peripheral Precautions nerve causes severe pain and Facilities should be available for treating dysfunction. anaphylaxis whenever penicillins are used. Patients should be questioned Interstitial nephritis has been reported. carefully about previous allergic reactions before the first dose is Neutropenia and thrombocytopenia are administered. If a skin rash develops rare. during treatment, the patient should be transferred to a different class of Storage antimicrobial. Powder for injection should be stored in vials at 2–8 °C.

Cefalexin Capsule, 250mg, 500mg

• urinary tract infections General information • pyomyositis, cellulitis and erysipelas, Cefalexin is a first-generation cefalo- together with cefazolin sporin that is active against many Gram- • localized purulent skin lesions and positive aerobic cocci but has limited impetigo activity against Gram-negative bacteria. • osteomyelitis and septic arthritis due It is rapidly and completely absorbed to Staphylococcus aureus in adults, from the gastrointestinal tract. Its plasma together with cefazolin half-life is 0.5–1.2 hours. It is excreted in • osteomyelitis and septic arthritis due the urine as unchanged drug. to Staphylococcus aureus in children > 5 years, together with ceftriaxone or cefazolin. Clinical information Dosage and administration Uses Acute pharyngitis and acute cervical Treatment of: adenitis in patients allergic to • acute pharyngitis and acute cervi- penicillins cal adenitis in patients allergic to Adults: 500mg orally every 6–8 hours for penicillins 10 days.

106 Drugs

Children: 15mg/kg (maximum 500mg) weeks, following initial therapy with orally every 6–8 hours for 10 days. cefazolin 1–2g i.v. or i.m. every 8 hours. Urinary tract infections Children > 5 years: 25mg/kg (maximum Women: 500mg orally every 8 hours for 500mg) orally every 6 hours to complete 5 days (for uncomplicated infections). the treatment course of 3–4 weeks, fol- lowing initial therapy with either ceftri- Men: 500mg orally every 8 hours for at axone 50–75 mg/kg (maximum 1 g) i.v. least 14 days. or i.m. every 24 hours or cefazolin 15 Children: 12.5mg/kg (maximum 500 mg/kg (maximum 1g) i.v. or i.m. every mg) orally every 6 hours for 5–10 days. 8 hours for 4–6 days (or until clinical improvement occurs). Localized purulent skin lesions and impetigo Septic arthritis due to Staphylo- Adults: 500mg orally every 6 hours for coccus aureus in adults and children 5–7 days. > 5 years Adults: 1–2 g orally every 6 hours to Children: 12.5–25mg/kg (maximum complete the treatment course of 2–3 500mg) orally every 6 hours for 5–7 weeks, following initial therapy with days. cefazolin 1–2 g i.v. or i.m. every 8 hours. Cellulitis and erysipelas Children > 5 years: 25 mg/kg (maximum Adults: 500mg orally every 6 hours to 500 mg) orally every 6 hours to complete complete the treatment course of 7–10 the treatment course of 2–3 weeks, fol- days, following initial therapy with lowing initial therapy with either cef- cefazolin 1–2g i.v. or i.m. every 8 hours. triaxone 50–75 mg/kg (maximum 1 g) i.v. or i.m. every 24 hours or cefazolin Children: 12.5–25mg/kg (maximum 15 mg/kg (maximum 1 g) i.v. or i.m. 500mg) orally every 6 hours to complete every 8 hours for 4–6 days (or until the treatment course of 7–10 days, clinical improvement occurs). following initial therapy with cefazolin 15mg/kg (maximum 2g) i.v. or i.m. In some cases, especially in adults, every 8 hours. repeated aspiration or surgical washout of the joint may be necessary. Pyomyositis Adults: 500mg orally every 6 hours to Contraindications complete the treatment course of 5–10 Known hypersensitivity to other b- days, following initial therapy with lactamase antimicrobials. cefazolin 1–2g i.v. or i.m. every 8 hours. Children: 12.5–25mg/kg (maximum Precautions 500mg) orally every 6 hours to complete Transient increases in liver enzymes may the treatment course of 5–10 days, fol- occur. lowing initial therapy with cefazolin 15mg/kg (maximum 2g) i.v. or i.m. Use in pregnancy every 8 hours. There is no evidence that cefalexin is teratogenic. It may be used during Osteomyelitis due to Staphylococcus pregnancy. aureus in adults and children > 5 years Adults: 1–2g orally every 6 hours to complete the treatment course of 4–6

107 WHO Model Prescribing Information — Drugs used in bacterial infections

Cefalexin (continued) difficile occurs. When this is suspected, treatment should be immediately Adverse effects discontinued. Hypersensitivity reactions are the most Reversible cholestatic jaundice has been common adverse effects. Skin rashes are reported. relatively frequent, while urticaria, bron- chospasm and anaphylaxis are uncom- Storage mon. Nausea, vomiting and diarrhoea Capsules should be stored in tightly have been reported. closed containers. Rarely, antimicrobial-associated pseudo- membranous colitis due to Clostridium

Cefazolin Powder for injection, 500mg in vial

Prophylaxis in clean surgery. General information Prophylaxis in contaminated surgery, Cefazolin is a first-generation cefalo- together with metronidazole. sporin that is active against many Gram- positive aerobic cocci but has limited Dosage and administration activity against Gram-negative bacteria. Pneumonia due to Staphylococcus It is poorly absorbed from the gastroin- aureus in adults and children testinal tract and must be administered > 5 years parenterally. Its plasma half-life is 1.2–2.2 Adults: 1–2g i.v. or i.m. every 8 hours for hours. It is excreted as unchanged drug 10–14 days. in the urine. Children > 5 years: 15–25mg/kg (maxi- mum 2g) i.v. or i.m. every 8 hours for Clinical information 10–14 days. Uses Cellulitis and erysipelas Treatment of: Adults: 1–2g i.v. or i.m. every 8 hours for • pneumonia due to Staphylococcus 7–10 days (once clinical improvement aureus in adults and children > 5 years occurs, cefalexin 500mg orally every 6 • cellulitis, erysipelas and pyomyositis, hours may be substituted). together with cefalexin Children: 15mg/kg (maximum 2g) i.v. • osteomyelitis and septic arthritis due or i.m. every 8 hours for 7–10 days (once to Staphylococcus aureus in adults and clinical improvement occurs, cefalexin children > 5 years, together with 12.5–25mg/kg (maximum 500mg) cefalexin orally every 6 hours may be substituted). • septicaemia (initial empirical therapy) in adults and children > 5 years, Pyomyositis together with gentamicin. Adults: 1–2g i.v. or i.m. every 8 hours for 5–10 days (once clinical improvement

108 Drugs occurs, cefalexin 500mg orally every 6 either gentamicin 5–7mg/kg i.v. every 24 hours may be substituted). hours or gentamicin 1.5mg/kg i.v. or i.m. every 8 hours. Children: 15mg/kg (maximum 2g) i.v. or i.m. every 8 hours for 5–10 days (once Prophylaxis in clean surgery clinical improvement occurs, cefalexin Adults and children: 1g i.v. at induction 12.5–25mg/kg (maximum 500mg) of anaesthesia (if the operation is pro- orally every 6 hours may be substituted). longed beyond 3–4 hours a further 1-g dose should be administered). Osteomyelitis due to Staphylococcus aureus in adults and children Prophylaxis in contaminated surgery > 5 years Adults and children: 1 g i.v., together Adults: 1–2g i.v. or i.m. every 8 hours for with metronidazole 500 mg i.v. at in- 4–6 weeks (if the duration of parenteral duction of anaesthesia (if the opera- therapy is less than 4–6 weeks, the treat- tion is prolonged beyond 3–4 hours, a ment course should be completed with further 1-g dose of cefazolin should be cefalexin 1–2g orally every 6 hours). administered).

Children > 5 years: 15mg/kg (maximum Contraindications 1g) i.v. or i.m. every 8 hours for 4–6 days b (or until clinical improvement occurs), Known hypersensitivity to other - followed by cefalexin 25mg/kg (maxi- lactamase antimicrobials. mum 500mg) orally every 6 hours to complete the treatment course of 3–4 Precautions weeks. Transient increases in liver enzymes may occur. Septic arthritis due to Staphylo- coccus aureus in adults and children Use in pregnancy > 5 years There is no evidence that cefazolin is Adults: 1–2 g i.v. or i.m. every 8 hours for teratogenic. It may be used during 2–3 weeks (if the duration of parenteral pregnancy. therapy is less than 2–3 weeks, the treat- ment course should be completed with Adverse effects cefalexin 1–2 g orally every 6 hours). Hypersensitivity reactions are the most Children > 5 years: 15 mg/kg (maximum common adverse effects. Skin rashes 1 g) i.v. or i.m. every 8 hours for 4–6 are relatively frequent, while urticaria, days (or until clinical improvement bronchospasm and anaphylaxis are occurs), followed by cefalexin 25 mg/kg uncommon. Nausea, vomiting and (maximum 500mg) orally every 6 hours diarrhoea have been reported. Rarely, to complete the treatment course of 2–3 antimicrobial-associated pseudomem- weeks. branous colitis due to Clostridium difficile occurs. When this is suspected, treatment In some cases, especially in adults, should be immediately discontinued. repeated aspiration or surgical washout of the joint may be necessary. Reversible cholestatic jaundice has been reported. Initial empirical therapy for septicaemia in adults and children Storage > 5 years Powder for injection should be stored in 1–2g i.v. every 8 hours, together with tightly closed containers.

109 WHO Model Prescribing Information — Drugs used in bacterial infections

Cefotaxime Powder for injection, 500 mg in vial

Dosage and administration General information Severe croup (laryngotracheo- Cefotaxime is a semisynthetic third- bronchitis) in neonates generation cefalosporin. It is bacteri- 50 mg/kg i.v. or i.m. every 8 hours for 5 cidal against Gram-negative organisms, days. including Pseudomonas aeruginosa, and Epiglottitis in neonates certain Gram-positive bacteria. After Neonates aged 1–2 months: 50 mg/kg i.v. intramuscular administration, it is or i.m. every 8 hours for 5 days, supple- widely distributed throughout the body mented for the first 4 days by rifampicin and is excreted primarily unchanged in 20 mg/kg (maximum 600 mg) orally the urine. every 24 hours. Neonates < 1 month: 50 mg/kg i.v. or i.m. Clinical information every 8 hours for 5 days, supplemented Uses for the first 4 days by rifampicin 10 mg/ kg (maximum 300 mg) orally every 24 Treatment of: hours. • severe croup (laryngotracheobronchi- tis) in neonates Neonatal pneumonia • epiglottitis in neonates, together with 50 mg/kg i.v. every 12 hours for at least rifampicin 5 days. • neonatal pneumonia Cefotaxime is often administered in • osteomyelitis due to Haemophilus combination with ampicillin (50 mg/kg influenzae or unknown pathogen in i.v. every 8 hours for at least 5 days), neonates, together with cloxacillin because of problems of resistance in + and amoxicillin clavulanic acid Gram-negative enteric bacteria and the • osteomyelitis due to Salmonella spp. possibility of Listeria spp. infections in in neonates, together with cloxacil- neonates. lin and either sulfamethoxazole + trimethoprim or amoxicillin or cipro- Osteomyelitis due to Haemophilus floxacin influenzae or unknown pathogen in • septic arthritis (initial empirical neonates therapy) and osteomyelitis and septic 50–75 mg/kg (maximum 2 g) i.v. every 8 arthritis due to Staphylococcus aureus in hours, together with cloxacillin 25–50 neonates, together with cloxacillin mg/kg (maximum 2 g) i.v. or i.m. every • neonatal gonococcal conjunctivitis 4–6 hours for 4–6 days (or until clinical • neonatal meningitis due to unknown improvement occurs), followed by pathogen, together with ampicillin amoxicillin 15 mg/kg + clavulanic acid • septicaemia (initial empirical therapy) (maximum 500 mg) orally every 8 hours in neonates, together with cloxacillin. to complete the treatment course of 3–4 weeks.

110 Drugs

Osteomyelitis due to Staphylococcus Neonatal meningitis due to unknown aureus in neonates pathogen 50–75 mg/kg (maximum 2 g) i.v. every 8 50 mg/kg (maximum 2 g) i.v. every 12 hours, together with cloxacillin 25–50 hours, together with ampicillin 50 mg/kg (maximum 2 g) i.v. or i.m. every mg/kg (maximum 2 g) i.v. every 8 hours 4–6 hours for 4–6 days (or until clinical (neonates < 7 days: 50 mg/kg (maximum improvement occurs), followed by clo- 2 g) i.v. every 12 hours) for a total of 7–10 xacillin 12.5 mg/kg (maximum 500 mg) days. orally every 6 hours to complete the treat- ment course of 3–4 weeks. Initial empirical therapy for septi- caemia in neonates Osteomyelitis due to Salmonella 50–75 mg/kg (maximum 2 g) i.v. every 8 spp. in neonates hours, together with cloxacillin 50 50–75 mg/kg (maximum 2 g) i.v. every 8 mg/kg (maximum 2 g) every 4–6 hours. hours, together with cloxacillin 25–50 mg/kg (maximum 2 g) i.v. or i.m. every Contraindications 4–6 hours for 4–6 days (or until clinical Known hypersensitivity to other b- improvement occurs), followed by either lactam antibiotics. sulfamethoxazole 20 mg/kg + trimetho- prim 4 mg/kg (maximum 800 mg + 160 Precautions mg) orally every 12 hours or amoxicillin Blood concentrations of liver enzymes 7.5–15 mg/kg (maximum 1 g) orally may rise transiently. every 8 hours or ciprofloxacin 10–15 mg/kg (maximum 500 mg) orally every Use in pregnancy 12 hours to complete the treatment There is no evidence that cefotaxime course of 6 weeks. is teratogenic. It may be used during Initial empirical therapy for septic pregnancy. arthritis in neonates 50–75 mg/kg (maximum 2 g) i.v. every 8 Adverse effects hours, together with cloxacillin 25–50 Hypersensitivity reactions are the most mg/kg (maximum 2 g) i.v. or i.m. every common adverse effects. Skin rashes are 6 hours. relatively frequent, while urticaria, bronchospasm and anaphylaxis are Septic arthritis due to Staphylo- uncommon. Nausea, vomiting and coccus aureus in neonates diarrhoea have been reported. Rarely, 50–75 mg/kg (maximum 2 g) i.v. every 8 antimicrobial-associated pseudomem- hours, together with cloxacillin 25–50 branous colitis due to Clostridium difficile mg/kg (maximum 2 g) i.v. or i.m. every occurs. When this is suspected, treatment 4–6 hours for 4–6 days (or until clinical should be immediately discontinued. improvement occurs), followed by clo- xacillin 12.5 mg/kg (maximum 500 mg) Reversible cholestatic jaundice has been orally every 6 hours to complete the treat- reported. ment course of 2–3 weeks. Storage Neonatal gonococcal conjunctivitis Powder for injection should be stored in 50 mg/kg (maximum 2 g) i.v. in a single tightly closed containers, protected from dose. light.

111 WHO Model Prescribing Information — Drugs used in bacterial infections

Ceftazidime Powder for injection, 250mg (as pentahydrate) in vial

thoxazole 1600mg + trimethoprim 320 General information mg orally or i.v. every 12 hours or doxy- Ceftazidime is a semisynthetic third- cycline 100mg orally or i.v. every 12 generation cefalosporin that is bacteri- hours. cidal against a wide range of Gram- Children > 8 years: 50mg/kg (maximum negative bacteria, including Pseudomonas 2g) i.v. every 8 hours for at least 14 days, aeruginosa, and some Gram-positive bac- supplemented by either sulfamethoxa- teria. After intramuscular administration, zole 40mg/kg + trimethoprim 8mg/ the drug is widely distributed through- kg (maximum 1600mg + 320mg) orally out the body and is excreted primarily or i.v. every 12 hours or doxycycline unchanged in the urine. 2mg/kg (maximum 100mg) orally or i.v. every 12 hours. Clinical information Children £ 8 years: 50mg/kg (maximum 2g) i.v. every 8 hours for at least 14 days, Uses supplemented by sulfamethoxazole 40 Treatment of: mg/kg + trimethoprim 8mg/kg (maxi- • nosocomial pneumonia, together with mum 1600mg + 320mg) orally or i.v. gentamicin or ciprofloxacin every 12 hours. • melioidosis, together with sulfa- After the initial intensive therapy, eradi- methoxazole + trimethoprim or doxy- cation of any secondary infection is rec- cycline. ommended with oral sulfamethoxazole + trimethoprim or doxycycline for at Dosage and administration least 3 months. Nosocomial pneumonia Adults: 1 g i.v. every 8 hours for 7 days, Contraindications supplemented by either gentamicin 5–7 Known hypersensitivity to other b- mg/kg i.v. daily in divided doses or lactamase antimicrobials. ciprofloxacin 500 mg i.v. every 12 hours. Children: 25 mg/kg (maximum 1 g) i.v. Precautions every 8 hours for 7 days, supplemented Blood concentrations of liver enzymes by either gentamicin 7.5mg/kg daily in 1–3 may rise transiently. divided doses or ciprofloxacin 10 mg/kg (maximum 300 mg) i.v. every 12 hours. Use in pregnancy There is no evidence that ceftazidime In hospitals with a high prevalence of is teratogenic. It may be used during meticillin-resistant Staphylococcus aureus, pregnancy. vancomycin 1 g (children: 20 mg/kg; maximum 1 g) i.v. should be added to the Adverse effects above regimens. Hypersensitivity reactions are the most Melioidosis common adverse effects. Skin rashes Adults: 2g i.v. every 8 hours for at least are relatively frequent, while urticaria, 14 days, supplemented by either sulfame- bronchospasm and anaphylaxis are

112 Drugs uncommon. Nausea, vomiting and Reversible cholestatic jaundice has been diarrhoea have been reported. Rarely, reported. antimicrobial-associated pseudomem- branous colitis due to Clostridium difficile Storage occurs. When this is suspected, treatment Powder for injection should be stored in should be immediately discontinued. tightly closed containers, protected from light.

Ceftriaxone Powder for injection, 250mg (as sodium salt) in vial

influenzae or unknown pathogen in General information children aged from 2 months to 5 Ceftriaxone is a third-generation cefalo- years, together with cloxacillin and + sporin derived from Cephalosporium acre- amoxicillin clavulanic acid monium. It is highly active against • osteomyelitis due to Salmonella spp. in Gram-negative cocci and bacilli. Like children aged from 2 months to 5 benzylpenicillin, it has a b-lactam ring. years, together with cloxacillin and either sulfamethoxazole + trimetho- After intramuscular administration, cef- prim or amoxicillin or ciprofloxacin triaxone is distributed widely through- • septic arthritis (initial empirical out the body. It has a relatively long therapy), together with cloxacillin plasma half-life of about 8 hours and is • septic arthritis due to Staphylococcus excreted unchanged in both urine and bile. aureus in children, together with cloxacillin or cefalexin • disseminated gonococcal infections, Clinical information uncomplicated anogenital gonococcal Uses infections and chancroid in adults • gonococcal conjunctivitis in adults Treatment of: and neonates • acute mastoiditis • pelvic inflammatory disease in adults • epiglottitis in adults and children > 2 (ambulatory patients), together with months doxycycline and metronidazole • severe croup (laryngotracheobronchi- • moderate and severe pelvic inflamma- tis) in children > 2 months tory disease in adults (hospitalized • pneumonia in adults and children > 5 patients), together with doxycycline years and very severe pneumonia in • meningitis (initial empirical therapy), children aged from 2 months to 5 years meningitis due to Haemophilus in- • atypical pneumonia in adults and chil- fluenzae and meningitis due to dren > 5 years, together with eryth- benzylpenicillin-susceptible Strepto- romycin coccus pneumoniae • acute pyelonephritis, together with • meningitis due to benzylpenicillin- ampicillin resistant and ceftriaxone/cefotaxime- • osteomyelitis due to Staphylococcus resistant Streptococcus pneumoniae, aureus in children, together with together with vancomycin and rifam- cloxacillin or cefalexin picin • osteomyelitis due to Haemophilus • Lyme disease (late stage) in adults

113 WHO Model Prescribing Information — Drugs used in bacterial infections

Ceftriaxone (continued) Very severe pneumonia in children aged from 2 months to 5 years • septicaemia (initial empirical therapy) 50mg/kg (maximum 1g) i.v. or i.m. in children aged from 2 months to 5 every 24 hours for at least 5 days. years, together with cloxacillin. Acute pyelonephritis Dosage and administration Adults: 1g i.v. or i.m. every 24 hours for Ceftriaxone must be administered par- 14 days, supplemented for up to 14 days enterally. Intravenous formulations of by ampicillin 1–2g i.v. or i.m. every 6 ceftriaxone should be administered over hours. at least 2 minutes. Children: 50mg/kg (maximum 1g) i.v. Acute mastoiditis or i.m. every 24 hours for 14 days, Adults: 1g i.v. or i.m. every 12 hours for supplemented for up to 14 days by 10 days. ampicillin 50mg/kg (maximum 2g) i.v. or i.m. every 6 hours. Children: 50mg/kg (maximum 1g) i.v. or i.m. every 12 hours for 10 days. Osteomyelitis due to Staphylococcus aureus in children Severe croup (laryngotracheobron- Children > 5 years: 50–75mg/kg (maxi- chitis) in children > 2 months mum 1g) i.v. or i.m. every 24 hours for 100 mg/kg (maximum 2 g) i.v. or i.m. 4–6 days (or until clinical improvement every 24 hours for 5 days. occurs), followed by either cloxacillin 25 mg/kg (maximum 500mg) or cefalexin Epiglottitis in adults and children 25mg/kg (maximum 500mg) orally > 2 months every 6 hours to complete the treatment Adults: 2g i.v. or i.m. every 24 hours for course of 3–4 weeks. 5 days. Children aged from 2 months to 5 years: Children > 2 months: 100mg/kg (maxi- 50–75mg/kg (maximum 1g) i.v. or i.m. mum 2g) i.v. or i.m. every 24 hours for 5 every 24 hours, together with cloxacillin days. 25–50mg/kg (maximum 2g) i.v. or i.m. In young children, consideration should every 4–6 hours for 4–6 days (or until be given to vaccination against Haemo- clinical improvement occurs), followed philus influenzae type b. by cloxacillin 12.5mg/kg (maximum 500 mg) orally every 6 hours to complete the Pneumonia in adults and children treatment course of 3–4 weeks. > 5 years Hospitalized patients Osteomyelitis due to Haemophilus Adults: 1g i.v. or i.m. every 12–24 hours influenzae or unknown pathogen in for 7 days. children aged from 2 months to 5 years Children > 5 years: 50mg/kg (maximum 50–75mg/kg (maximum 1g) i.v. or i.m. 1g) i.v. or i.m. every 12–24 hours for 7 every 24 hours, together with cloxacillin days. 25–50mg/kg (maximum 2g) i.v. or i.m. every 4–6 hours for 4–6 days (or until Patients with atypical pneumonia clinical improvement occurs), followed should also receive erythromycin 1g by amoxicillin 15mg/kg + clavulanic (children: 10mg/kg; maximum 1g) i.v. acid (maximum 500 mg) orally every 8 every 6 hours for 14 days. hours to complete the treatment course of 3–4 weeks.

114 Drugs

Osteomyelitis due to Salmonella spp. Uncomplicated anogenital gono- in children aged from 2 months to coccal infections and gonococcal 5 years conjunctivitis in adults 50–75mg/kg (maximum 1g) i.v. or i.m. 250mg i.m. in a single dose. every 24 hours, together with cloxacillin All patients with gonorrhoea should be 25–50mg/kg (maximum 2g) i.v. or i.m. treated concurrently for chlamydial in- every 4–6 hours for 4–6 days (or until fection unless microbiological facilities clinical improvement occurs), followed exist to exclude the latter diagnosis. + by either sulfamethoxazole 20mg/kg Sexual partners should be treated simul- trimethoprim 4mg/kg (maximum 800 taneously. mg + 160mg) orally every 12 hours or amoxicillin 7.5–15mg/kg (maximum Disseminated gonococcal infec- 1g) orally every 8 hours or ciprofloxacin tions in adults 10–15mg/kg (maximum 500mg) orally 1g i.m. every 24 hours for 7 days. every 12 hours to complete the treatment If there is evidence of meningeal or course of 6 weeks. endocardial involvement, treatment should be extended to 2 weeks and 4 Initial empirical therapy for septic weeks, respectively. arthritis Adults: 1–2g i.v. or i.m. every 24 hours, All patients with gonorrhoea should be together with cloxacillin 2g i.v. or i.m. treated concurrently for chlamydial in- every 6 hours. fection unless microbiological facilities exist to exclude the latter diagnosis. Children ≥2 months: 25–50mg/kg Sexual partners should be treated simul- (maximum 2g) i.v. or i.m. every 24 hours, taneously. together with cloxacillin 25–50mg/kg (maximum 2g) i.v. or i.m. every 6 hours. Neonatal gonococcal conjunctivitis 50mg/kg (maximum 125mg) i.m. in a Septic arthritis due to Staphylo- single dose. coccus aureus in children Chancroid in adults Children > 5 years: 50–75 mg/kg (maxi- mum 1 g) i.v. or i.m. every 24 hours for 250mg i.m. in a single dose. (Longer 4–6 days (or until clinical improvement treatment courses may be necessary in occurs), followed by either cloxacillin 25 immunocompromised patients.) mg/kg (maximum 500 mg) or cefalexin Pelvic inflammatory disease in adults 25 mg/kg (maximum 500 mg) orally Ambulatory patients every 6 hours to complete the treatment 250mg i.m. in a single dose, followed by course of 2–3 weeks. doxycycline 100mg orally every 12 Children aged from 2 months to 5 years: hours and metronidazole 400–500mg 50–75 mg/kg (maximum 1 g) i.v. or i.m. orally every 8 hours for 10 days. every 24 hours, together with cloxacillin Hospitalized patients with moderate or 25–50 mg/kg (maximum 2 g) i.v. or i.m. severe disease every 4–6 hours for 4–6 days (or until 250mg i.m. every 12 hours for at least 4 clinical improvement occurs), followed days (or for 48 hours after clinical impro- by cloxacillin 12.5 mg/kg (maximum 500 vement), followed by doxycycline 100 mg) orally every 6 hours to complete the mg orally every 12 hours for 10–14 days. treatment course of 2–3 weeks. Initial empirical therapy for In some cases repeated aspiration or sur- meningitis gical washout of the joint may also be Adults: 2g i.v. or i.m. daily in one or two necessary. divided doses for up to 14 days.

115 WHO Model Prescribing Information — Drugs used in bacterial infections

Ceftriaxone (continued) Children: 50mg/kg (maximum 2g) i.v. or i.m. every 12 hours for 7–10 days. Children: 50–100mg/kg (maximum 2g) i.v. or i.m. daily in one or two divided Lyme disease (late stage) in adults doses for up to 14 days. 2g i.v. or i.m. every 24 hours for 14–21 days. Meningitis due to Streptococcus pneumoniae Patients with neurological involvement Strains susceptible to benzylpenicillin usually require treatment for 21 days. (MIC £ 0.06 mg/l) Initial empirical therapy for septicae- Adults: 2 g i.v. or i.m. daily in one or two mia in children aged from 2 months divided doses for 10–14 days. to 5 years Children: 50–100 mg/kg (maximum 2 g) 50mg/kg (maximum 2g) i.v. or i.m. i.v. or i.m. daily in one or two divided every 24 hours, together with cloxacillin doses for 10–14 days. 50mg/kg (maximum 2g) i.v. every 4–6 hours. Patients who are severely ill may require treatment for up to 3 weeks. Contraindications Strains showing intermediate resistance Known hypersensitivity to other b- to benzylpenicillin (MIC = 0.125– lactam antimicrobials. 1.0mg/l) Adults: 2g i.v. or i.m. daily in one or two Precautions divided doses for 10–14 days. Blood concentrations of liver enzymes may rise transiently. Children: 50–100mg/kg (maximum 2g) i.v. or i.m. daily in one or two divided Use in pregnancy doses for 10–14 days. There is no evidence that ceftriaxone is teratogenic. It may be used during preg- Strains resistant to benzylpenicillin nancy. (MIC >1.0mg/l) or ceftriaxone/ cefotaxime (MIC ≥1.0mg/l) Adverse effects Adults: 2g i.v. or i.m. every 12 hours for at least 14 days, supplemented by Hypersensitivity reactions are the most vancomycin 1g i.v. every 12 hours and common adverse effects. Skin rashes are rifampicin 600mg orally every 24 hours. relatively frequent, while urticaria, bronchospasm and anaphylaxis are Children: 50–100mg/kg (maximum 2g) uncommon. Nausea, vomiting and i.v. or i.m. every 12 hours for at least 14 diarrhoea have been reported. Rarely, days, supplemented by vancomycin 20 antimicrobial-associated pseudomem- mg/kg (maximum 1g) i.v. every 6 hours branous colitis due to Clostridium difficile and rifampicin 20mg/kg (maximum 600 occurs. When this is suspected, treatment mg) orally every 24 hours. should be immediately discontinued. Patients should be referred to a specialist. Reversible cholestatic jaundice has been reported. Meningitis due to Haemophilus influenzae Storage Adults: 2g i.v. or i.m. every 12 hours for Powder for injection should be stored in 7–10 days. tightly closed containers, protected from light.

116 Drugs

Cefuroxime Powder for injection, 250 mg

Precautions General information Blood concentrations of liver enzymes Cefuroxime is a semisynthetic second- may rise transiently. generation cefalosporin. It is bactericidal against certain Gram-negative bacteria. Use in pregnancy After intramuscular administration, it is There is no evidence that cefuroxime is widely distributed throughout the body teratogenic. It may be used during and is excreted primarily unchanged in pregnancy. the urine. Adverse effects Hypersensitivity reactions are the most Clinical information common adverse effects. Skin rashes are relatively frequent, while urticaria, Uses bronchospasm and anaphylaxis are Treatment of pneumonia in adults and uncommon. Nausea, vomiting and children > 5 years. diarrhoea have been reported. Rarely, antimicrobial-associated pseudomem- Dosage and administration branous colitis due to Clostridium difficile Adults: 1.0–1.5 g i.v. every 6–8 hours for occurs. When this is suspected, treatment 7 days. should be immediately discontinued. Children > 5 years: 50–60 mg/kg (maxi- Reversible cholestatic jaundice has been mum 1.5 g) i.v. every 6–8 hours for 7 days. reported.

Contraindications Storage Known hypersensitivity to other b- Powder for injection should be stored in lactamase antimicrobials. tightly closed containers, protected from light.

Chloramphenicol Capsule, 250mg Oral suspension, 150mg (as palmitate)/5ml Powder for injection, 1g (as sodium succinate) in vial Oily suspension, 0.5g (as sodium succinate)/ml in 2-ml ampoule

against many anaerobic bacteria. It is General information primarily bacteriostatic and inhibits Chloramphenicol is a synthetic broad- bacterial protein synthesis. spectrum antimicrobial which is active Chloramphenicol is rapidly absorbed against most Gram-negative and Gram- from the gastrointestinal tract, is positive aerobic bacteria. It is also active metabolized in the liver, and is readily

117 WHO Model Prescribing Information — Drugs used in bacterial infections

Chloramphenicol (continued) The oily suspension has been found to be helpful in situations of catastrophic distributed in most tissues and epidemics of meningococcal meningitis body fluids including the cerebrospinal occurring mainly in sub-Saharan Africa, fluid. The plasma half-life is 1.5– during which the medical services are 4.0 hours. It is excreted in the urine as overwhelmed by the epidemic. For this metabolites. reason, the product should be reserved for use in epidemics of meningococcal Chloramphenicol crosses the placenta meningitis when the overwhelming and is excreted in breast milk. scale of the epidemic precludes any other form of antimicrobial therapy.

Clinical information Dosage and administration Uses The dosage should be adjusted where Treatment of: plasma monitoring is feasible, to • severe infections due to susceptible maintain plasma concentrations at 5– bacteria when other less toxic 20mg/ml. antimicrobials are ineffective or The dosage should be reduced in pa- contraindicated tients with renal or hepatic impairment. • acute mastoiditis • epiglottitis in adults and children > 2 Acute mastoiditis months, together with rifampicin Adults: 1g i.v. or i.m. every 6–8 hours for • severe croup (laryngotracheobronchi- 10–14 days. tis) in children > 2 months • chronic suppurative lung disease in Children: 25mg/kg (maximum 750mg) children i.v. or i.m. every 6–8 hours for 10–14 • pneumonia in adults and children > 5 days. years, very severe pneumonia in chil- Epiglottitis in adults and children dren aged from 2 months to 5 years > 2 months and neonatal pneumonia Adults: 1 g i.v. or i.m. every 6–8 hours • atypical pneumonia in adults and for 5 days, supplemented by rifampicin children > 5 years, together with 600 mg orally every 24 hours for the first erythromycin 4 days. • typhoid and paratyphoid fever and infectious enteritis due to Salmonella Children > 2 months: 25 mg/kg (maxi- enteritidis mum 1 g) i.v. or i.m. every 6 hours for • granuloma inguinale in adults 5 days, supplemented by rifampicin • meningitis (initial empirical therapy), 20 mg/kg (maximum 600mg) orally every meningitis due to Neisseria meningi- 24 hours for the first 4 days. tidis, and brain abscess, together with In young children, consideration should benzylpenicillin be given to vaccination against Haemo- • meningitis due to Haemophilus influen- philus influenzae serotype b. zae • relapsing fever, tularaemia, plague Severe croup (laryngotracheobron- and rickettsial infections chitis) in children > 2 months • septicaemia (initial empirical therapy) 25 mg/kg (maximum 1 g) i.v. or i.m. in adults and children > 5 years, every 6 hours for 5 days. together with gentamicin.

118 Drugs

Chronic suppurative lung disease substituted), supplemented by benzyl- in children penicillin 3–4 million IU i.v. or i.m. every 25mg/kg (maximum 1g) i.v. or i.m. 4 hours. every 6 hours for 5 days. Children: 25mg/kg (maximum 1g) i.v. Pneumonia in adults and children every 6 hours for up to 14 days (once >5 years clinical improvement occurs, 25mg/kg Hospitalized patients (maximum 750mg) orally every 6 hours Adults: 1g i.v. every 6 hours for 7 days. may be substituted), supplemented by benzylpenicillin 100000IU/kg (maxi- Children: 25mg/kg (maximum 750mg) mum 4 million IU) i.v. or i.m. every 4 i.v. every 6 hours for 7 days. hours. Patients with atypical pneumonia Meningitis due to Neisseria should also receive erythromycin 1g meningitidis (children: 10mg/kg; maximum 1g) i.v. Adults: oily suspension 100mg/kg every 6 hours for 14 days. (maximum 3g) i.m. every 24 hours for Very severe pneumonia in children up to 14 days (once clinical improvement aged from 2 months to 5 years occurs, chloramphenicol 500–750mg 25mg/kg (maximum 750mg) i.v. or i.m. orally every 6 hours may be substituted), every 6 hours for at least 10 days (once supplemented by benzylpenicillin 3–4 clinical improvement occurs, oral dosage million IU i.v. or i.m. every 4 hours. forms may be substituted). Children: oily suspension 25mg/kg Pneumonia in neonates (maximum 500mg) i.m. every 24 hours for up to 14 days (once clinical improve- 25mg/kg (maximum 750mg) i.v. every ment occurs, chloramphenicol 25mg/kg 12 hours for at least 5 days (contraindi- (maximum 750mg) orally every 6 hours cated in premature infants or neonates may be substituted), supplemented by <7 days). benzylpenicillin 100000IU/kg (maxi- Chloramphenicol should be used for this mum 4 million IU) i.v. or i.m. every 4 indication only when no alternatives are hours. available. Meningitis due to Haemophilus Typhoid and paratyphoid fever and influenzae infectious enteritis due to Salmo- Adults: 1g i.v. every 6 hours for 7–10 nella enteritidis days. Adults: 1g orally every 6 hours for 10– Children: 25mg/kg (maximum 1g) i.v. 14 days. every 6 hours for 7–10 days. Children: 25mg/kg (maximum 750mg) Chloramphenicol should only be used if orally every 6 hours for 10–14 days. the isolate is known to be susceptible. Granuloma inguinale in adults Prophylaxis with rifampicin 600mg 500mg orally every 6 hours for 3 weeks (neonates <1 month: 5mg/kg (maxi- (or until the lesion has completely healed). mum 300mg); children ≥1 month: Initial empirical therapy for meningitis 10mg/kg (maximum 600mg)) orally Adults: 1g i.v. every 6 hours for up to 14 every 24 hours for 4 days should be con- days (once clinical improvement occurs, sidered for patients and their close con- 500–750mg orally every 6 hours may be tacts, especially children under 5 years.

119 WHO Model Prescribing Information — Drugs used in bacterial infections

Chloramphenicol (continued) Contraindications • Because of its unpredictable toxicity, Brain abscess chloramphenicol should never be used Adults: 1g i.v. every 6 hours, together in diseases which are safely and effec- with benzylpenicillin 3–4 million IU i.v. tively treated by other antimicrobials. or i.m. every 4–6 hours. • Known hypersensitivity to chloram- Children: 25mg/kg (maximum 750mg) phenicol. i.v. every 6 hours, together with ben- • Neonates <1 week and premature zylpenicillin 100000IU/kg (maximum 3 infants. million IU) i.v. or i.m. every 4–6 hours. • Third trimester of pregnancy. The duration of treatment depends on Precautions the clinical response and radiological When facilities are available, the blood evidence of resolution of the abscess. count should be monitored. Because of the narrow margin between effective Relapsing fever therapeutic and toxic dosages of chlor- Adults: 500mg orally in a single dose. amphenicol, the plasma concentrations Children: 25mg/kg (maximum 750mg) should be monitored whenever possible. orally in a single dose. Use in pregnancy Tularaemia Safe use in early pregnancy has not been Adults: 1 g i.v. every 6 hours for 7 days. established. Chloramphenicol should be Children: 25 mg/kg (maximum 1 g) i.v. administered only when the need of the every 6 hours for 7 days. mother outweighs any potential risk to the fetus. Plague Adults: 500mg orally or i.v. every 6 Adverse effects hours for 7–10 days. The most serious adverse effect of chlor- amphenicol is bone-marrow depression. Children: 25mg/kg (maximum 750mg) Irreversible aplastic anaemia, which is orally or i.v. every 6 hours for 7–10 days. fatal in 50% of cases, can occur after a Rickettsial infections single dose. The risk of reversible aplas- Adults: 500mg orally or i.v. every 6 tic anaemia increases with prolonged hours for 7–10 days (or for 48 hours after therapy. resolution of fever). Other haematological abnormalities Children: 15mg/kg (maximum 500mg) including leukopenia, thrombocytope- orally or i.v. every 6 hours for 7–10 days nia and impaired synthesis of haemoglo- (or for 48 hours after resolution of fever). bin are dose-related and usually reversible. Initial empirical therapy for septicae- mia in adults and children > 5 years Grey baby syndrome characterized by 750mg i.v. every 6 hours, together with vomiting, greenish diarrhoea, abdominal either gentamicin 5–7mg/kg i.v. every 24 distension, hypothermia, flaccidity and hours or gentamicin 1.5mg/kg i.v. or i.m. respiratory and cardiovascular depres- every 8 hours. sion has been reported in premature and newborn infants. It has also been report- ed in infants born to mothers receiving chloramphenicol late in pregnancy.

120 Drugs

Gastrointestinal symptoms, peripheral Concomitant administration of phenobar- neuritis and optic neuritis are reported bital or rifampicin may decrease plasma rarely. concentrations of chloramphenicol.

Drug interactions Storage Chloramphenicol inhibits hepatic en- Preparations should be stored in tightly zymes. It thus prolongs the half-life of closed containers protected from light. drugs metabolized in the liver, including Following reconstitution, chlorampheni- phenytoin, oral anticoagulants and col injection is stable for 30 days. Cloudy steroids. solutions should be discarded.

Ciprofloxacin Tablet, 250mg (as hydrochloride)

• shigellosis, enteritis due to enterotoxi- General information genic Escherichia coli and infectious Ciprofloxacin is a synthetic fluoro- enteritis due to Salmonella enteritidis quinolone that acts as a specific inhibitor • enteritis due to Campylobacter jejuni in of bacterial DNA gyrase. It has a broad adults spectrum of efficacy against both • typhoid and paratyphoid fever Gram-negative and Gram-positive • uncomplicated anogenital infections, aerobic bacteria. Transfer of genes con- gonococcal conjunctivitis, chancroid taining DNA coding for antimicrobial and prostatitis in adults resistance has been reported but as yet is • osteomyelitis due to Salmonella spp. in of little clinical significance. adults • osteomyelitis due to Salmonella spp. Ciprofloxacin is rapidly absorbed from in children £ 5 years, together with the gastrointestinal tract. Peak plasma cloxacillin and either ceftriaxone or levels occur 0.5–1.5 hours after dosing. cefotaxime It is widely distributed in body tissues • moderate and severe pelvic inflamma- and concentrated in the bile. It has a tory disease in adults (hospitalized plasma half-life of 3–5 hours and is patients), together with metronida- excreted in the urine mainly as zole and doxycycline unchanged drug. • tularaemia and anthrax. Prophylaxis against meningitis due to Clinical information Neisseria meningitidis. Uses Dosage and administration Treatment of: Legionellosis in adults • legionellosis in adults 750mg orally every 12 hours for 10 days. • nosocomial pneumonia, together with Nosocomial pneumonia ceftazidime Adults: 500 mg i.v. every 12 hours, • cholera in patients who are severely together with ceftazidime 1 g i.v. every 8 dehydrated hours for 7 days.

121 WHO Model Prescribing Information — Drugs used in bacterial infections

Ciprofloxacin (continued) Chronic carriers should receive 500– 750mg orally every 12 hours for 4–6 Children: 10 mg/kg (maximum 300 mg) weeks (children: ampicillin 10mg/kg i.v. every 12 hours, together with cef- (maximum 250mg) i.m. every 6 hours tazidime 25 mg/kg (maximum 1 g) every for 4–6 weeks). 8 hours for 7 days. Prostatitis in adults In hospitals with a high prevalence of 500mg orally every 12 hours for 4–6 meticillin-resistant Staphylococcus aureus, weeks. vancomycin 1 g (children: 20 mg/kg; maximum 1 g) i.v. every 12 hours for Osteomyelitis due to Salmonella 10–14 days should be added to the above spp. in adults and children £ 5 years regimens. Adults: 750mg orally every 12 hours for 6 weeks. Cholera in patients who are severely dehydrated and shigellosis Children aged from 2 months up to 5 Adults: 1g orally in a single dose. years: 10–15mg/kg (maximum 500mg) orally every 12 hours to complete the Children: 20mg/kg (maximum 1g) treatment course of 6 weeks, following orally in a single dose. initial therapy with cloxacillin 25–50 mg/kg (maximum 2g) i.v. or i.m. every Patients with shigellosis due to Shigella 4–6 hours and ceftriaxone 50–75mg/kg dysenteriae serotype 1 should receive (maximum 1g) i.v. or i.m. every 24 hours 500mg (children: 10mg/kg; maximum for 4–6 days (or until clinical improve- 500mg) orally every 12 hours for 5 days. ment occurs). Enteritis due to Campylobacter Neonates: 10–15mg/kg (maximum jejuni in adults 500mg) orally every 12 hours to com- 500mg orally every 12 hours for 7–10 plete the treatment course of 6 weeks, days. following initial therapy with cloxacillin Enteritis due to enterotoxigenic 25–50mg/kg (maximum 2g) i.v. or i.m. Escherichia coli every 4–6 hours and cefotaxime 50– Adults: 500mg orally every 12 hours for 75mg/kg (maximum 2 g) i.v. every 8 3 days. hours for 4–6 days (or until clinical improvement occurs). Children: 10mg/kg (maximum 500mg) orally every 12 hours for 3 days. Uncomplicated anogenital gonococ- cal infections and gonococcal Ciprofloxacin is not licensed for use in conjunctivitis in adults children for this indication, but may be 500mg orally in a single dose. used for short courses if there are no suit- able alternatives. All patients with gonorrhoea should be treated concurrently for chlamydial Typhoid and paratyphoid fever and infection unless microbiological facilities infectious enteritis due to Salmo- exist to exclude the latter diagnosis. nella enteritidis Sexual partners should be treated Adults: 500–750mg orally every 12 hours simultaneously. for 5–14 days. Chancroid in adults Children: 10–15mg/kg (maximum 500mg orally in a single dose. (Longer 500mg) orally every 12 hours for 5–14 treatment courses may be necessary in days. immunocompromised patients.)

122 Drugs

Moderate or severe pelvic Use in pregnancy and early inflammatory disease in adults childhood Hospitalized patients Ciprofloxacin should not be used during 500mg orally every 12 hours plus pregnancy. Use in children is controver- metronidazole 400–500mg orally every 8 sial, since quinolones have been shown hours for at least 4 days (or for 48 hours to induce arthropathy in the weight- after clinical improvement occurs), fol- bearing joints of young animals. lowed by doxycycline 100mg orally Although damage to growing cartilage every 12 hours for 10–14 days. has not been demonstrated in humans, use of quinolones is not generally rec- Tularaemia ommended in children and adoles- Adults: 500 mg orally every 12 hours for cents. However, in severe infections the 10–14 days. benefits are considered to outweigh the Children: 10–15 mg/kg (maximum risk. 500 mg) orally every 12 hours for 10–14 days. Adverse effects Ciprofloxacin is generally well tolerated. Anthrax The most frequently reported adverse Adults: 750mg orally every 12 hours for effects are nausea, diarrhoea, vomiting, 7–10 days. dyspepsia, abdominal pain, headache, Children: 10–15mg/kg (maximum restlessness, tremor, confusion, rash, 750mg) orally every 12 hours for 7–10 dizziness and pruritus. days. Myalgia, tendinitis, and hepatic and renal disturbances have also been Prophylaxis against meningitis due reported. to Neisseria meningitidis Adults and children: 500mg orally in a Drug interactions single dose. Plasma levels of theophylline may be Contraindications increased. A prolonged bleeding time has been reported in patients receiving • Hypersensitivity to any quinolone. anticoagulants and ciprofloxacin concur- • Pregnancy. rently. Precautions The susceptibility of Shigella spp. to Reduced dosage should be considered ciprofloxacin has been reported to be in patients with hepatic or renal reduced in patients previously treated impairment. with nalidixic acid. Ciprofloxacin should be administered Overdosage cautiously to patients with epilepsy Gastric lavage is of value if performed since seizures may be precipitated. promptly. Electrolyte balance must be maintained. Serum concentrations of An adequate fluid intake must be ciprofloxacin may be lowered by ensured to prevent crystalluria. dialysis.

Storage Tablets should be stored in well-closed containers.

123 WHO Model Prescribing Information — Drugs used in bacterial infections

Clindamycin Injection, 150mg (as phosphate)/ml

• very severe pelvic inflammatory General information disease in adults (hospitalized patients), together with gentamicin Clindamycin is a semisynthetic deriva- and doxycycline tive of lincomycin belonging to the • septicaemia (initial empirical therapy) lincosamide group of antimicrobials. It in adults and children > 5 years, is active against most aerobic Gram- together with gentamicin. positive cocci, including staphylococci and Streptococcus pneumoniae, as well as Prophylaxis in contaminated surgery, several anaerobic Gram-negative and together with gentamicin. Gram-positive organisms. Dosage and administration Following intramuscular or intravenous Pneumonia due to Pneumocystis administration, clindamycin is rapidly carinii in adults hydrolysed and distributed into all 600mg i.v. or orally every 6 hours, tissues except the cerebrospinal fluid. together with primaquine 15mg orally The plasma half-life is 2–3 hours in every 6 hours for 21 days. adults and children with normal renal function but is prolonged in patients Aspiration pneumonia and lung with renal disease. The drug is excreted abscesses in the urine. Adults: 600mg i.v. every 8 hours for 14 days (once clinical improvement occurs, Clindamycin readily crosses the placenta 300–450mg orally every 6–8 hours and is excreted in breast milk. may be substituted). Children: 10mg/kg (maximum 450mg) Clinical information i.v. or i.m. every 6 hours for 14 days Uses (once clinical improvement occurs, 5– Treatment of: 10mg/kg (maximum 450mg) orally every 6–8 hours may be substituted). • pneumonia due to Pneumocystis carinii in adults, together with primaquine Pneumonia due to Staphylococcus • pneumonia due to Staphylococcus aureus in adults and children aureus in adults and children > 5 years > 5 years • aspiration pneumonia and lung ab- Adults: 600mg i.v. every 8 hours for scesses 10–14 days (once clinical improvement • streptococcal necrotizing fasciitis, occurs, 300–450mg orally every 6–8 together with benzylpenicillin hours may be substituted). • gangrene in patients allergic to peni- Children > 5 years: 10mg/kg (maxi- cillins, together with gentamicin and mum 450mg) i.v. or i.m. every 6 hours metronidazole for 10–14 days (once clinical improve- • pyomyositis ment occurs, 5–10mg/kg (maximum • osteomyelitis and septic arthritis due 450mg) orally every 6–8 hours may be to Staphylococcus aureus in adults and substituted). children > 5 years

124 Drugs

Streptococcal necrotizing fasciitis therapy is less than 4–6 weeks, treatment Adults: 600mg i.v. every 8 hours, should be completed with 300–450mg together with benzylpenicillin 4 million orally every 6 hours). IU i.v. or i.m. every 4 hours for at least 7 days. Children > 5 years: 10mg/kg (maximum 450mg) i.v. every 6 hours for 4–6 days (or Children: 10mg/kg (maximum 450mg) until clinical improvement occurs), fol- i.v. every 6 hours, together with ben- lowed by 10mg/kg (maximum 450mg) zylpenicillin 100000IU/kg (maximum 4 orally every 6 hours to complete the million IU) i.v. or i.m. every 4 hours for treatment course of 3–4 weeks. at least 7 days. Septic arthritis due to Staphylococ- Gangrene in patients allergic to cus aureus in adults and children penicillins > 5 years Adults: 600mg orally or i.v. every Adults: 600 mg i.v. every 8 hours for 2–3 6–8 hours, together with gentamicin weeks (if the duration of parenteral 5–7mg/kg i.v. or i.m. daily in divided therapy is less than 2–3 weeks, the treat- doses and metronidazole 500mg i.v. ment course should be completed with every 8 hours for at least 7 days (once 300–450 mg orally every 6 hours). clinical improvement occurs, rectal formulations of metronidazole may be Children > 5 years: 10 mg/kg (maximum substituted). 450 mg) i.v. every 6 hours for 4–6 days (or until clinical improvement occurs), fol- Children: 10mg/kg (maximum 450mg) lowed by 10 mg/kg (maximum 450 mg) orally or i.v. every 6–8 hours, together orally every 6 hours to complete the with gentamicin 7.5mg/kg i.v. or i.m. in treatment course of 2–3 weeks. 1–3 divided doses daily and metronida- zole 12.5mg/kg (maximum 500mg) i.v. In some cases, especially in adults, every 8 hours for at least 7 days (once repeated aspiration or surgical washout clinical improvement occurs, rectal for- of the joint may also be necessary. mulations of metronidazole may be Very severe pelvic inflammatory substituted). disease in adults Pyomyositis Hospitalized patients Adults: 600mg i.v. every 8 hours for 5–10 900mg i.v. every 8 hours, together with days (once clinical improvement occurs, either gentamicin 5–7mg/kg i.v. or i.m. 300–450mg orally every 4–6 hours may every 24 hours or gentamicin 1.5–2.0 be substituted). mg/kg i.v. or i.m. every 8 hours for at least 4 days (or for 48 hours after clinical Children: 10mg/kg (maximum 450mg) improvement occurs), followed by doxy- i.v. every 6 hours for 5–10 days cycline 100mg orally every 12 hours for (once clinical improvement occurs, 5– 10–14 days. 10mg/kg (maximum 450mg) orally every 4–6 hours may be substituted). Initial empirical therapy for septicae- mia in adults and children > 5 years Osteomyelitis due to Staphylococ- 600mg i.v. every 8 hours, together with cus aureus in adults and children either gentamicin 5–7mg/kg i.v. every 24 > 5 years hours or gentamicin 1.5mg/kg i.v. or i.m. Adults: 600mg i.v. every 8 hours for 4–6 every 8 hours. weeks (if the duration of parenteral

125 WHO Model Prescribing Information — Drugs used in bacterial infections

Clindamycin (continued) only when the need of the mother out- weighs the risk of harm to the fetus. Prophylaxis in contaminated surgery Adults and children: 600mg i.v., together Adverse effects with gentamicin 5mg/kg i.v. at induc- Nausea, vomiting, diarrhoea and tion of anaesthesia. abdominal pain are the most common adverse effects. Rarely, antimicrobial- Contraindications associated pseudomembranous colitis • Hypersensitivity to lincosamides. due to Clostridium difficile occurs. When • Severe hepatic or renal impairment. this is suspected, treatment should be • A history of ulcerative colitis or immediately discontinued. antimicrobial-associated colitis. Skin rashes and urticaria are frequent, while erythema multiforme and anaphy- Precautions laxis are rare. If clinically important or persistent diar- rhoea occurs, treatment should be imme- Drug interactions diately discontinued. Clindamycin may enhance the effect of Renal and hepatic function should be neuromuscular-blocking agents. monitored when treatment is prolonged. Storage Use in pregnancy Injections should be stored in tightly Safe use in pregnancy has not been closed containers. established. Clindamycin should be used

Cloxacillin1 Capsule, 500mg (as sodium salt) Powder for oral solution, 125mg (as sodium salt)/5ml Powder for injection, 500mg (as sodium salt) in vial

absorption. It is well distributed in the General information tissues, has a plasma half-life of about 30 Cloxacillin is a semisynthetic derivative minutes and is rapidly excreted in the of penicillin that is resistant to break- urine mainly unchanged, but also as down by the enzyme penicillinase. It metabolites. It crosses the placenta and is has a broad spectrum of activity and excreted in breast milk. is bactericidal against most strains of b-lactamase-producing Staphylococcus aureus. Clinical information Uses Cloxacillin is absorbed from the gas- Treatment of: trointestinal tract but food decreases its • pneumonia due to Staphylococcus aureus in adults and children > 5 years 1 Dicloxacillin, flucloxacillin, nafcillin or oxa- cillin may serve as alternatives.

126 Drugs

• pneumonia due to Staphylococcus Children > 5 years: 50mg/kg (maximum aureus in children aged from 2 months 2g) i.v. or i.m. every 6 hours for 10–14 to 5 years and nosocomial pneumonia, days. together with gentamicin • localized purulent skin lesions, im- Children aged from 2 months to 5 years: petigo and pyomyositis 25–50mg/kg (maximum 2g) orally • contaminated soft tissue injuries, every 6 hours, together with gentamicin together with gentamicin and metro- 7.5mg/kg i.v. in 1–3 divided doses daily nidazole for at least 3 weeks. • septic arthritis (initial empirical Nosocomial pneumonia therapy) in adults, together with cef- Adults: 1–2g i.v. every 6 hours, together triaxone with gentamicin 5–7mg/kg i.v. daily in • septic arthritis and osteomyelitis due divided doses for 7 days. to Staphylococcus aureus in adults • septic arthritis (initial empirical Children: 50mg/kg (maximum 2g) i.v. therapy), septic arthritis and every 6 hours, together with gentamicin osteomyelitis due to Staphylococcus 7.5mg/kg in 1–3 divided doses daily for aureus, and septicaemia (initial em- 7 days. pirical therapy) in children, together In hospitals with a high prevalence of with ceftriaxone or cefotaxime meticillin-resistant Staphylococcus aureus, • osteomyelitis due to Haemophilus vancomycin 1 g (children: 20 mg/kg; influenzae or unknown pathogen in maximum 1 g) i.v. every 12 hours for children £ 5 years, together with 10–14 days should also be added to the amoxicillin + clavulanic acid and above regimens. either ceftriaxone or cefotaxime • osteomyelitis due to Salmonella spp. in Localized purulent skin lesions and children £ 5 years, together with either impetigo ceftriaxone or cefotaxime and either Adults: 250–500mg orally every 6 hours sulfamethoxazole + trimethoprim or for 5–7 days. amoxicillin or ciprofloxacin • infective endocarditis (initial empiri- Children: 12.5–25mg/kg (maximum cal therapy), together with benzyl- 500mg) orally every 6 hours for 5–7 penicillin and gentamicin days. • endocarditis due to meticillin- Pyomyositis susceptible Staphylococcus aureus, Adults: 2g i.v. or i.m. every 6 hours for together with gentamicin 5–10 days (once clinical improvement • septicaemia (initial empirical therapy) occurs, 500mg orally every 6 hours may in adults, together with gentamicin. be substituted). Dosage and administration Children: 25–50mg/kg (maximum 2g) Intravenous formulations of cloxacillin i.v. or i.m. every 6 hours for 5–10 days should be administered over 2 minutes. (once clinical improvement occurs, 12.5– 25mg/kg (maximum 500mg) orally Pneumonia due to Staphylococcus every 6 hours may be substituted). aureus Adults: 1–2g i.v. or i.m. every 6 hours for Contaminated soft tissue injuries 10–14 days. Adults: 2g i.v. or i.m. every 6 hours for 5–10 days (once clinical improvement occurs, 500mg orally every 6 hours may

127 WHO Model Prescribing Information — Drugs used in bacterial infections

Cloxacillin (continued) or i.m. every 24 hours for 4–6 days (or until clinical improvement occurs), be substituted), supplemented by gen- followed by 12.5mg/kg (maximum tamicin 5–7mg/kg i.v. or i.m. daily in 500mg) orally every 6 hours to complete divided doses and metronidazole 500mg the treatment course of 3–4 weeks. i.v. every 8 hours (once clinical improve- ment occurs, oral or rectal formulations Neonates: 25–50mg/kg (maximum 2g) of metronidazole may be substituted). i.v. or i.m. every 4–6 hours, together with cefotaxime 50–75mg/kg (maximum 2g) Children: 25–50mg/kg (maximum 2g) i.v. every 8 hours for 4–6 days (or until i.v. or i.m. every 6 hours for 5–10 days clinical improvement occurs), followed (once clinical improvement occurs, by 12.5mg/kg (maximum 500mg) orally 12.5–25mg/kg (maximum 500mg) every 6 hours to complete the treatment orally every 6 hours may be substituted), course of 3–4 weeks. supplemented by gentamicin 7.5mg/kg i.v. or i.m. in 1–3 divided doses daily and Osteomyelitis due to Haemophilus metronidazole 12.5mg/kg (maximum influenzae or unknown pathogen in 500mg) i.v. every 8 hours (once clinical children £ 5 years improvement occurs, oral or rectal Children aged from 2 months to 5 years: formulations of metronidazole may be 25–50mg/kg (maximum 2g) i.v. or i.m. substituted). every 4–6 hours, together with ceftriax- one 50–75mg/kg (maximum 1g) i.v. or Osteomyelitis due to Staphylococcus i.m. every 24 hours for 4–6 days (or until aureus clinical improvement occurs), followed Adults: 2g i.v. or i.m. every 6 hours for by amoxicillin 15mg/kg + clavulanic at least the initial 14 days of therapy, but acid (maximum 500 mg) orally every 8 preferably the entire treatment course of hours to complete the treatment course 4–6 weeks (if the duration of parenteral of 3–4 weeks. therapy is less than 4–6 weeks, the treat- ment course should be completed with Neonates: 25–50mg/kg (maximum 2g) 1g orally every 6 hours). i.v. or i.m. every 4–6 hours, together with cefotaxime 50–75mg/kg (maximum 2g) Children > 5 years: 25–50mg/kg (maxi- i.v. every 8 hours for 4–6 days (or until mum 2g) i.v. or i.m. every 4–6 hours for clinical improvement occurs), followed 4–6 days (or until clinical improvement by amoxicillin 15mg/kg + clavulanic occurs), followed by 25mg/kg (maxi- acid (maximum 500 mg) orally every 8 mum 500mg) orally every 6 hours to hours to complete the treatment course complete the treatment course of 3–4 of 3–4 weeks. weeks or 25mg/kg (maximum 500mg) orally every 6 hours to complete the Osteomyelitis due to Salmonella treatment course of 3–4 weeks, following spp. in children £ 5 years initial therapy with ceftriaxone 50–75 Children aged from 2 months to 5 years: mg/kg (maximum 1g) i.v. or i.m. every 25–50mg/kg (maximum 2g) i.v. or i.m. 24 hours for 4–6 days (or until clinical every 4–6 hours, together with ceftriax- improvement occurs). one 50–75mg/kg (maximum 1g) i.v. or i.m. every 24 hours for 4–6 days (or until Children aged from 2 months to 5 years: clinical improvement occurs), followed 25–50mg/kg (maximum 2g) i.v. or i.m. by either sulfamethoxazole 20mg/kg + every 4–6 hours, together with ceftria- trimethoprim 4mg/kg (maximum 800 xone 50–75mg/kg (maximum 1g) i.v. mg + 160mg) orally every 12 hours or

128 Drugs amoxicillin 7.5–15mg/kg (maximum 1 orally every 6 hours to complete the g) orally every 8 hours or ciprofloxacin treatment course of 2–3 weeks, following 10–15mg/kg (maximum 500mg) orally initial therapy with ceftriaxone 50–75 every 12 hours to complete the treatment mg/kg (maximum 1 g) i.v. or i.m. every course of 6 weeks. 24 hours for 4–6 days (or until clinical improvement occurs). Neonates: 25–50mg/kg (maximum 2g) i.v. or i.m. every 4–6 hours, together with Children aged from 2 months to 5 years: cefotaxime 50–75mg/kg (maximum 2g) 25–50 mg/kg (maximum 2 g) i.v. or i.m. i.v. every 8 hours for 4–6 days (or until every 4–6 hours, together with ceftriax- clinical improvement occurs), followed one 50–75 mg/kg (maximum 1 g) i.v. or by either sulfamethoxazole 20mg/kg i.m. every 24 hours for 4–6 days (or until + trimethoprim 4mg/kg (maximum clinical improvement occurs), followed 800mg + 160mg) orally every 12 hours or by 12.5 mg/kg (maximum 500 mg) orally amoxicillin 7.5–15mg/kg (maximum 1 every 6 hours to complete the treatment g) orally every 8 hours or ciprofloxacin course of 2–3 weeks. 10–15mg/kg (maximum 500mg) orally every 12 hours to complete the treatment Neonates: 25–50 mg/kg (maximum 2 g) course of 6 weeks. i.v. or i.m. every 4–6 hours, together with cefotaxime 50–75 mg/kg (maximum 2 g) Initial empirical therapy for septic i.v. or i.m. every 8 hours for 4–6 days (or arthritis until clinical improvement occurs), fol- Adults: 2g i.v. or i.m. every 6 hours, lowed by 12.5 mg/kg (maximum 500 together with ceftriaxone 1–2g i.v. or i.m. mg) orally every 6 hours to complete the every 24 hours. treatment course of 2–3 weeks. Children ≥ 2 months: 25–50mg/kg In some cases, repeated aspiration or (maximum 2g) i.v. or i.m. every 6 hours, surgical washout of the joint may also be together with ceftriaxone 25–50mg/kg necessary. (maximum 2g) i.v. or i.m. every 24 hours. Initial empirical therapy for infective Neonates: 25–50mg/kg (maximum 2g) endocarditis i.v. or i.m. every 6 hours, together with Adults: 2g i.v. every 4 hours, together cefotaxime 50–75mg/kg (maximum 2g) with benzylpenicillin 3 million IU i.v. i.v. every 8 hours. every 4 hours and gentamicin 2mg/kg i.v. every 8 hours. Septic arthritis due to Staphylo- coccus aureus Children: 50mg/kg (maximum 2g) i.v. Adults: 2 g i.v. or i.m. every 6 hours for every 4 hours, together with benzylpeni- 2–3 weeks (if the duration of parenteral cillin 50000IU/kg (maximum 3 million therapy is less than 2–3 weeks, the treat- IU) i.v. every 4 hours and gentamicin ment course should be completed with 2.5mg/kg (maximum 80mg) i.v. every 8 1 g orally every 6 hours). hours. Children > 5 years: 25–50 mg/kg (maxi- Endocarditis due to Staphylococcus mum 2 g) i.v. or i.m. every 4–6 hours for aureus (strains susceptible to 4–6 days (or until clinical improvement meticillin) occurs), followed by 25 mg/kg (maxi- Adults: 2g i.v. every 4 hours for 6 weeks, mum 500 mg) orally every 6 hours to supplemented for the first 7 days by complete the treatment course of 2–3 gentamicin 1mg/kg i.v. every 8 hours. weeks or 25 mg/kg (maximum 500 mg)

129 WHO Model Prescribing Information — Drugs used in bacterial infections

Cloxacillin (continued) Rapid intravenous administration of large doses of cloxacillin may cause Children: 50mg/kg (maximum 2g) i.v. hyperkalaemia, dysrhythmias and car- every 4 hours for 6 weeks, supplemented diac arrest, particularly in patients with for the first 7 days by gentamicin impaired renal function. 1mg/kg i.v. every 8 hours. Use in pregnancy Initial empirical therapy for There is no evidence that cloxacillin septicaemia is teratogenic. It may be used during Adults and children > 5 years: 2g i.v. pregnancy. every 4–6 hours, together with either gen- tamicin 5–7mg/kg i.v. every 24 hours or Adverse effects gentamicin 1.5mg/kg i.v. or i.m. every 8 Hypersensitivity reactions are the most hours. common adverse effects, ranging in Children aged from 2 months to 5 years: severity from skin rashes to immediate 50mg/kg (maximum 2g) i.v. every anaphylaxis. 4–6 hours, together with ceftriaxone Phlebitis or thrombophlebitis sometimes 50mg/kg (maximum 2g) i.v. or i.m. follows intravenous administration. every 24 hours. Nausea, vomiting, flatulence, diarrhoea Neonates: 50 mg/kg (maximum 2 g) i.v. and epigastric pain can occur and may every 4–6 hours, together with cefo- be severe enough to warrant discontinu- taxime 50–75 mg/kg (maximum 2 g) i.v. ation of the drug. every 8 hours. Interstitial nephritis has been reported. Contraindications Neutropenia and thrombocytopenia are Known hypersensitivity to penicillins or rare. cefalosporins. Overdosage Precautions Overdosage can cause convulsions, Facilities should be available for treating paralysis and even death. anaphylaxis whenever penicillins are Excessive blood concentrations can be used. Patients should be questioned lowered by haemodialysis. carefully about previous allergic reac- tions before the first dose is adminis- Storage tered. If a skin rash develops, the patient Preparations of cloxacillin should be should be transferred to a different class stored in tightly closed containers. of antimicrobial. Solutions are stable for 3 days after reconstitution.

130 Drugs

Doxycycline Capsule or tablet, 100mg (as hyclate) Powder for injection, 100mg (as hyclate) in ampoule

• syphilis in patients allergic to peni- General information cillins Doxycycline is a broad-spectrum anti- • Lyme disease (early stage), anthrax, biotic derived from and closely related plague, relapsing fever, leptospirosis to oxytetracycline. It differs from the and rickettsial infections in adults and > tetracyclines in being more extensively children 8 years > absorbed and more lipid-soluble, and • brucellosis in adults and children 8 possesses a longer serum half-life that is years, together with rifampicin or independent of the patient’s renal status. rifampicin plus either streptomycin or gentamicin. Clinical information Dosage and administration Acute bronchitis in adults and Uses children > 8 years Treatment of: Adults: 100mg orally every 12 hours for • pneumonia and acute bronchitis in 5 days. adults and children > 8 years Children > 8 years: 2mg/kg (maximum • ornithosis and Q fever in adults and 100mg) orally every 12 hours for 5 days. children > 8 years • melioidosis in adults and children > 8 Pneumonia in adults and children years, together with ceftazidime > 8 years • cholera in patients who are severely Ambulatory patients dehydrated Adults: 100mg orally every 12 hours for • prostatitis due to Chlamydia trachoma- 7–10 days. tis or Ureaplasma urealyticum in adults • human and animal bites and Children > 8 years: 2 mg/kg (maximum clenched-fist injuries in patients al- 100 mg) orally every 12 hours for 7–10 lergic to penicillins, together with days. metronidazole Ornithosis, Q fever and anthrax in • granuloma inguinale in adults adults and children > 8 years • lymphogranuloma venereum and Adults: 100mg orally every 12 hours for other chlamydial infections in adults 7–10 days. and children > 8 years • pelvic inflammatory disease in adults Children > 8 years: 2mg/kg (maximum (ambulatory patients), together with 100mg) orally every 12 hours for 7–10 metronidazole and ceftriaxone days. • very severe pelvic inflammatory disease in adults (hospitalized Melioidosis in adults and children patients), together with gentamicin > 8 years and clindamycin Adults: 100mg orally or i.v. every 12 • moderate or severe pelvic inflam- hours, together with ceftazidime 2g i.v. matory disease in adults (hospitalized every 8 hours for at least 14 days. patients), together with ceftriaxone or ciprofloxacin plus metronidazole

131 WHO Model Prescribing Information — Drugs used in bacterial infections

Doxycycline (continued) Other chlamydial infections and plague in adults and children Children > 8 years: 2mg/kg (maximum > 8 years 100mg) orally or i.v. every 12 hours, Adults: 100mg orally every 12 hours for together with ceftazidime 50mg/kg 7 days. (maximum 2g) i.v. every 8 hours for at least 14 days. Children > 8 years: 2mg/kg (maximum 100mg) orally every 12 hours for 7 days. After the initial intensive therapy, eradi- cation of any secondary infection is Pelvic inflammatory disease in recommended with oral doxycycline for adults at least 3 months. Ambulatory patients 100mg orally every 12 hours, together Cholera in patients who are severely with metronidazole 400–500mg orally dehydrated every 8 hours for 10 days, following Adults: 300mg orally in a single dose. initial therapy with ceftriaxone 250mg i.m. in a single dose. Children > 8 years: 2mg/kg (maximum 100mg) orally in a single dose. Hospitalized patients with very severe disease Prostatitis due to Chlamydia tracho- 100mg orally every 12 hours for 10–14 matis or Ureaplasma urealyticum in days, following initial therapy with either adults gentamicin 5–7mg/kg i.v. or i.m. every 100mg orally every 12 hours for 14 days. 24 hours or gentamicin 1.5–2.0mg/kg i.v. Human and animal bites and or i.m. every 8 hours, together with clin- clenched-fist injuries in patients damycin 900mg i.v. every 8 hours for at allergic to penicillins least 4 days (or for 48 hours after clinical Adults: 100mg orally every 24 hours for improvement occurs). 5–10 days, supplemented by metronida- Hospitalized patients with moderate or zole 400–500mg orally every 12 hours. severe disease Children > 8 years: 2mg/kg (maximum 100mg orally every 12 hours for 10–14 100mg) orally every 24 hours for 5–10 days, following initial therapy with either days, supplemented by metronidazole ceftriaxone 250mg i.m. every 12 hours 10–12.5mg/kg (maximum 250mg) orally for at least 4 days (or for 48 hours after every 12 hours. clinical improvement occurs) or cipro- floxacin 500mg orally every 12 hours Lymphogranuloma venereum in plus metronidazole 400–500mg orally adults and children > 8 years every 8 hours for at least 4 days (or for Adults: 100mg orally every 12 hours for 48 hours after clinical improvement 14 days. occurs). Children > 8 years: 2mg/kg (maximum Syphilis in patients allergic to 100mg) orally every 12 hours for 14 penicillins days. Adults: 100mg orally every 12 hours for Granuloma inguinale in adults 30 days. 100 mg orally every 12 hours for 14 days Children > 8 years: 2 mg/kg (maximum (or until the lesion has completely 100 mg) orally every 12 hours for 30 healed). days.

132 Drugs

Lyme disease (early stage) in adults Children > 8 years: 2mg/kg (maximum and children > 8 years 100mg) orally every 12 hours for 7–10 Adults: 100mg orally every 12 hours for days (or for 48 hours after resolution of 10–21 days. fever).

Children > 8 years: 2mg/kg (maximum Contraindications 100mg) orally every 12 hours for 10–21 days. • Known hypersensitivity. • Pregnancy. Relapsing fever in adults and • Age up to 8 years. children > 8 years Adults: 100mg orally in a single dose. Precautions Children > 8 years: 2mg/kg (maximum Troublesome oesophagitis may be 100mg) orally in a single dose. averted if the patient is propped up while swallowing capsules or tablets Leptospirosis in adults and children and washes them down immediately > 8 years with a glass of water. Capsules and Adults: 100mg orally every 12 hours for tablets should not be taken with milk or 5–7 days. with magnesium or aluminium salts since these impair the absorption of > Children 8 years: 2mg/kg (maximum doxycycline. 100mg) orally every 12 hours for 5–7 days. Use in pregnancy and early Brucellosis in adults and children childhood > 8 years Doxycycline is generally contraindicated Adults: 100 mg orally every 12 hours, in pregnancy and during early child- together with rifampicin 600 mg orally hood. However, it can be given to chil- every 24 hours for 6 weeks or 100 mg dren aged up to 8 years in a single dose orally every 12 hours for 6 weeks, sup- for the treatment of cholera and relaps- plemented for the first 2 weeks by either ing fever. Because it is deposited in streptomycin 1 g i.m. every 24 hours or developing teeth and bones and impairs gentamicin 5–7 mg/kg i.v. every 24 skeletal calcification, it can result in hours. abnormal osteogenesis and permanent staining of teeth, and occasionally causes Children > 8 years: 2 mg/kg (maximum hypoplasia of dental enamel. 100 mg) orally every 12 hours, together with rifampicin 15 mg/kg (maximum Adverse effects 600 mg) orally every 24 hours for 6 Gastrointestinal irritation is common and weeks or 2 mg/kg (maximum 100 mg) phototoxic reactions and increased vul- orally every 12 hours for 6 weeks, sup- nerability to sunburn have been reported. plemented for the first 2 weeks by either streptomycin 15 mg/kg (maximum 1 g) Transient depression of bone growth i.m. every 24 hours or gentamicin 7.5 is largely reversible, but discoloration mg/kg i.v. in 1–3 divided doses daily. of teeth and enamel hypoplasia are permanent. Rickettsial infections in adults and children > 8 years Drug interactions Adults: 100mg orally every 12 hours for The action of oral anticoagulants may be 7–10 days (or for 48 hours after resolu- potentiated. Severe renal failure has been tion of fever).

133 WHO Model Prescribing Information — Drugs used in bacterial infections

Doxycycline (continued) Storage Doxycycline capsules, tablets and reported in patients who have received powder for injection should be kept in a halogenated anaesthetic agent while well-closed containers, protected from taking doxycycline. light.

Erythromycin Capsule or tablet, 250mg (as stearate or ethyl succinate) Powder for oral suspension, 125mg (as stearate or ethyl succinate) Eye ointment, 1%

• ornithosis and Q fever in children £ 8 General information years Erythromycin is a macrolide antibiotic • gingival infections and periodontitis produced by Streptomyces erythreus. • enteritis due to Campylobacter jejuni It has selective bacteriostatic activity • prostatitis due to Chlamydia tracho- against both streptococci and staphylo- matis or Ureaplasma urealyticum and cocci and some Gram-positive bacilli. chancroid in adults • lymphogranuloma venereum, chla- Because erythromycin is inactivated by mydial ophthalmia, other chlamydial gastric juices, oral formulations are pro- infections, and syphilis in patients tected by an enteric coating. The drug allergic to penicillins diffuses rapidly into all tissues except • relapsing fever. the brain and cerebrospinal fluid, and Prevention of neonatal gonococcal con- readily crosses the placental barrier. The junctivitis and recurrence of rheumatic plasma half-life is approximately 90 fever due to group A b-haemolytic strep- minutes. Erythromycin is partially tococci in patients allergic to penicillins. demethylated in the liver and excreted largely via the bile and faeces. Postsplenectomy prophylaxis. Dosage and administration Erythromycin tablets should not be Clinical information broken in half before administration. Uses Treatment of: Acute pharyngitis and acute cervical adenitis in patients allergic to • acute pharyngitis and acute cervical ade- penicillins nitis in patients allergic to penicillins Adults: 500mg orally every 6 hours for • diphtheria and legionellosis 10 days. • pneumonia in adults and children > 5 years Children: 10–15mg/kg (maximum • atypical pneumonia in adults and chil- 500mg) orally every 6 hours for 10 days. dren > 5 years, together with either Diphtheria chloramphenicol or cefuroxime or ceftriaxone or benzylpenicillin or Adults: 500mg orally every 6 hours for benzylpenicillin plus gentamicin 7 days, following initial therapy with • pertussis (whooping cough) in chil- diphtheria antitoxin 20000–100000IU i.v. dren or i.m.

134 Drugs

Children: 10–15mg/kg (maximum Legionellosis 500mg) orally every 6 hours for 7 days, Adults: 1g i.v. every 6 hours for 10 days following initial therapy with diphtheria (once clinical improvement occurs, antitoxin 20000–100000IU i.v. or i.m. 500mg orally every 6 hours may be substituted). Vaccination with diphtheria–pertussis– tetanus should be offered during conva- Children: 10mg/kg (maximum 500mg) lescence. i.v. every 6 hours for 10 days (once clinical improvement occurs, 7.5mg/kg Pneumonia in adults and children (maximum 500mg) orally every 6 hours > 5 years may be substituted). Ambulatory patients Adults: 500mg orally every 6 hours for Pertussis (whooping cough) in 5 days. children 50mg/kg (maximum 2g) orally in 4 Children > 5 years: 10–15mg/kg (maxi- divided doses daily for 14 days. mum 500mg) orally every 6 hours for 5 days. Ornithosis and Q fever in children £ 8 years Patients with atypical pneumonia 10–15mg/kg (maximum 500mg) orally should receive treatment for 14 days. every 6 hours for 7–10 days. Hospitalized patients with atypical Gingival infections and periodontitis pneumonia Adults: 250mg orally every 6 hours for 5 Adults: 1g i.v. every 6 hours for 14 days, days. supplemented for the first 5 days by benzylpenicillin 2 million IU i.v. or i.m. Children: 7.5mg/kg (maximum 250mg) every 4–6 hours or for the first 7 days by orally every 6 hours for 5 days. either chloramphenicol 1g i.v. every 6 hours or cefuroxime 1.0–1.5g i.v. every Enteritis due to Campylobacter 6–8 hours or ceftriaxone 1g i.v. or i.m. jejuni every 12–24 hours or benzylpenicillin 2 Adults: 500mg orally every 6 hours for million IU i.v. or i.m. every 4–6 hours 7–10 days. plus gentamicin 5–7mg/kg i.v. daily in Children: 10mg/kg (maximum 500mg) divided doses. orally every 6 hours for 7–10 days. Children: 10mg/kg (maximum 1g) i.v. Prostatitis due to Chlamydia tracho- every 6 hours for 14 days, supplemen- matis or Ureaplasma urealyticum in ted for the first 5 days by benzylpeni- adults cillin 50000–100000IU/kg (maximum 2 500mg orally every 6 hours for 14 days. million IU) i.v. or i.m. every 4–6 hours or for the first 7 days by either chloram- Lymphogranuloma venereum phenicol 25mg/kg (maximum 750mg) Adults: 500mg orally every 6 hours for i.v. every 6 hours or cefuroxime 50–60 14 days. mg/kg (maximum 1.5g) i.v. every 6–8 hours or ceftriaxone 50mg/kg (maxi- Children: 12.5mg/kg (maximum 500mg) mum 1g) i.v. or i.m. every 12–24 hours orally every 6 hours for 14 days. or benzylpenicillin 50000–100000IU/kg Chlamydial ophthalmia (maximum 2 million IU) i.v. or i.m. every 12.5mg/kg (as syrup; maximum 500mg) 4–6 hours plus gentamicin 7.5mg/kg i.v. orally every 6 hours for 14 days. in 1–3 divided doses daily.

135 WHO Model Prescribing Information — Drugs used in bacterial infections

Erythromycin (continued) Precautions Hepatic function should be monitored in Other chlamydial infections patients with a previous history of liver Adults: 500mg orally every 6 hours for disease. 7 days. Children: 10–15mg/kg (maximum Use in pregnancy 500mg) orally every 6 hours for 7 days. Erythromycin has not been shown to be mutagenic, teratogenic or embryotoxic; Syphilis in patients allergic to it can be used during pregnancy. penicillins Adults: 500mg orally every 6 hours for Adverse effects 15 days. Nausea, vomiting and diarrhoea can occur. Children: 7.5–12.5mg/kg (maximum 250mg) orally every 6 hours for 30 Cholestatic hepatitis, which may present days. with symptoms suggestive of acute cholecystitis, occasionally complicates Chancroid in adults prolonged courses of treatment. Symp- 500mg orally every 6 hours for 7 days. toms resolve rapidly when the drug is (Longer treatment courses may be neces- withdrawn. sary in immunocompromised patients.) Anaphylaxis and other hypersensitivity Relapsing fever reactions are rare. Adults: 500mg orally in a single dose. Children: 12.5mg/kg (maximum Drug interactions 500mg) orally in a single dose. Erythromycin, chloramphenicol and clindamycin have a similar bacteriostatic Prevention of neonatal gonococcal action and tend to be mutually antago- conjunctivitis nistic when administered together. A single application of eye ointment Erythromycin decreases the rate of immediately after birth should be metabolism of carbamazepine and war- sufficient. farin in the liver to a degree that can warrant readjustment of dosage. Prevention of recurrence of rheumat- ic fever due to group A b-haemolytic Overdosage streptococci in patients allergic to Symptoms of overdosage include severe penicillins nausea, vomiting, diarrhoea and hearing Adults and children: 250mg orally every loss. Induction of emesis or gastric 12 hours. lavage may be of value if undertaken Postsplenectomy prophylaxis within a few hours of ingestion. Adults: 250mg orally every 24 hours. Storage Children: 7.5mg/kg (maximum 250mg) Capsules and tablets should be stored in orally every 24 hours. tightly closed containers. Suspension and eye ointment should be stored in Contraindications well-closed containers protected from Known hypersensitivity to erythromycin light. or other macrolides.

136 Drugs

Gentamicin Injection, 10mg, 40mg (as sulfate)/ml in 2-ml vial

zole and either benzylpenicillin or General information clindamycin Gentamicin is a broad-spectrum amino- • contaminated soft tissue injuries, glycoside produced by Micromonospora together with metronidazole and purpurea. It is bactericidal against many cloxacillin aerobic Gram-negative bacteria but has • very severe pelvic inflammatory dis- little activity against most Gram-positive ease in adults (hospitalized patients), organisms with the exception of together with clindamycin and doxy- staphylococci. cycline • infective endocarditis (initial empiri- Gentamicin is poorly absorbed from the cal therapy), together with benzyl- gastrointestinal tract. After parenteral penicillin and cloxacillin administration, it is widely distributed • infective endocarditis (initial empiri- in the body tissues and fluids. Its pene- cal therapy) in patients allergic to tration into the cerebrospinal fluid is penicillins or with nosocomial infec- poor. Its plasma half-life is 2–4 hours and tions, and prosthetic valve endocardi- it is excreted unchanged in the urine. A tis, together with vancomycin small fraction is tightly bound intracel- • endocarditis due to a-haemolytic lularly and accumulates in the body streptococci, together with benzyl- tissues. It readily crosses the placenta penicillin or ampicillin and is distributed in breast milk. • endocarditis due to enterococci, together with benzylpenicillin or ampicillin Clinical information • endocarditis due to meticillin- Uses susceptible Staphylococcus aureus, to- gether with cloxacillin Treatment of: • culture-negative endocarditis, to- • pneumonia in adults and children > 5 gether with benzylpenicillin years, together with benzylpenicillin • neonatal meningitis due to unknown • atypical pneumonia in adults and chil- pathogen and neonatal meningitis dren > 5 years, together with benzyl- due to Listeria monocytogenes, together penicillin and erythromycin with ampicillin • nosocomial pneumonia, together with • neonatal meningitis due to group B cloxacillin or ceftazidime streptococci, together with benzyl- • pneumonia due to Staphylococcus penicillin aureus in children aged from 2 months • brucellosis, together with doxycycline to 5 years, together with cloxacillin or sulfamethoxazole + trimethoprim • neonatal pneumonia, together with • tularaemia and plague amoxicillin • septicaemia (initial empirical therapy) • acute cholecystitis and acute pyelo- in adults and children > 5 years, nephritis, together with ampicillin together with cloxacillin or cefazolin • acute peritonitis, together with ampi- or clindamycin or chloramphenicol cillin and metronidazole • neonatal septicaemia (initial empirical • gangrene, together with metronida- therapy), together with ampicillin.

137 WHO Model Prescribing Information — Drugs used in bacterial infections

Gentamicin (continued) Neonatal pneumonia 2.5mg/kg i.v. every 8 hours (neonates Prophylaxis in contaminated surgery, <7 days: 2.5mg/kg i.v. every 12 hours), together with clindamycin. together with amoxicillin 30mg/kg i.v. every 12 hours for a total of at least 5 days. Dosage and administration The dosages should be reduced in Nosocomial pneumonia patients with renal impairment. Adults: 5–7mg/kg i.v. daily in divided doses for 7 days, supplemented by either When gentamicin is used in combination cloxacillin 1–2g i.v. every 6 hours or cef- with a b-lactam antimicrobial in the treat- tazidime 1g i.v. every 8 hours. ment of endocarditis, it should be admin- istered every 8 hours. Basal plasma levels Children: 7.5mg/kg i.v. in 1–3 divided of gentamicin should not exceed 1 mg/l. doses daily for 7 days, supplemented by The maximum period of gentamicin either cloxacillin 50mg/kg (maximum therapy without monitoring plasma 2g) i.v. every 6 hours or ceftazidime 25 levels should be 72 hours. If vancomycin mg/kg (maximum 1g) i.v. every 8 hours. is used, peak plasma levels of 30–40 mg/l In hospitals with a high prevalence of and basal plasma levels of 5–15 mg/l are meticillin-resistant Staphylococcus aureus, recommended. These levels are specific vancomycin 1 g (children: 20 mg/kg; for the management of endocarditis and maximum 1 g) i.v. every 12 hours for do not apply to other circumstances. 10–14 days should be added to the above Pneumonia in adults and children regimens. >5 years Acute cholecystitis Hospitalized patients Adults: 5–7mg/kg i.v. daily in divided Adults: 5–7mg/kg i.v. daily in divided doses, together with ampicillin 1–2g i.v. doses, together with benzylpenicillin 2 or i.m. every 6 hours for up to 7 days. million IU i.v. or i.m. every 4–6 hours for 7 days. Children: 7.5mg/kg i.v. in 1–3 divided doses daily, together with ampicillin Children >5 years: 7.5mg/kg i.v. in 1–3 25–50mg/kg (maximum 2g) i.v. or i.m. divided doses daily, together with ben- every 6 hours for up to 7 days. zylpenicillin 50000–100000IU/kg (maxi- mum 2 million IU) i.v. or i.m. every 4–6 Acute peritonitis hours for 7 days. Adults: 5–7mg/kg i.v. daily in divided doses for at least 7 days, supplemented Patients with atypical pneumonia by ampicillin 2g i.v. or i.m. every 6 hours should also receive erythromycin 1g and metronidazole 500mg i.v. every 8–12 (children: 10mg/kg; maximum 1g) i.v. hours. every 6 hours for 14 days. Children: 7.5mg/kg i.v. in 1–3 divided Pneumonia due to Staphylococcus doses daily for at least 7 days, aureus in children aged from 2 supplemented by ampicillin 50mg/kg months to 5 years (maximum 2g) i.v. or i.m. every 6 7.5mg/kg i.v. in 1–3 divided doses daily, hours and metronidazole 12.5mg/kg together with cloxacillin 25–50mg/kg (maximum 500mg) i.v. every 8–12 hours. (maximum 2g) orally every 6 hours for at least 3 weeks. For patients who are allergic to peni- cillins, ampicillin should be deleted from the above regimens.

138 Drugs

Acute pyelonephritis (maximum 500mg) i.v. every 8 hours Adults: 5–7mg/kg orally daily in (once clinical improvement occurs, oral divided doses for 7 days, supplemented or rectal formulations of metronidazole for up to 14 days by ampicillin 1–2g i.v. may be substituted) and cloxacillin 25– or i.m. every 6 hours. 50mg/kg (maximum 2g) i.v. or i.m. every 6 hours (once clinical improve- Children: 7.5mg/kg orally in 1–3 ment occurs, cloxacillin 12.5–25mg/kg divided doses daily for 7 days, supple- (maximum 500mg) orally every 6 hours mented for up to 14 days by ampicillin may be substituted). 50mg/kg (maximum 2g) i.v. or i.m. every 6 hours. Very severe pelvic inflammatory disease in adults Gangrene Hospitalized patients Adults: 5–7mg/kg i.v. or i.m. daily in 5–7mg/kg i.v. or i.m. every 24 hours or divided doses for at least 7 days, sup- 1.5–2.0mg/kg i.v. or i.m. every 8 hours, plemented by benzylpenicillin 4 million together with clindamycin 900mg i.v. IU i.v. or i.m. every 4 hours and metroni- every 8 hours for at least 4 days (or for 48 dazole 500mg i.v. every 8 hours (once hours after clinical improvement occurs), clinical improvement occurs, rectal for- followed by doxycycline 100mg orally mulations of metronidazole may be every 12 hours for 10–14 days. substituted). Initial empirical therapy for infective Children: 7.5mg/kg i.v. or i.m. in 1–3 endocarditis divided doses daily for at least 7 days, supplemented by benzylpenicillin Adults: 2mg/kg i.v. every 8 hours, 100000IU/kg (maximum 4 million IU) together with benzylpenicillin 3 million i.v. or i.m. every 4 hours and metronida- IU i.v. every 4 hours and cloxacillin 2g zole 12.5mg/kg (maximum 500mg) i.v. i.v. every 4 hours. every 8 hours (once clinical improve- Children: 2.5mg/kg (maximum 80mg) ment occurs, rectal formulations of i.v. every 8 hours, together with ben- metronidazole may be substituted). zylpenicillin 50000IU/kg (maximum For patients who are allergic to 3 million IU) i.v. every 4 hours and penicillins, benzylpenicillin should cloxacillin 50mg/kg (maximum 2g) i.v. be replaced by clindamycin 600mg every 4 hours. (children: 10mg/kg; maximum 450mg) Patients allergic to penicillins or with orally or i.v. every 6–8 hours. nosocomial infections Contaminated soft tissue injuries Adults: 2mg/kg i.v. every 8 hours, Adults: 5–7mg/kg i.v. or i.m. daily in together with vancomycin 1g i.v. every divided doses for 5–10 days, supple- 12 hours. mented by metronidazole 500mg i.v. Children: 2.5mg/kg (maximum 80mg) every 8 hours (once clinical improve- i.v. every 8 hours, together with van- ment occurs, oral or rectal formulations comycin 20mg/kg (maximum 1g) i.v. of metronidazole may be substituted) every 12 hours. and cloxacillin 2g i.v. or i.m. every 6 hours (once clinical improvement Endocarditis due to a-haemolytic occurs, cloxacillin 500mg orally every 6 streptococci hours may be substituted). Uncomplicated endocarditis Adults: 1mg/kg i.v. every 8 hours, Children: 7.5mg/kg i.v. or i.m. in 1–3 together with benzylpenicillin 3 million divided doses daily for 5–10 days, sup- IU i.v. every 4 hours for 2 weeks. plemented by metronidazole 12.5mg/kg

139 WHO Model Prescribing Information — Drugs used in bacterial infections

Gentamicin (continued) 7 days, together with cloxacillin 2g i.v. every 4 hours for 6 weeks. Children: 1mg/kg i.v. every 8 hours, Children: 1mg/kg i.v. every 8 hours together with benzylpenicillin for 7 days, together with cloxacillin 100000IU/kg (maximum 3 million IU) 50mg/kg (maximum 2g) i.v. every 4 i.v. every 4 hours for 2 weeks. hours for 6 weeks. Strains highly susceptible to benzyl- Culture-negative endocarditis penicillin (MIC 0.12mg/l) £ Adults: 1 mg/kg i.v. every 8 hours for Adults: 1mg/kg i.v. every 8 hours for 2 4–6 weeks, supplemented for 6 weeks by weeks, together with benzylpenicillin benzylpenicillin 3–4 million IU i.v. every 3 million IU i.v. every 4 hours for 4 weeks. 4 hours. Children: 1mg/kg i.v. every 8 hours for Children: 1 mg/kg i.v. every 8 hours for 2 weeks, together with benzylpenicillin 4–6 weeks, supplemented for 6 weeks by 100000IU/kg (maximum 3 million IU) benzylpenicillin 100 000 IU/kg (maxi- i.v. every 4 hours for 4 weeks. mum 4 million IU) i.v. every 4 hours. Strains resistant to benzylpenicillin Prosthetic valve endocarditis (MIC 0.25–1.0mg/l) = Adults: 1mg/kg i.v. every 8 hours, Adults: 1mg/kg i.v. every 8 hours for together with vancomycin 1g i.v. every 4–6 weeks, supplemented for 6 weeks 12 hours for 6 weeks. by either benzylpenicillin 3–4 million IU i.v. every 4 hours or ampicillin 2g i.v. Children: 1mg/kg i.v. every 8 hours, every 4 hours. together with vancomycin 40mg/kg (maximum 1g) i.v. in 2–4 divided doses Children: 1mg/kg i.v. every 8 hours daily for 6 weeks. for 4–6 weeks, supplemented for 6 weeks by either benzylpenicillin 100000 If infection due to a Gram-negative bac- IU/kg (maximum 4 million IU) i.v. every terial pathogen is suspected, the dose of 4 hours or ampicillin 50mg/kg (maxi- gentamicin should be increased to 2 mum 2g) i.v. every 4 hours. mg/kg i.v. every 8 hours. Endocarditis due to enterococci Neonatal meningitis Adults: 1mg/kg i.v. every 8 hours for Meningitis due to unknown pathogen 4–6 weeks, supplemented for 6 weeks by 2.5 mg/kg i.v. every 12 hours, together either benzylpenicillin 3–4 million IU i.v. with ampicillin 50 mg/kg (maximum 2 every 4 hours or ampicillin 2g i.v. every g) i.v. every 8 hours (neonates < 7 days: 4 hours. ampicillin 50 mg/kg (maximum 2 g) i.v. every 12 hours) for a total of 7–10 days. Children: 1mg/kg i.v. every 8 hours for 4–6 weeks, supplemented for 6 Meningitis due to Listeria weeks by either benzylpenicillin 100000 monocytogenes IU/kg (maximum 4 million IU) i.v. every 2.5 mg/kg i.v. every 12 hours, together 4 hours or ampicillin 50mg/kg (maxi- with ampicillin 50 mg/kg (maximum 2 mum 2g) i.v. every 4 hours. g) i.v. every 8 hours (neonates < 7 days: Endocarditis due to meticillin- ampicillin 50 mg/kg (maximum 2 g) i.v. susceptible Staphylococcus aureus every 12 hours) for a total of 3 weeks. Adults: 1mg/kg i.v. every 8 hours for Meningitis due to group B streptococci 2.5 mg/kg i.v. every 12 hours, together

140 Drugs with benzylpenicillin 50 000–75 000 Prophylaxis in contaminated surgery IU/kg (maximum 2 million IU) i.v. every Adults and children: 5mg/kg i.v., 4–6 hours (neonates < 7 days: benzyl- together with clindamycin 600mg i.v. at penicillin 50 000 IU/kg (maximum 2 induction of anaesthesia. million IU) i.v. every 8 hours) for a total of 3 weeks. Contraindications Brucellosis • Pregnancy. Adults: 5–7mg/kg i.v. every 24 hours • Myasthenia gravis. for 2 weeks, together with doxycycline 100mg orally every 12 hours for 6 weeks. Precautions Gentamicin should be administered only Children >8 years: 7.5mg/kg i.v. in 1–3 by trained health personnel and care divided doses daily for 2 weeks, together must be taken to ensure that the correct with doxycycline 2mg/kg (maximum dose and duration of treatment is not 100mg) orally every 12 hours for 6 weeks. exceeded. When possible, audiometry Children £8 years: 7.5mg/kg i.v. in 1–3 should be carried out. This is particularly divided doses daily for 2 weeks, together important in neonates, elderly patients with sulfamethoxazole 20mg/kg + tri- and patients with renal impairment or if methoprim 4mg/kg (maximum 800mg the course of treatment is for more than + 160mg) orally every 12 hours for 6 7 days. The patient should be monitored weeks. for renal toxicity or ototoxicity. Pro- longed treatment should be avoided. Tularaemia Adults and children: 1.5mg/kg i.v. or Adverse effects i.m. every 8 hours for 7 days. Adverse effects are generally dose- related and where possible treatment Plague courses should not be prolonged for Adults and children: 1.7mg/kg i.v. or more than 7 days. Vestibular and audi- i.m. every 8 hours for 7 days. tory damage and to a lesser extent, renal Initial empirical therapy for toxicity are the most serious adverse septicaemia effects. Rarely, hypomagnesaemia occurs Adults and children >5 years: 5–7mg/kg during prolonged therapy. Pseudomem- i.v. every 24 hours or 1.5mg/kg i.v. or branous colitis has also been reported. i.m. every 8 hours, supplemented by either cloxacillin 2g i.v. every 4–6 hours Drug interactions or cefazolin 1–2g i.v. every 8 hours or The risk of toxicity is increased when clindamycin 600mg i.v. every 8 hours or ethacrynic acid or furosemide is admin- chloramphenicol 750mg i.v. every 6 istered concomitantly. hours. The action of neuromuscular-blocking Neonates: 2.5mg/kg i.v. every 12 hours, agents may be potentiated. together with ampicillin 50mg/kg (maximum 2g) i.v. every 8 hours Storage (neonates <7 days: ampicillin 50mg/kg Preparations for injection should be (maximum 2g) i.v. every 12 hours). stored in vials. Solutions are stable for up to 24 hours in most infusion fluids. Injec- tions should not be mixed with other drugs in the same syringe.

141 WHO Model Prescribing Information — Drugs used in bacterial infections

Imipenem + cilastatin Powder for injection, 250mg (as monohydrate) + 250mg (as sodium salt), 500mg (as monohydrate) + 500mg (as sodium salt) in vial

Children: 60mg/kg (maximum 2g) daily General information in 4 divided doses by i.v. infusion. Imipenem is a semisynthetic carbape- Treatment should be continued until at nem antibiotic produced by Streptomyces least 2 days after resolution of signs and cattleya, while cilastatin is a specific symptoms of infection. inhibitor of dihydropeptidase. Imipenem is inactivated by metabolism in the Contraindications kidney and is potentially toxic to renal tubules; its combination with cilastatin • Hypersensitivity to imipenem or prevents both renal inactivation and cilastatin. toxicity. • Breastfeeding. After intravenous infusion, imipenem + Precautions cilastatin is distributed widely through- The dosage should be reduced in out the body and is excreted in the urine patients with renal impairment or both as unchanged drug and as metabolites. central nervous system disorders.

Use in pregnancy Clinical information Imipenem should not be withheld in life- Uses threatening infections when the need of Treatment of nosocomial pneumonia the mother outweighs any possible risk due to multiresistant Staphylococcus to the fetus. aureus, Pseudomonas aeruginosa and Acinetobacter spp. Drug interactions Increased toxicity with antivirals such as Dosage and administration aciclovir has been reported. The dosage is expressed in terms of the imipenem component. Storage Powder for injection should be stored in Adults: 1–2g daily in 3–4 divided doses well-closed containers. After reconstitu- by i.v. infusion. tion, the solution is stable for up to 10 hours.

Metronidazole Tablet, 200mg, 250mg, 400mg, 500mg Oral suspension, 200mg (as benzoate)/5ml

against anaerobic bacteria and some pro- General information tozoa, including Trichomonas vaginalis. Metronidazole is a 5-nitroimidazole de- Metronidazole is almost completely rivative with antimicrobial activity absorbed after oral administration. Its

142 Drugs plasma half-life is about 8 hours and it is Aspiration pneumonia and lung excreted, largely in the urine, both abscesses unchanged and as metabolites. Adults: 500mg i.v. every 8–12 hours for 10–14 days (once clinical improvement occurs, 400mg orally every 12 hours may Clinical information be substituted), supplemented by ben- Uses zylpenicillin 1–2 million IU i.v. or i.m. every 4–6 hours. Treatment of: • aspiration pneumonia, lung abscesses Children: 12.5mg/kg (maximum 500mg) and brain abscess, together with ben- i.v. every 8–12 hours for 10–14 days (once zylpenicillin clinical improvement occurs, 10mg/kg • gingival infections and periodontitis (maximum 400mg) orally every 12 hours • amoebiasis, together with diloxanide may be substituted), supplemented by furoate benzylpenicillin 50000–100000IU/kg • giardiasis and necrotizing enterocoli- (maximum 2 million IU) i.v. or i.m. every tis due to Clostridium difficile 4–6 hours. • acute gastritis and peptic ulcer disease Gingival infections and periodontitis in adults, together with bismuth salicy- Adults: 400–500mg orally every 12 hours late plus either tetracycline or amoxi- for 5 days. cillin, or omeprazole plus amoxicillin • acute peritonitis, together with ampi- Children: 10–12.5mg/kg (maximum cillin and gentamicin 250mg) orally every 12 hours for 5 days. • gangrene, together with gentamicin and either benzylpenicillin or clin- Amoebiasis damycin Adults: 10mg/kg (maximum 250mg) • contaminated soft tissue injuries, orally every 8 hours for 8–10 days, fol- together with cloxacillin and genta- lowed by diloxanide furoate 500mg micin orally every 8 hours for 10 days. • human and animal bites and Children: 10mg/kg (maximum 250mg) clenched-fist injuries in patients al- orally every 8 hours for 8–10 days, fol- lergic to penicillins, together with lowed by diloxanide furoate 6–7mg/kg doxycycline or sulfamethoxazole + (maximum 500mg) orally every 8 hours trimethoprim for 10 days. • trichomoniasis and bacterial vaginosis in adults Giardiasis • pelvic inflammatory disease in adults Adults: 2g orally every 24 hours for 3 (ambulatory patients), together with days. ceftriaxone and doxycycline • moderate and severe pelvic inflam- Children: 30mg/kg (maximum 1.2g) matory disease in adults (hospitalized orally every 24 hours for 3 days. patients), together with ciprofloxacin Necrotizing enterocolitis due to and doxycycline. Clostridium difficile Prophylaxis in contaminated surgery, Adults: 200mg orally every 8 hours for together with cefazolin. 7–14 days. Children: 12.5mg/kg (maximum 200mg) Dosage and administration orally every 8 hours for 7–14 days. Metronidazole should preferably be administered with or immediately after meals.

143 WHO Model Prescribing Information — Drugs used in bacterial infections

Metronidazole (continued) For patients who are allergic to penicillins, benzylpenicillin should be Acute gastritis and peptic ulcer replaced by clindamycin 600mg disease in adults (children: 10mg/kg; maximum 450mg) 200mg orally every 8 hours plus 400mg orally or i.v. every 6–8 hours. orally at night for 2 weeks, supple- mented by bismuth salicylate 107.7mg Contaminated soft tissue injuries (1 tablet) orally every 6 hours plus either Adults: 500mg i.v. every 8 hours for 5–10 tetracycline 500mg orally every 6 hours days (once clinical improvement occurs, or amoxicillin 500mg orally every 6 oral or rectal formulations may be sub- hours, or 400mg orally every 8 hours for stituted), supplemented by cloxacillin 2 weeks, supplemented by omeprazole 2g i.v. or i.m. every 6 hours (once 40mg orally every 24 hours plus amoxi- clinical improvement occurs, cloxacillin cillin 500mg orally every 8 hours. 500mg orally every 6 hours may be sub- stituted) and gentamicin 5–7mg/kg i.v. Acute peritonitis or i.m. daily in divided doses. Adults: 500mg i.v. every 8–12 hours for at least 7 days, supplemented by Children: 12.5mg/kg (maximum ampicillin 2g i.v. or i.m. every 6 hours 500mg) i.v. every 8 hours for 5–10 days and gentamicin 5–7mg/kg i.v. daily in (once clinical improvement occurs, oral divided doses. or rectal formulations may be substi- tuted), supplemented by cloxacillin Children: 12.5mg/kg (maximum 500mg) 25–50mg/kg (maximum 2g) i.v. or i.m. i.v. every 8–12 hours for at least 7 days, every 6 hours (once clinical improve- supplemented by ampicillin 50mg/kg ment occurs, cloxacillin 12.5–25mg/kg (maximum 2g) i.v. or i.m. every 6 hours (maximum 500mg) orally every 6 hours and gentamicin 7.5mg/kg i.v. in 1–3 may be substituted) and gentamicin divided doses daily. 7.5mg/kg i.v. or i.m. in 1–3 divided doses daily. For patients who are allergic to peni- cillins, ampicillin should be deleted from Human and animal bites and the above regimens. clenched-fist injuries in patients allergic to penicillins Gangrene Adults: 400–500mg orally every 12 hours Adults: 500mg i.v. every 8 hours for at for 5–10 days, supplemented by either least 7 days (once clinical improvement doxycycline 100mg orally every 24 hours occurs, rectal formulations may be sub- or sulfamethoxazole 800mg + trimetho- stituted), supplemented by benzylpeni- prim 160mg orally every 12 hours. cillin 4 million IU i.v. or i.m. every 4 hours and gentamicin 5–7mg/kg i.v. or Children >8 years: 10–12.5mg/kg (maxi- i.m. daily in divided doses. mum 250mg) orally every 12 hours for 5–10 days, supplemented by either doxy- Children: 12.5mg/kg (maximum 500mg) cycline 2mg/kg (maximum 100mg) i.v. every 8 hours for at least 7 days (once orally every 24 hours or sulfamethoxa- clinical improvement occurs, rectal for- zole 20mg/kg + trimethoprim 4mg/kg mulations may be substituted), supple- (maximum 800mg + 160mg) orally every mented by benzylpenicillin 100000 12 hours. IU/kg (maximum 4 million IU) i.v. or i.m. every 4 hours and gentamicin 7.5 Children £8 years: 10–12.5mg/kg (maxi- mg/kg i.v. or i.m. in 1–3 divided doses mum 250mg) orally every 12 hours for daily. 5–10 days, supplemented by sulfame-

144 Drugs thoxazole 20mg/kg + trimethoprim 4 Contraindications mg/kg (maximum 800mg + 160mg) • Known hypersensitivity to imida- orally every 12 hours. zoles. Trichomoniasis in adults • Pregnancy. 2g orally in a single dose. • Chronic alcohol dependence. Sexual partners should be treated Precautions simultaneously. Patients should be warned not to take Bacterial vaginosis in adults any alcohol during treatment since 400–500mg orally every 12 hours for 7 disulfiram-like reactions can occur. days. Adverse effects Pelvic inflammatory disease in In general, metronidazole is well toler- adults ated, but mild symptoms of headache, Ambulatory patients gastrointestinal irritation and a persis- 400–500mg orally every 8 hours, to- tent metallic taste are common. Less gether with doxycycline 100mg orally frequently, drowsiness, rashes and every 12 hours for 10 days, following darkening of urine occur. initial therapy with ceftriaxone 250mg i.m. in a single dose. More serious reactions are rare and usually occur only during extended Hospitalized patients with moderate or courses of treatment. They include severe disease stomatitis and candidiasis, reversible 400–500mg orally every 8 hours, together leukopenia, and sensory peripheral with ciprofloxacin 500mg orally every 12 neuropathy, which is usually mild and hours for at least 4 days (or for 48 hours rapidly reversible. after clinical improvement occurs), fol- Ataxia and epileptiform seizures have lowed by doxycycline 100mg orally been reported among patients receiving every 12 hours for 10–14 days. dosages considerably higher than those Brain abscess currently recommended. Adults: 500mg i.v. every 8–12 hours, together with benzylpenicillin 3–4 Drug interactions million IU i.v. or i.m. every 4–6 hours. The action of oral anticoagulants is poten- tiated. Alcohol may induce abdominal Children: 12.5mg/kg (maximum 500mg) pain, vomiting, flushing and headache. i.v. every 8–12 hours, together with ben- zylpenicillin 100000IU/kg (maximum 3 Phenobarbital and corticosteroids lower million IU) i.v. or i.m. every 4–6 hours. plasma levels of metronidazole whereas cimetidine raises them. The duration of treatment depends on the clinical response and radiological Overdosage evidence of resolution of the abscess. No specific treatment exists. Emesis or Prophylaxis in contaminated surgery gastric lavage may be of value within a Adults and children: 500mg i.v., together few hours of ingestion. with cefazolin 1g i.v. at induction of anaesthesia (if the operation is prolonged Storage beyond 3–4 hours, a further 1-g dose of Tablets and suspension should be kept in cefazolin should be administered). well-closed containers, protected from light.

145 WHO Model Prescribing Information — Drugs used in bacterial infections

Nalidixic acid Tablet, 250 mg

Nalidixic acid should be administered General information cautiously to patients with epilepsy Nalidixic acid is a synthetic quinolone since seizures may be precipitated. antimicrobial which acts as a specific An adequate fluid intake must be inhibitor of bacterial DNA gyrase. It is ensured to prevent crystalluria. bactericidal against Enterobacteriaceae, including many strains of Shigella spp. Nalidixic acid has been shown to induce arthropathy in the weight-bearing joints It is rapidly and completely absorbed of young animals. It should only be used from the gastrointestinal tract. The in children if other agents are ineffective. plasma half-life is 1.5–8.0 hours and the drug is excreted in the urine, both Adverse effects unchanged and as metabolites. The most frequently reported adverse effects are nausea and vomiting. Visual disturbances, headache, rashes, pruritus, Clinical information urticaria, eosinophilia and photosensi- Uses tivity also occur occasionally. Treatment of shigellosis in adults and Hepatic and renal disturbances have also children ≥3 months. been reported.

Dosage and administration Drug interactions Adults: 1g orally every 6 hours for 5 A prolonged bleeding time has been days. reported in patients receiving anticoagu- Children ≥3 months: 15mg/kg (maxi- lants and nalidixic acid concurrently. mum 1g) orally every 6 hours for 5 days. Use of nalidixic acid may result in reduced susceptibility of Shigella spp. to Contraindications ciprofloxacin. • Hypersensitivity to any quinolone. • Age under 3 months. Overdosage • Pregnancy. Gastric lavage is of value if performed promptly. Electrolyte balance must be Precautions maintained. Anticonvulsants may be Reduced dosage should be considered needed for the treatment of seizures. in patients with hepatic or renal impairment. Storage Tablets should be stored in well-closed containers.

146 Drugs

Nitrofurantoin Tablet, 100mg

Men: 100mg orally every 12 hours for at General information least 14 days. Nitrofurantoin is a nitrofuran-type Prophylaxis against urinary tract antimicrobial with bacteriostatic activity infections in children against Escherichia coli and certain other 50mg orally at night. Gram-negative bacteria. Nitrofurantoin is readily absorbed from Contraindications the gastrointestinal tract. Between 20 and Patients with impaired renal function. 60% of the dose is bound to plasma pro- teins. It is partially metabolized in the Adverse effects liver and excreted in the urine. Thera- Nitrofurantoin is generally well toler- peutic concentrations are reached within ated at the doses used. The most 30 minutes of dosing. frequently reported adverse effect is nausea. If doses of 100mg every 6 hours are used, gastrointestinal symptoms may Clinical information be more severe. Uses Peripheral neuritis, pulmonary reac- Treatment of urinary tract infections in tions, hepatotoxicity and haematological adults. changes have been reported.

Prophylaxis against urinary tract infec- Storage tions in children. Tablets should be stored in well-closed containers. Dosage and administration Urinary tract infections in adults Women: 100mg orally every 12 hours for 3 days (for uncomplicated infections).

Nystatin Pessary, 100 000 IU

General information Clinical information Nystatin is an antifungal polyene anti- Uses biotic derived from Streptomyces noursei. Treatment of vaginal candidiasis. It is effective against infections caused by a wide range of yeasts and yeast-like Dosage and administration fungi. Vaginal candidiasis 200 000 IU as pessaries inserted high into the vagina nightly for 2 weeks (in some

147 WHO Model Prescribing Information — Drugs used in bacterial infections

Nystatin (continued) Use in pregnancy Safe use in pregnancy has not been geographical areas, nightly doses as high established. The need for treatment must as 1 million IU may be required). be determined by the condition of the mother. Administration should be continued for 48 hours after clinical cure. Higher doses and a longer period of treatment may Adverse effects be necessary in immunocompromised Irritation rarely occurs after topical patients. application.

Contraindications and Storage precautions Pessaries should stored below 15 °C in well-closed containers, protected from Treatment should be discontinued if light. symptoms of irritation or desensitization occur.

Phenoxymethylpenicillin Tablet, 250mg (as potassium salt) Powder for oral suspension, 250mg (as potassium salt)/5ml

streptococci in adults and children >2 General information years. Phenoxymethylpenicillin is a semisyn- • Postsplenectomy prophylaxis in adults thetic derivative of penicillin for oral use. and children >2 years. It is active against most Gram-positive bacteria but b-lactamase-producing Dosage and administration strains (mainly staphylococci) are Acute pharyngitis and acute cervical resistant. adenitis Adults: 500mg orally every 6 hours for It is well absorbed from the gastroin- 10 days. testinal tract and distributed widely in tissues. It is eliminated in the urine. It Children: 10–20mg/kg (maximum 500 crosses the placenta and is eliminated in mg) orally every 6 hours for 10 days. breast milk. Gingival infections and periodontitis Adults: 500mg orally every 6 hours for Clinical information 5 days. Uses Children: 10–20mg/kg (maximum 500 mg) orally every 6 hours for 5 days. • Treatment of acute pharyngitis, acute cervical adenitis, gingival infections, Tooth abscesses and suppurative periodontitis, tooth abscesses and odontogenic infections suppurative odontogenic infections. Adults: 500mg orally every 6 hours for • Prevention of recurrence of rheumatic 3 days. fever due to group A b-haemolytic

148 Drugs

Children: 10–20mg/kg (maximum 500 carefully about previous allergic reac- mg) orally every 6 hours for 3 days. tions before the first dose is adminis- tered. If a skin rash develops, the patient Prevention of recurrence of rheuma- should be transferred to a different class tic fever due to group A b-haemolytic of antimicrobial. streptococci and postsplenectomy prophylaxis in adults and children Use in pregnancy >2 years There is no evidence that phenoxy- Adults: 250mg orally every 12 hours. methylpenicillin is teratogenic. It may be Children >2 years: 125mg orally every used during pregnancy. 12 hours. Adverse reactions Contraindications Hypersensitivity reactions are most Known hypersensitivity to penicillins or common, ranging in severity from skin cefalosporins. rashes to immediate anaphylaxis. Mild diarrhoea can also occur. Precautions Facilities should be available for treating Storage anaphylaxis whenever penicillins are Preparations should be stored in well- used. Patients should be questioned closed containers.

Rifampicin Capsule or tablet, 150 mg, 300 mg

deacetylation in the liver are eventually General information excreted in the faeces. Rifampicin is a semisynthetic derivative Since resistance readily develops, of rifamycin, a complex macrocytic rifampicin must always be administered antibiotic that inhibits ribonucleic acid in combination with other effective anti- synthesis in a broad range of microbial mycobacterial agents. pathogens. Rifampicin is lipid-soluble. Following oral administration, it is rapidly ab- Clinical information sorbed and distributed throughout the Uses cellular tissues and body fluids; if the Treatment of: meninges are inflamed, significant • epiglottitis, together with chloram- amounts enter the cerebrospinal fluid. A phenicol or cefotaxime single dose of 600 mg produces a peak • meningitis due to benzylpenicillin- serum concentration of about 10 mg/ml resistant or ceftriaxone/cefotaxime- in 2–4 hours, which subsequently decays resistant Streptococcus pneumoniae, with a half-life of 2–3 hours. It is exten- together with vancomycin and cef- sively recycled in the enterohepatic cir- triaxone culation, and metabolites formed by • brucellosis, together with doxycycline or sulfamethoxazole + trimethoprim.

149 WHO Model Prescribing Information — Drugs used in bacterial infections

Rifampicin (continued) ceftriaxone 50–100 mg/kg (maximum 2 g) i.v. or i.m. every 12 hours. Prophylaxis against meningitis due to Neisseria meningitidis and Haemophilus Patients should be referred to a spe- influenzae. cialist. Brucellosis Dosage and administration Adults: 600 mg orally every 24 hours for Rifampicin should preferably be given 6 weeks, together with doxycycline 100 at least 30 minutes before meals, since mg orally every 12 hours. absorption is reduced when it is taken with food. Chidren > 8 years: 15 mg/kg (maximum 600 mg) orally every 24 hours for 6 Epiglottitis weeks, together with doxycycline 2 mg/ Adults: 600 mg orally every 24 hours for kg (maximum 100 mg) orally every 12 4 days, together with chloramphenicol hours. 1 g i.v. or i.m. every 6 hours for 5 days. Children £ 8 years: 15 mg/kg (maximum Children > 2 months: 20 mg/kg (maxi- 600 mg) orally every 24 hours for 6 mum 600 mg) orally every 24 hours for weeks, together with sulfamethoxazole 4 days, together with chloramphenicol 20 mg/kg + trimethoprim 4 mg/kg 25 mg/kg (maximum 1 g) i.v. or i.m. (maximum 800 mg + 160 mg) orally every 6 hours for 5 days. every 12 hours. Neonates aged 1–2 months: 20 mg/kg Prophylaxis against meningitis due (maximum 600 mg) orally every 24 hours to Neisseria meningitidis for 4 days, together with cefotaxime 50 Adults: 600 mg orally every 12 hours for mg/kg (maximum 2 g) i.v. or i.m. every 2 days. 8 hours for 5 days. Children ≥ 1 month: 10 mg/kg (maxi- Neonates < 1 month: 10 mg/kg (maxi- mum 600 mg) orally every 12 hours for 2 mum 300 mg) orally every 24 hours for 4 days. days, together with cefotaxime 50 mg/kg (maximum 2 g) i.v. or i.m. every 8 hours Neonates < 1 month: 5 mg/kg (maxi- for 5 days. mum 300 mg) orally every 12 hours for 2 days. In young children, consideration should be given to vaccination against H. influ- Prophylaxis should be considered for enzae serotype b. patients and their close contacts, espe- cially children under 5 years. Meningitis due to benzylpenicillin- resistant or ceftriaxone/cefotaxime- Prophylaxis against meningitis due resistant Streptococcus pneumoniae to Haemophilus influenzae Adults: 600 mg orally every 24 hours for Adults: 600 mg orally every 24 hours for at least 14 days, together with vanco- 4 days. mycin 1 g i.v. every 12 hours and cef- Children ≥ 1 month: 20 mg/kg (maxi- triaxone 2 g i.v. or i.m. every 12 hours. mum 600 mg) orally every 24 hours for 4 Children: 20 mg/kg (maximum 600 mg) days. orally every 24 hours for at least 14 days, Neonates < 1 month: 5 mg/kg (maxi- together with vancomycin 20 mg/kg mum 300 mg) orally every 24 hours for 4 (maximum 1 g) i.v. every 12 hours and days.

150 Drugs

Prophylaxis should be considered for tion. Temporary oliguria, dyspnoea and patients and their close contacts, espe- haemolytic anaemia have also been cially children under 5 years. reported. These reactions subside when daily dosage is instituted. Contraindications Moderate rises in serum concentrations • Known hypersensitivity to rifa- of bilirubin and transaminases, which mycins. are common at the onset of treatment, • Hepatic dysfunction. are often transient and without clinical significance. However, dose-related Precautions hepatitis can occur, which is potentially Serious immunological reactions result- fatal. It is consequently important not to ing in renal impairment, haemolysis or exceed the maximum recommended thrombocytopenia are on record in daily dose of 10 mg/kg (600 mg). patients who resume taking rifampicin after a prolonged lapse of treatment. In Drug interactions this rare situation it should be immedi- Rifampicin induces hepatic enzymes, ately and definitively withdrawn. and may increase the dosage require- ments of drugs metabolized in the liver. Careful monitoring of liver function is These include corticosteroids, steroid required in the elderly and in patients contraceptives, oral hypoglycaemic who are alcohol-dependent or have agents, oral anticoagulants, phenytoin, hepatic disease. cimetidine, quinidine, ciclosporin and Patients should be warned that treat- digitalis glycosides. ment may produce reddish discoloration Patients should consequently be advised of urine, tears, saliva and sputum, and to use a nonhormonal method of birth that contact lenses may be irreversibly control throughout treatment and for at stained. least 1 month subsequently. Use in pregnancy Biliary excretion of radiocontrast media Treatment should not be interrupted or and sulfobromophthalein sodium may postponed during pregnancy. be reduced and microbiological assays for folic acid and vitamin B disturbed. Vitamin K should be administered to the 12 infant at birth because of the risk of post- Overdosage partum haemorrhage. Gastric lavage may be of value if under- Adverse effects taken within a few hours of ingestion. Very large doses may depress central Rifampicin is well tolerated by most nervous function. There is no specific patients at currently recommended antidote and treatment is supportive. doses, although gastrointestinal intoler- ance can be unacceptably severe. Other Storage adverse effects (skin rashes, fever, Capsules and tablets should be kept in influenza-like syndrome and thrombo- tightly closed containers, protected from cytopenia) are more likely to occur with light. intermittent than with daily administra-

151 WHO Model Prescribing Information — Drugs used in bacterial infections

Spectinomycin Powder for injection, 2 g (as hydrochloride) in vial

If there is evidence of meningeal or General information endocardial involvement, treatment Spectinomycin is produced from Strepto- should be extended to 2 weeks and 4 myces spectabilis. It is most effective weeks, respectively. against Neisseria gonorrhoeae, in which it Gonococcal conjunctivitis selectively inhibits protein synthesis. Adults: 2 g i.m. in a single dose. It is rapidly absorbed after intramuscu- Neonates: 25 mg/kg (maximum 75 mg) lar injection and peak plasma concentra- in a single dose. tions occur after 1 hour. It is not significantly bound to plasma proteins Chancroid in adults and is excreted unchanged in the urine. 2 g i.m. in a single dose. (Longer treat- ment courses may be necessary in immunocompromised patients.) Clinical information Uses Contraindications Treatment of: Known hypersensitivity. • uncomplicated anogenital and dis- Precautions seminated gonococcal infections in In patients with renal impairment, adults spectinomycin should be used only • gonococcal conjunctivitis in adults when alternative therapies are inappro- and neonates priate. • chancroid in adults. Use in pregnancy Dosage and administration Since safety in pregnancy has not been All patients with gonorrhoea should be established, spectinomycin should be treated concurrently for chlamydial in- used in pregnant women only if the need fection unless microbiological facilities outweighs any possible risk to the fetus. exist to exclude the latter diagnosis. Sexual partners should be treated simul- Adverse effects taneously. Hypersensitivity reactions occur rarely. Uncomplicated anogenital gono- Pain at the injection site, nausea, fever, coccal infections in adults dizziness and urticaria have been 2 g i.m. in a single dose. reported. Disseminated gonococcal infections in adults Storage 2 g i.m. every 12 hours for 7 days. Powder for injection should be stored in vials.

152 Drugs

Streptomycin Powder for injection, 1 g base (as sulfate) in vial

Brucellosis in adults and children General information > 8 years Streptomycin is an aminoglycoside Adults: 1 g i.m. every 24 hours for 2 antibiotic derived from Streptomyces weeks, supplemented by doxycycline griseus that is used in the treatment 100 mg orally every 12 hours for 6 weeks. of tuberculosis and sensitive Gram- Children > 8 years: 15 mg/kg (maximum negative infections. 1 g) i.m. every 24 hours for 2 weeks, Streptomycin is not absorbed from the supplemented by doxycycline 2 mg/kg gastrointestinal tract but, after intramus- (maximum 100 mg) orally every 12 hours cular administration, it diffuses readily for 6 weeks. into the extracellular component of most Tularaemia body tissues and it attains bactericidal Adults and children: 15 mg/kg (maxi- concentrations, particularly in tubercu- mum 1 g) i.m. every 24 hours for 7–14 lous cavities. Little normally enters the days. cerebrospinal fluid, although penetra- tion increases when the meninges are Plague inflamed. The plasma half-life, which is Adults: 1 g i.m. every 12 hours for 7–10 normally 2–3 hours, is considerably days. extended in the newborn, in the elderly and in patients with severe renal impair- Children: 15 mg/kg (maximum 1 g) ment. It is excreted unchanged in the every 12 hours for 7–10 days. urine. Contraindications • Known hypersensitivity. Clinical information • Auditory nerve impairment. Uses • Myasthenia gravis. Treatment of: • Pregnancy. • brucellosis in adults and children > 8 Precautions years, together with doxycycline Should hypersensitivity reactions occur, • tularaemia as is common during the first weeks of • plague. treatment, streptomycin should be with- drawn immediately. Once fever and skin Dosage and administration rash have resolved, desensitization may Streptomycin must be administered by be attempted. deep intramuscular injection. Syringes and needles should be adequately steril- Streptomycin should be avoided, when ized, to exclude any risk of transmitting possible, in children because the injec- viral pathogens. tions are painful and irreversible audi- tory nerve damage may occur. Both the elderly and patients with renal impair- ment are also vulnerable to dose-related toxic effects resulting from accu- mulation. Serum levels should be

153 WHO Model Prescribing Information — Drugs used in bacterial infections

Streptomycin (continued) reduced by half immediately if urinary output falls, if albuminuria occurs or if monitored periodically and dosage tubular casts are detected in the urine. adjusted appropriately to ensure that plasma concentrations, as measured Haemolytic anaemia, aplastic anaemia, when the next dose is due, do not rise agranulocytosis, thromboctyopenia and above 4 mg/ml. lupoid reactions are rare adverse effects. Protective gloves should be worn when Drug interactions streptomycin injections are adminis- Other ototoxic or nephrotoxic drugs tered, to avoid sensitization dermatitis. should not be administered to patients receiving streptomycin. These include Use in pregnancy other aminoglycoside antibiotics, am- Streptomycin should not be used in photericin B, cefalosporins, etacrynic acid, pregnancy. It crosses the placenta and ciclosporin, cisplatin, furosemide and can cause auditory nerve impairment vancomycin. and nephrotoxicity in the fetus. Streptomycin may potentiate the effect Adverse effects of neuromuscular-blocking agents ad- Injections are painful and sterile ministered during anaesthesia. abscesses can form at injection sites. Hypersensitivity reactions are common Overdosage and can be severe. Haemodialysis can be beneficial. There is no specific antidote and treatment is Impairment of vestibular function is supportive. uncommon with currently recom- mended doses. Dosage should be Storage reduced if headache, vomiting, vertigo Solutions retain their potency for 48 and tinnitus occur. hours after reconstitution at room tem- Streptomycin is less nephrotoxic than perature and for up to 14 days when other aminoglycoside antibiotics. None refrigerated. Powder for injection should the less, close monitoring of renal func- be stored in tightly closed containers tion is necessary. Dosage must be protected from light.

Sulfadiazine Tablet, 500mg Injection, 250mg (sodium salt) in 4-ml ampoule

uted in the body. The serum half-life is General information 10–12 hours. After partial acetylation in Sulfadiazine is an intermediate-acting the liver it is excreted in the urine. sulfonamide with a broad spectrum of activity against a wide range of Gram- positive and Gram-negative organisms. Clinical information Uses Sulfadiazine is readily absorbed from the Prevention of recurrence of rheumatic gastrointestinal tract and widely distrib- fever due to group A b-haemolytic

154 Drugs streptococci in patients allergic to peni- in the mother. Their action in displacing cillins. bilirubin from protein-binding sites has given rise to concern, based on data Dosage and administration derived from premature neonates, that Adults: 1g orally or i.v. every 24 hours. they may promote kernicterus. Although sulfonamides readily cross the placental Children: 500mg orally or i.v. every 24 barrier there is no conclusive evidence hours. that the fetus is at risk.

Contraindications Adverse effects • Hypersensitivity to sulfonamides. Nausea, vomiting, diarrhoea and head- • Severe renal or hepatic dysfunction. ache sometimes occur. • Porphyria. Sulfonamide-induced hypersensitivity • Pregnancy during the third trimester. reactions, although uncommon, can be Precautions severe. They include rare life-threatening cutaneous reactions such as erythema The blood count should be monitored multiforme (Stevens–Johnson syn- twice weekly throughout therapy to drome) and toxic epidermal necrolysis. detect signs of bone-marrow depression. Administration should be discontinued Crystalluria may result in dysuria, renal immediately should presumptive signs colic, haematuria and acute renal of hypersensitivity occur, such as skin obstruction. rashes, dark urine and purpura. Any patient suspected of being sensitive to Other infrequent reactions include sulfonamides should never receive them granulocytopenia, thrombocytopenic again. purpura, agranulocytosis, aplastic anaemia and toxic hepatitis. Haemolysis Sulfadiazine is less soluble in urine than occasionally occurs in individuals many other sulfonamides. A high output deficient in glucose-6-phosphate of alkaline urine must be maintained dehydrogenase. during treatment to avoid crystalliza- tion. Patients should be advised to drink Overdosage 1.0–1.5 litres of alkaline water daily. Continuous forced diuresis may be ben- eficial and an alkaline urine should Concomitant administration of other be maintained. Treatment is otherwise drugs that interfere with folic acid symptomatic. metabolism (apart from pyrimethamine) should be avoided whenever possible. Storage Use in pregnancy Preparations should be stored protected from light. Administration of sulfonamides can induce severe hypersensitivity reactions

155 WHO Model Prescribing Information — Drugs used in bacterial infections

Sulfamethoxazole + trimethoprim Tablet, 100mg of sulfamethoxazole + 20mg of trimethoprim, 400mg of sulfamethoxazole + 80mg of trimethoprim, 800mg of sulfamethoxazole + 160 mg of trimethoprim Injection, 80mg of sulfamethoxazole + 16mg of trimethoprim/ml in 5-ml ampoule, 80mg of sulfamethoxazole + 16mg of trimethoprim/ml in 10-ml ampoule Oral suspension, 200mg of sulfamethoxazole + 40mg of trimethoprim in 5-ml vial

• melioidosis, together with ceftazidime General information • typhoid and paratyphoid fever, infec- The two components of this combination tious enteritis due to Salmonella en- product have a similar antimicrobial teritidis and enteritis due to entero- spectrum. They operate synergistically toxigenic Escherichia coli because they independently inhibit dif- • localized purulent skin lesions and ferent steps in the enzymic synthesis impetigo of tetrahydrofolic acid, an essential • human and animal bites and metabolic process in susceptible bacteria. clenched-fist injuries in patients aller- The combination enhances the antibac- gic to penicillins, together with metro- terial efficacy of the individual con- nidazole stituents and impedes the emergence of • osteomyelitis due to Salmonella spp. £ resistance. in children 5 years, together with cloxacillin and either ceftriaxone or Trimethoprim is absorbed more rapidly, cefotaxime is more widely distributed in tissues and • granuloma inguinale and meningitis enters the cerebrospinal fluid more due to Listeria monocytogenes in adults readily than sulfamethoxazole. Both • brucellosis in children £ 8 years, compounds are moderately bound to together with rifampicin or genta- plasma proteins and have a plasma half- micin. life of about 12 hours. The principal route of excretion is in the urine; approx- Dosage and administration imately 50% of the trimethoprim and Sulfamethoxazole + trimethoprim is between 15 and 30% of the sulfamethox- usually given orally, but in severe azole are recovered as unchanged drug. infections it can be administered intra- venously. Intravenous infusions should be administered in a 5% glucose solution Clinical information in water over 60 minutes. Oral dosage Uses forms should be substituted as soon as Treatment of: they can be ingested. • acute otitis media, acute sinusitis and Acute otitis media acute bronchitis Adults: sulfamethoxazole 400mg + • acute exacerbations of chronic bron- trimethoprim 80mg orally every 12 chitis and pneumonia due to Pneumo- hours for 5 days. cystis carinii in adults Children: sulfamethoxazole 20mg/kg • pneumonia in adults and children > 5 + trimethoprim 4mg/kg (maximum years and mild pneumonia in children 400mg + 80mg) orally every 12 hours aged from 2 months to 5 years for 5 days.

156 Drugs

Acute sinusitis Melioidosis Adults: sulfamethoxazole 400mg + Adults: sulfamethoxazole 1600mg + trimethoprim 80mg orally every 12 trimethoprim 320mg orally or i.v. every hours for 7–10 days. 12 hours for at least 14 days, supple- mented by ceftazidime 2g i.v. every 8 Children: sulfamethoxazole 20mg/kg hours. + trimethoprim 4mg/kg (maximum 400mg + 80mg) orally every 12 hours for Children: sulfamethoxazole 40mg/kg 7–10 days. + trimethoprim 8mg/kg (maximum 1600mg + 320mg) orally or i.v. every Acute bronchitis 12 hours for at least 14 days, supple- Adults: sulfamethoxazole 800mg + mented by ceftazidime 50mg/kg trimethoprim 160mg orally every 12 (maximum 2g) i.v. every 8 hours. hours for 5 days. After the initial intensive therapy, eradi- Children: sulfamethoxazole 20mg/kg + cation of any secondary infection is rec- trimethoprim 4mg/kg (maximum 800 ommended with oral sulfamethoxazole mg + 160mg) orally every 12 hours for 5 + trimethoprim for at least 3 months. days. Typhoid and paratyphoid fever, Acute exacerbations of chronic infectious enteritis due to Salmo- bronchitis in adults nella enteritidis and enteritis due to Sulfamethoxazole 800mg + trimetho- enterotoxigenic Escherichia coli prim 160mg orally every 12–24 hours Adults: sulfamethoxazole 800mg + for 5 days. trimethoprim 160mg orally every 12 Pneumonia in adults and children hours for 3 days. >5 years Children: sulfamethoxazole 20mg/kg Ambulatory patients + trimethoprim 4mg/kg (maximum Adults: sulfamethoxazole 800mg + 800mg + 160mg) orally every 12 hours trimethoprim 160mg orally every 12 for 3 days. hours for 5 days. Localized purulent skin lesions and Children >5 years: sulfamethoxazole impetigo 20mg/kg + trimethoprim 4mg/kg Adults: sulfamethoxazole 800mg + (maximum 800mg + 160mg) orally every trimethoprim 160mg orally every 12 12 hours for 5 days. hours for 5–7 days. Mild pneumonia in children aged Children: sulfamethoxazole 20mg/kg from 2 months to 5 years + trimethoprim 4mg/kg (maximum Sulfamethoxazole 20mg/kg + trimetho- 800mg + 160mg) orally every 12 hours prim 4mg/kg (maximum 800mg + for 5–7 days. 160mg) orally every 12 hours for 5 days. Human and animal bites and Pneumonia due to Pneumocystis clenched-fist injuries in patients carinii in adults allergic to penicillins Sulfamethoxazole 75mg/kg + trimetho- Adults: sulfamethoxazole 800mg + prim 15mg/kg i.v. or orally every 6–8 trimethoprim 160mg orally every 12 hours for 21 days. hours for 5–10 days, supplemented by metronidazole 400–500mg orally every 12 hours.

157 WHO Model Prescribing Information — Drugs used in bacterial infections

Sulfamethoxazole + Brucellosis in children £8 years trimethoprim (continued) Sulfamethoxazole 20mg/kg + trimetho- prim 4mg/kg (maximum 800mg + Children: sulfamethoxazole 20mg/kg 160mg) orally every 12 hours for + trimethoprim 4mg/kg (maximum 6 weeks, together with rifampicin 800mg + 160mg) orally every 12 hours for 15mg/kg (maximum 600mg) orally 5–10 days, supplemented by metronida- every 24 hours, or supplemented for the zole 10–12.5mg/kg (maximum 250mg) first 2 weeks by gentamicin 7.5mg/kg orally every 12 hours. i.v. in 1–3 divided doses daily.

Osteomyelitis due to Salmonella spp. Contraindications in children £5 years Children aged from 2 months to 5 years: • Known hypersensitivity to either sulfamethoxazole 20mg/kg + trimetho- component. prim 4mg/kg (maximum 800mg + • Severe hepatic or renal dysfunction. 160mg) orally every 12 hours to com- plete the treatment course of 6 weeks, Precautions following initial therapy with cloxacillin In HIV-infected patients with pneumo- 25–50mg/kg (maximum 2g) i.v. or i.m. nia due to Pneumocystis carinii whose every 4–6 hours and ceftriaxone 50–75 arterial oxygen tension is less than mg/kg (maximum 1g) i.v. or i.m. every 70mm Hg (9.33kPa), the risk of death 24 hours for 4–6 days (or until clinical during the first few days of treatment improvement occurs). can be substantially reduced if a corti- costeroid is administered as soon as Neonates: sulfamethoxazole 20mg/kg therapy is started. + trimethoprim 4mg/kg (maximum 800mg + 160mg) orally every 12 hours Treatment should be suspended imme- to complete the treatment course of 6 diately should a rash or any other weeks, following initial therapy with manifestation of sulfonamide hypersen- cloxacillin 25–50mg/kg (maximum 2g) sitivity occur. i.v. or i.m. every 4–6 hours and cefo- taxime 50–75mg/kg (maximum 2g) i.v. The risk of sulfonamide crystalluria is every 8 hours for 4–6 days (or until clin- decreased by maintaining a urinary ical improvement occurs). output of at least 1.5 litres daily. Whenever possible, plasma sulfonamide Granuloma inguinale in adults concentrations should be determined Sulfamethoxazole 800mg + trimetho- periodically. prim 160mg orally every 12 hours for 14 Patients must be advised to seek medical days (or until the lesion has completely advice should they develop a sore throat healed). or fever during treatment. This advice Meningitis due to Listeria monocyto- can be of greater value than routine genes in adults monitoring of the white cell count. Sulfamethoxazole 800mg + trimetho- Since elderly patients may be more sus- prim 160mg i.v. every 6 hours for at ceptible to severe adverse reactions, least 3 weeks. especially blood dyscrasias, their treat- Therapy often needs to be prolonged; ment should not be unnecessarily some patients may require treatment for prolonged. up to 6 weeks.

158 Drugs

Patients deficient in folate may require sionally occurs in individuals deficient supplementary calcium folinate to in glucose-6-phosphate dehydrogenase. prevent megaloblastic anaemia. Drug interactions Use in pregnancy Maintenance requirements for sulfonyl- Safe use in pregnancy has not ureas and coumarin anticoagulants are been established. Sulfamethoxazole + often reduced as a result of their dis- trimethoprim may be used, however, placement from plasma proteins by when the potential benefit to the mother sulfamethoxazole. outweighs any possible harm to the fetus. It should not be withheld in life- Concomitant use of other inhibitors of threatening diseases. folate metabolism (such as pyrimeth- amine, methotrexate and certain anti- Adverse effects convulsants) increases the risk of megaloblastic anaemia. The most common adverse effects are nausea, vomiting and skin rashes which Overdosage are mild and reversible. In patients with HIV infection receiving sulfamethoxa- Symptoms of acute overdosage include zole + trimethoprim for Pneumocystis vomiting, dizziness and confusion, fol- carinii pneumonia, recurrent fever, lowed by visual disturbances, petechiae, neutropenia, thrombocytopenia and purpura and jaundice. Crystalluria, increases in serum transaminase levels haematuria and anuria may also occur. also occur frequently. Emesis or gastric lavage may be of value Sulfonamide-induced hypersensitivity within a few hours of ingestion. Pro- reactions, although uncommon, can be vided urinary output is satisfactory, severe. They include life-threatening a high fluid intake should be main- cutaneous reactions such as erythema tained. Haemodialysis may be of value multiforme (Stevens–Johnson syn- in eliminating some of the drug. drome) and toxic epidermal necrolysis. Otherwise, treatment is symptomatic and supportive. Other infrequent reactions include leukopenia, neutropenia and thrombo- Storage cytopenia and less commonly, agranulo- Tablets, oral suspension and concentrate cytosis, megaloblastic anaemia, purpura for infusion should be stored, protected and toxic hepatitis. Haemolysis occa- from light, in well-closed containers.

Tetracycline Capsule or tablet, 250 mg of tetracycline hydrochloride Eye ointment, 1% tetracycline hydrochloride

tomyces. It induces bacteriostasis by General information inhibiting protein synthesis, and is Tetracycline is a broad-spectrum anti- selectively concentrated in susceptible biotic derived from a species of Strep- organisms.

159 WHO Model Prescribing Information — Drugs used in bacterial infections

Tetracycline (continued) Contraindications • Known hypersensitivity. Absorption occurs mainly from the • Severe renal impairment. stomach and small intestine. Peak • Pregnancy and early childhood (except plasma concentrations occur within 4 for topical use to prevent or treat hours and decay with a half-life of about gonococcal conjunctivitis in neonates). 8 hours. Excretion is primarily effected by filtration into the urine. Enterohepatic circulation results in high concentrations Precautions of tetracycline accumulating in the liver Troublesome oesophagitis may be aver- and bile. Bacteriostatic concentrations ted if the patient is propped up while are maintained for up to 6 hours after swallowing capsules or tablets and washes topical administration. them down immediately with a glass of water. Capsules and tablets should not be Tetracycline crosses the placenta and is taken with milk or with magnesium or excreted in breast milk. aluminium salts since these impair the absorption of tetracycline. Clinical information Time-expired capsules and tablets should be discarded. Degraded tetracycline has Uses been reported to induce renal dysfunc- • Treatment of acute gastritis and peptic tion indistinguishable from the Fanconi ulcer disease in adults, together with syndrome and skin lesions similar to bismuth salicylate and metronidazole. those of systemic lupus erythematosus. • Prevention and (when systemic treat- ment is not available) treatment of Use in pregnancy and early gonococcal conjunctivitis of the childhood newborn. Tetracycline is generally contraindicated in pregnancy and early childhood. Dosage and administration Because it is deposited in developing Acute gastritis and peptic ulcer teeth and bones and impairs skeletal cal- disease in adults cification, it can result in abnormal osteo- 500 mg orally every 6 hours for 2 weeks, genesis and permanent staining of teeth, supplemented by bismuth salicylate and occasionally causes hyperplasia of 107.7 mg (1 tablet) orally every 6 hours dental enamel. plus metronidazole 200 mg orally every 8 hours and 400 mg orally at night. Adverse effects Gastrointestinal irritation is common, as Gonococcal conjunctivitis in is depletion of the normal bowel flora, neonates permitting overgrowth of resistant or- Prevention: a single application of the ganisms. Irritative diarrhoea should ointment immediately after birth should be differentiated from enteritis due be sufficient. to suprainfection, particularly with coagulase-positive staphylococci, and Treatment: ointment should be instilled from pseudomembranous colitis due to into each eye hourly pending referral of Clostridium difficile. the infant. Phototoxic reactions occasionally result in porphyria-like skin changes and pig- mentation of the nails.

160 Drugs

Hypersensitivity reactions are rare. Mor- reported in patients who have received billiform rashes, urticaria, fixed drug a halogenated anaesthetic agent while eruptions, exfoliative dermatitis, cheilo- taking tetracyclines. sis, glossitis, pruritus and vaginitis have been reported, as have angioedema, ana- Storage phylaxis and pseudotumour cerebri. Tetracycline capsules, tablets and oint- ment should be kept in well-closed con- Drug interactions tainers, protected from light. The action of oral anticoagulants may be potentiated. Severe renal failure has been

Tinidazole Tablet, 500 mg

Adverse effects General information In general, tinidazole is well tolerated, Tinidazole is a 5-nitroimidazole deriva- but mild symptoms of headache, gas- tive with antimicrobial activity against trointestinal irritation and a persistent anaerobic bacteria and certain protozoa. metallic taste are common. Less fre- It is almost completely absorbed after quently, drowsiness, rashes and darken- oral administration. It is excreted largely ing of urine occur. in the urine, both unchanged and as More serious reactions are rare and usually metabolites. occur only during extended courses of treatment. They include stomatitis and candidiasis, reversible leukopenia, and Clinical information sensory peripheral neuropathy, which is Uses usually mild and rapidly reversible. Treatment of giardiasis. Ataxia and epileptiform seizures have been reported among patients receiving Dosage and administration dosages considerably higher than those Adults: 2 g orally in a single dose. currently recommended. Children: 50 mg/kg (maximum 2 g) orally in a single dose. Drug interactions The action of oral anticoagulants is poten- Contraindications tiated. Alcohol may induce abdominal pain, vomiting, flushing and headache. • Hypersensitivity to azole derivatives. • Pregnancy. Overdosage • Chronic alcohol dependence. No specific treatment exists. Emesis or gastric lavage may be of value within a Precautions few hours of ingestion. Patients should be warned not to take any alcohol during treatment since Storage disulfiram-like reactions can occur. Tablets should be kept in well-closed containers, protected from light.

161 WHO Model Prescribing Information — Drugs used in bacterial infections

Trimethoprim Tablet, 100mg, 200mg

Precautions General information Trimethoprim should be used with Trimethoprim is an inhibitor of folic acid caution in patients with folate deficiency, metabolism that is active against many since haematological changes can occur. Gram-positive cocci and Gram-negative Folinic acid should be administered to bacilli. these patients. Trimethoprim is well absorbed from the Use in pregnancy gastrointestinal tract and widely distrib- Safe use in pregnancy has not been uted in the tissues. It has a plasma half- established. Treatment should be life of about 11 hours and is excreted in deferred until after the first trimester of the urine. It crosses the placenta and is pregnancy. excreted in breast milk. Adverse effects The most frequent adverse effects are Clinical information skin rashes and urticaria. Uses Rarely, exfoliative dermatitis and toxic Treatment of urinary tract infections and epidermal necrolysis have been prostatitis in adults. observed. Gastrointestinal disturbances have also been reported. Haematological Dosage and administration reactions may occur in patients with Urinary tract infections in adults folate deficiency. Women: 300mg orally every 24 hours for 3 days (for uncomplicated infections). Drug interactions Men: 300mg orally every 24 hours for at Trimethoprim inhibits hepatic metabo- least 14 days. lism. Prostatitis in adults Overdosage 200mg orally every 12 hours for 4–6 Treatment is supportive and weeks. symptomatic.

Contraindications Storage • Pregnancy during the first trimester. Tablets should be stored in tightly closed • Renal impairment (creatinine clear- containers, protected from light. ance <15ml/minute). • Porphyria.

162 Drugs

Vancomycin Powder for injection, 500mg (as hydrochloride) in 10-ml vial, 250mg (as hydrochloride) in 5-ml vial

mial infections, and prosthetic valve General information endocarditis, together with genta- Vancomycin is a glycopeptide anti- micin biotic derived from Nocardia orientalis. • meningitis due to benzylpenicillin- It is bactericidal against a wide range resistant or ceftriaxone/cefotaxime- of Gram-positive organisms such as resistant Streptococcus pneumoniae, staphylococci, group A b-haemolytic together with ceftriaxone and streptococci, Streptococcus pneumoniae, rifampicin. enterococci, Corynebacterium spp. and Clostridium spp. including C. difficile. It is Dosage and administration not active against Gram-negative organ- Each i.v. dose should be dissolved in isms, fungi or yeasts. 100–200ml of dextrose and infused over 1 hour. After intravenous administration van- comycin is widely distributed in the When vancomycin is used in the treat- body tissues and diffuses readily into the ment of endocarditis, peak plasma pericardial, pleural, ascitic and synovial levels of 30–40mg/l and basal plasma fluids. It has a plasma half-life of 4–6 levels of 5–15mg/l are recommended. If hours and is excreted mainly in the urine gentamicin is used, basal plasma levels as unchanged drug. should not exceed 1mg/l. These levels are specific for the management of endo- carditis and do not apply to other Clinical information circumstances. Uses Pneumonia due to meticillin- Treatment of: resistant Staphylococcus aureus in adults and children >5 years • pneumonia due to meticillin-resistant Adults: 1g i.v. every 12 hours for 10–14 Staphylococcus aureus in adults and days. children > 5 years • nosocomial pneumonia due to Children >5 years: 20mg/kg (maximum meticillin-resistant Staphylococcus 1g) i.v. every 12 hours for 10–14 days. aureus, together with gentamicin plus either cloxacillin or ceftazidime, or Nosocomial pneumonia due to ciprofloxacin plus ceftazidime meticillin-resistant Staphylococcus • endocarditis due to meticillin- aureus resistant Staphylococcus aureus (MRSA) Adults: 1g i.v. every 12 hours for 10–14 • necrotizing enterocolitis due to days, supplemented for the first 7 days metronidazole-resistant Clostridium by gentamicin 5–7mg/kg i.v. daily difficile in divided doses plus either cloxacillin • endocarditis due to benzylpenicillin- 1Ò-2g i.v. every 6 hours orceftazidime resistant a-haemolytic streptococci 1g i.v. every 8 hours, or by cipro- and enterococci, infective endocarditis floxacin 500mg i.v. every 12 hours plus (initial empirical therapy) in patients ceftazidime 1g i.v. every 8 hours. allergic to penicillins or with nosoco-

163 WHO Model Prescribing Information — Drugs used in bacterial infections

Vancomycin (continued) Children: 40mg/kg (maximum 1g) i.v. in 2–4 divided doses daily, together with Children: 20mg/kg (maximum 1g) i.v. gentamicin 1mg/kg i.v. every 8 hours every 12 hours for 10–14 days, supple- for 6 weeks. mented for the first 7 days by gentamicin 7.5mg/kg i.v. in 1–3 divided doses If infection due to a Gram-negative daily plus either cloxacillin 50mg/kg pathogen is suspected, the dose of gen- (maximum 2g) i.v. every 6 hours or cef- tamicin should be increased to 2mg/kg tazidime 25mg/kg (maximum 1g) i.v. i.v. every 8 hours. every 8 hours, or by ciprofloxacin 10 Meningitis due to benzylpenicillin- mg/kg (maximum 300mg) i.v. every resistant or ceftriaxone/cefotaxime- 12 hours plus ceftazidime 25mg/kg resistant Streptococcus pneumoniae (maximum 1g) i.v. every 8 hours. Adults: 1g i.v. every 12 hours for at least Necrotizing enterocolitis due to 14 days, supplemented by ceftriaxone metronidazole-resistant Clostridium 2g i.v. or i.m. every 12 hours and difficile rifampicin 600mg orally every 24 hours. Adults: 125mg orally every 6 hours for Children: 20mg/kg (maximum 1g) i.v. 7–14 days. every 6 hours for at least 14 days, sup- Children: 5mg/kg (maximum 125mg) plemented by ceftriaxone 50–100mg/kg orally every 6 hours for 7–14 days. (maximum 2g) i.v. or i.m. every 12 hours and rifampicin 20mg/kg (maximum Endocarditis due to benzylpenicillin- 600mg) orally every 24 hours. resistant a-haemolytic streptococci and enterococci and initial empirical Patients should be referred to a specialist. therapy for infective endocarditis in patients allergic to penicillins or Contraindications with nosocomial infections Known hypersensitivity to vancomycin. Adults: 1g i.v. every 12 hours, together with gentamicin 2mg/kg i.v. every 8 Precautions hours. Vancomycin must be used only in a hos- pital setting where plasma concentra- Children: 20mg/kg (maximum 1g) i.v. tions can be measured. every 12 hours, together with gentamicin 2.5mg/kg (maximum 80mg) i.v. every 8 Dosage should be adjusted in accordance hours. with the creatinine clearance rate in patients with impaired renal function. Endocarditis due to meticillin- resistant Staphylococcus aureus Use in pregnancy Adults: 1g i.v. every 12 hours for 6 Safe use in pregnancy has not been weeks. established. Treatment should not be Children: 40mg/kg (maximum 1g) i.v. withheld, however, in life-threatening in 2–4 divided doses daily for 6 situations. weeks. Adverse effects Prosthetic valve endocarditis If the drug is administered too rapidly, Adults: 1g i.v. every 12 hours, together an acute erythematous rash occurs. with gentamicin 1mg/kg i.v. every 8 hours for 6 weeks.

164 Drugs

Ototoxicity and nephrotoxicity may Overdosage occur, particularly when treatment is Limited information is available on the prolonged. acute toxicity of vancomycin. Treatment of overdosage is supportive. Drug interactions Ototoxicity and nephrotoxicity may be Storage exacerbated by concurrent administra- Powder for injection should be stored in tion of aminoglycosides and other oto- well-closed containers. toxic agents.

165 Index

Note: Page numbers in bold type indicate main discussions.

Abscesses soft tissue injuries 52, 95 brain 80, 102, 120, 145 surgical prophylaxis 88, 89, 95 lung 27–28, 95, 100, 124, 143 urinary tract infections 44, 95 muscle (pyomyositis) 50, 107, 108–109, Ampicillin 96–98 125, 127 adverse effects 98 peritonsillar 14 cholecystitis 42, 97 tooth 33–34, 93, 105, 148–149 contraindications 98 Acinetobacter spp., resistance 12 dosage and administration 97–98 Adenitis endocarditis 71–72, 97 acute cervical 34, 103, 105 mastoiditis 17, 97 amoxicillin 92 meningitis 77–79, 97–98 cefalexin 106–107 neonatal meningitis 78, 79–80, 98 erythromycin 134 neonatal pneumonia 26 phenoxymethylpenicillin 148 neonatal septicaemia 87, 98 Administration, drugs 7–8 overdosage 98 Allergies, penicillins 16, 94, 96, 125, 132 peritonitis 42, 97 Alternative drugs 13 precautions 98 Amoebiasis 37, 39–40, 143 pyelonephritis 45, 97 Amoxicillin 11, 92–94 typhoid/paratyphoid 38 bronchitis 20–21, 92 Animal bites 51–52, 95, 105 cellulitis/erysipelas 48, 93 doxycycline 132 contraindications 94 metronidazole 144–145 dosage and administration 92–93 sulfamethoxazole + trimethoprim gastritis/peptic ulcer 41, 92 157–158 Lyme disease 81, 93 Anthrax 83–84, 102, 131 osteomyelitis 53, 56, 57, 93 Antitoxin, diphtheria 19 otitis media 16, 92 Arthritis, septic, see Septic arthritis overdosage 94 Aspergillus fumigatus, HIV-associated perioral/dental infections 34, 93 pneumonia 27 pharyngitis 15, 92 Aspiration pneumonia 27–28, 95 pneumonia 22, 24–26, 28, 93 benzylpenicillin 100 postsplenectomy prophylaxis 91, 93–94 clindamycin 124 precautions 94 metronidazole 143 surgical prophylaxis 88 Amoxicillin + clavulanic acid 11, 94–96 Bacillus anthracis 83 bronchitis 21, 95 Bacteroides fragilis, aspiration pneumonia contraindications 96 27 dosage and administration 95 Benzathine benzylpenicillin 103–104 osteomyelitis 55, 95 chancroid 67 otitis media 16, 95 diphtheria 19 overdosage 96 pharyngitis 14 pneumonia 28, 95 rheumatic fever prophylaxis 89, 90 precautions 96 syphilis 66

166 Index

Benzylpenicillin 6, 99–103 Campylobacter spp., invasive diarrhoea adverse effects 103 36–37, 122, 135 anthrax 84, 102 Candida albicans brain abscess 80, 102 endocarditis 72, 73 cellulitis/erysipelas 48, 100 HIV-associated pneumonia 27 contraindications 102 vaginitis 64, 147–148 dosage and administration 99–102 Candidiasis 64, 147–148 endocarditis 69–72, 97, 101 Capnocytophaga canimorsus, animal bites gangrene 49, 50, 100 51 leptospirosis 82, 102 Cardiovascular infections (see also Lyme disease 81, 102 Endocarditis; Rheumatic fever) 69–74 meningitis 75–79, 101–102 Carriers, typhoid/paratyphoid 38, 97 neonatal meningitis 80, 102 Cefalexin 106–108 osteomyelitis 53, 100 adverse effects 108 overdosage 103 cellulitis/erysipelas 48, 107 pneumonia 23–25, 28, 99–100 cervical adenitis 34, 106–107 precautions 102 contraindications 107 streptococcal necrotizing fasciitis 49, dosage and administration 106–107 100 osteomyelitis 53, 54, 107 syphilis 67, 100–101 pharyngitis 15, 106–107 Bismuth salicylate, gastritis/peptic ulcer purulent skin lesions 47, 48, 107 41 pyomyositis 50, 107 Bites septic arthritis 58, 59, 107 human/animal 51–52, 95, 105 substitutes 13 doxycycline 132 urinary tract infections 43, 44, 107 metronidazole 144–145 Cefalosporins 6, 11–12, 106–107 sulfamethoxazole + trimethoprim Cefazolin 108–109 157–158 adverse effects 109 Bone infections (see also Osteomyelitis; cellulitis/erysipelas 48, 108 Septic arthritis) 53–60 contraindications 109 Bordetella pertussis 31 osteomyelitis 53, 54, 109 Borrelia burgdorferi, Lyme disease 81 pneumonia 28, 108 Borrelia recurrentis, relapsing fever 81 pyomyositis 50, 108–109 Brain abscesses 80, 145 septicaemia 87, 109 benzylpenicillin 102 septic arthritis 58, 59, 109 chloramphenicol 120 substitutes 13 Bronchiectasis 21 surgical prophylaxis 88, 89, 109 Bronchitis 20–21, 157 Cefotaxime 110–111 amoxicillin 92, 95 contraindications 111 doxycycline 131 croup 110 Brucella spp. 34, 82 gonorrhoea 62 Brucellosis 82–83, 133 meningitis 11–12, 76–77 gentamicin 141 neonatal epiglottitis 18, 110 streptomycin 153 neonatal gonococcal conjunctivitis 111 sulfamethoxazole + trimethoprim 158 neonatal meningitis 79, 111 Burkholderia pseudomallei, melioidosis 31 neonatal pneumonia 26, 110 osteomyelitis 55, 56, 110–111 Calymmatobacterium granulomatis, septicaemia 87, 111 granuloma inguinale 68 septic arthritis 58, 60, 111

167 WHO Model Prescribing Information — Drugs used in bacterial infections

Ceftazidime 112–113 doxycycline 133 hospital-acquired pneumonia 30, 112 epiglottitis 18–19, 150 melioidosis 32, 112 impetigo 47–48 Pseudomonas aeruginosa 12 osteomyelitis 54–57, 93, 95, 158 Ceftriaxone 113–116 pneumonia 22–26 chancroid 67, 115 pneumonia drugs 93, 99–100, 105, 119, contraindications 116 135 croup 114 septic arthritis 107, 115 dosage and administration 114–116 typhoid/paratyphoid carriers 97 drug interactions 123 urinary tract infections 44, 95 epiglottitis 18, 114 Chlamydia pneumoniae, pneumonia 22 gonorrhoea 61, 62, 115 Chlamydia psittaci, ornithosis 31 Lyme disease 81, 116 Chlamydia trachomatis mastoiditis 17, 114 neonatal pneumonia 25 meningitis 11–12, 75–78, 115–116 prostatitis 46, 132, 135 osteomyelitis 54–56, 114–115 sexually transmitted diseases 62–63, 64 overdosage 123 Chlamydial infections 61 pelvic inflammatory disease 64, 65, 115 doxycycline 132 pneumonia 23, 25, 114 erythromycin 135–136 pyelonephritis 45, 114 ophthalmia 63, 135 septicaemia 87, 116 Chloramphenicol 6, 117–121 septic arthritis 58, 59, 115 adverse effects 120 substitutes 13 brain abscess 80, 120 Cefuroxime 11, 23, 117 childhood suppurative lung disease 21, Cellulitis 48, 93, 100 119 cefalexin 107 contraindications 120 cefazolin 108 dosage and administration 118–120 procaine benzylpenicillin 104 drug interactions 121 Central nervous system infections (see also epiglottitis 18, 118 Brain abscesses; Meningitis) 75–80 granuloma inguinale 68, 119 Cervical adenitis 34, 92, 105 mastoiditis 17, 118 benzathine benzylpenicillin 103 meningitis 75–76, 78, 119 cefalexin 106–107 plague 84, 120 erythromycin 134 pneumonia 23–26, 119 phenoxymethylpenicillin 148 relapsing fever 82, 120 Cervicitis 61, 63 rickettsial infections 85, 120 Chancroid 11, 12, 67–68 septicaemia 87, 120 ceftriaxone 115 severe croup 118 ciprofloxacin 122 tularaemia 83, 120 erythromycin 136 typhoid/paratyphoid 38, 119 spectinomycin 152 Cholecystitis 41–42, 97, 138 Chemoprophylaxis, see Prophylaxis Cholera 35, 122, 132 Children (see also Infants; Neonates) Cilastatin + imipenem, see Imipenem + brucellosis 158 cilastatin cervical adenitis 34, 105 Ciprofloxacin 12–13, 121–123 chronic suppurative lung disease 21, 92, anthrax 84, 123 119 chancroid 67, 122 ciprofloxacin 123 cholera 35, 122 congenital syphilis 66, 100–101, 106 contraindications 123

168 Index

dosage and administration 121–123 pneumonia 28–30, 127 drug interactions 123 prosthetic valve endocarditis 73 enteritis 37, 39, 122 purulent skin lesions 47, 127 gonorrhoea 61, 62, 122 pyomyositis 50, 127 hospital-acquired pneumonia 30, septicaemia 87, 130 121–122 septic arthritis 58, 59, 60, 129 legionellosis 27, 121 soft tissue injuries 51, 127–128 meningitis prophylaxis 76, 123 substitutes 13 osteomyelitis 54, 56–57, 122 Colds, common 15 overdosage 123 Colitis, see Enterocolitis pelvic inflammatory disease 65, 123 Combination therapy 4, 8–9 shigellosis 36 Common cold 15 substitutes 13 Computer software, WHONET 6 tularaemia 83, 123 Congenital syphilis 67, 100–101, 106 typhoid/paratyphoid 38, 122 Conjunctivitis urinary tract infections 45, 46 antibacterial drugs 111, 115, 135–136, Clavulanic acid + amoxicillin, see Amoxicillin 152, 160 + clavulanic acid chlamydial 63 Clenched-fist injuries 51–52, 95, 105 gonococcal 61–62 doxycycline 132 Corynebacterium diphtheriae metronidazole 144–145 cervical adenitis 34 sulfamethoxazole + trimethoprim pharyngitis 14 157–158 Corynebacterium spp., prosthetic valve Clindamycin 124–126 endocarditis 73 contraindications 126 Cost, treatment 8 dosage and administration 124–126 Cough drug interactions 126 chronic recurrent 21 gangrene 50, 125 whooping, see Pertussis lung abscesses 124 Coxiella burnetti 7 osteomyelitis 53, 54, 125 pneumonia 22 pelvic inflammatory disease 65, 125 Q fever 85 pneumonia 27, 28, 124 Croup (laryngotracheobronchitis) 18, 110, pyomyositis 50, 125 114, 118 septicaemia 87, 125 Cystic fibrosis 21 septic arthritis 58–59, 125 Cystitis 43, 44 streptococcal necrotizing fasciitis 49,125 Cytomegalovirus, HIV-associated pneumonia surgical prophylaxis 89, 126 27 Clostridium difficile, necrotizing enterocolitis 40, 143, 164 Data collection, drug resistance 6 Clostridium spp. Debridement, surgical 49, 51, 57 gangrene 49 Dental infections (see also Tooth abscesses) soft tissue injuries 51 33–34 Cloxacillin 126–130 Diarrhoeal disease 35–40 adverse effects 130 acute watery 35 contraindications 130 invasive (dysentery) 36–37 dosage and administration 127–130 persistent 37 endocarditis 69, 72, 129–130 Diloxanide furoate, amoebiasis 40 osteomyelitis 53–56, 128–129 Diphtheria 19 overdosage 130 benzathine benzylpenicillin 103

169 WHO Model Prescribing Information — Drugs used in bacterial infections

erythromycin 134–135 Enterobacteriaceae procaine benzylpenicillin 105 amoxicillin 92 Donovanosis, see Granuloma inguinale ampicillin 96 Dosage, principles 7 data collection 6 Doxycycline 131–134 pneumonia 25 anthrax 84, 131 resistance 10 bronchitis 20, 131 septic arthritis 57 brucellosis 82, 133 Enterococcus spp. cholera 35, 132 endocarditis 69, 71–72, 97, 140 contraindications 133 neonatal meningitis 79 dosage and administration 131–133 pyelonephritis 45 drug interactions 133–134 Enterocolitis, necrotizing 40, 143, 164 leptospirosis 82, 133 Epididymitis 63 Lyme disease 81, 133 Epiglottitis 18–19, 114 melioidosis 32, 131–132 chloramphenicol 118 ornithosis 31, 131 neonates 110 pelvic inflammatory disease 64–65, 132 Erysipelas 48, 93, 100 plague 84 cefalexin 107 pneumonia 23, 131 cefazolin 108 prostatitis 46, 132 procaine benzylpenicillin 105 Q fever 85, 131 Erythromycin 6, 134–136 relapsing fever 81, 133 cervical adenitis 34, 134 rickettsial infections 85, 133 chlamydial ophthalmia 63, 135 sexually transmitted diseases 63, contraindications 136 67–68, 132 diphtheria 19, 134–135 soft tissue injuries 52, 132 dosage and administration 134–136 Drug formularies 9, 10 drug interactions 136 Dysentery 36–37 enteritis 37, 135 gingival infections 33, 135 Eikenella corrodens, human bites 51 legionellosis 27, 135 Empyema 29 neonatal gonococcal conjunctivitis 136 Endocarditis 69–73 ointment 62 ampicillin 71–72, 97 ornithosis 31, 135 benzylpenicillin 101 overdosage 136 cloxacillin 129 pertussis 31, 135 culture-negative 72, 101 pharyngitis 15, 134 gentamicin 137–140 pneumonia 22–24, 135 a-haemolytic streptococci 69, 70–71, 97, postsplenectomy prophylaxis 91, 136 101, 139–140 prostatitis 46, 135 infective 69–72, 101 Q fever 85, 135 prosthetic valve 73, 140, 164 relapsing fever 82, 136 vancomycin 164 rheumatic fever prophylaxis 90–91, 136 Endometritis 63 sexually transmitted diseases 63, 67, Entamoeba histolytica, amoebiasis 39–40 135–136 Enteric infections 38–40 Escherichia coli Enteritis 36–37, 38–39 cholecystitis 41 ciprofloxacin 122 data collection 6 erythromycin 135 diarrhoeal disease 36, 37, 39, 122 sulfamethoxazole + trimethoprim 157 enteritis 157

170 Index

neonatal meningitis 79 tularaemia 83, 141 pneumonia 25, 27 Giardiasis 37, 40, 143 septicaemia 86 Gingival infections (see also Perioral urinary tract infections 43, 45 infections) 33, 105, 135, 143, 148 Essential Drugs, WHO Model List of 9–10, Glomerulonephritis, impetigo 47 11, 12, 13 Gonorrhoea 11, 12, 61–62, 63 Eye infections, see Chlamydial ophthalmia; ceftriaxone 115 Conjunctivitis ciprofloxacin 122 spectinomycin 152 Fasciitis, streptococcal necrotizing 49, Granuloma inguinale (donovanosis) 68, 119, 100, 125 132, 158 Fluoroquinolones 12–13, 121–123 Folliculitis 47 a-Haemolytic streptococci, endocarditis 69, Formularies 9, 10 70–71, 97, 101, 139–140 Francisella tularensis, tularaemia 83 b-Haemolytic streptococci, osteomyelitis 53, Fungal infection, endocarditis 72, 73 93, 100 Furunculosis 47 Haemophilus ducreyi, chancroid 67 Haemophilus influenzae Gangrene 49–50, 100 amoxicillin 11 clindamycin 125 chronic bronchitis 20 gentamicin 139 epiglottitis 18–19 metronidazole 144 gene transfer 3 Gardnerella vaginalis, vaginitis 64 infant facial lesions 48 Gastritis 41, 93, 144, 160 infant osteomyelitis 54–55, 95, 100, Gastrointestinal infections 114 diarrhoeal 35–40 meningitis 75, 77–78, 97, 116, 119 non-diarrhoeal 41–42 meningitis prophylaxis 97–98, 119, Gene transfer, antimicrobial resistance 3 150–151 Gentamicin 137–141 osteomyelitis 128 brucellosis 82–83, 141 otitis media 16 cholecystitis 42, 138 pneumonia 24 contraindications 141 septic arthritis 57 dosage and administration 137–141 sinusitis 17 drug interactions 141 Haemophilus spp., resistance 10 endocarditis 69–72, 137–140 Helicobacter pylori, gastritis/peptic ulcer 41 gangrene 50, 139 HIV infection meningitis 78–79 brain abscess 80 neonatal meningitis 78–80, 140–141 chancroid 67, 68 pelvic inflammatory disease 65, 139 gastrointestinal infections 37, 39 peritonitis 42, 138 pneumonia 27 plague 84, 141 sulfamethoxazole + trimethoprim pneumonia 23, 24, 26, 29–30, 138 precautions 158 precautions 141 Hospital-acquired infections 4–5, 13 prosthetic valve endocarditis 73 pneumonia 29–30, 112, 121–122, 127, pyelonephritis 45, 139 138, 163–164 resistance 12 septicaemia 86 septicaemia 87, 141 sources 29 soft tissue injuries 51, 139 Human bite injuries 51–52, 95, 105 surgical prophylaxis 88, 89, 141 doxycycline 132

171 WHO Model Prescribing Information — Drugs used in bacterial infections

metronidazole 144–145 benzylpenicillin 102 sulfamethoxazole + trimethoprim ceftriaxone 116 157–158 doxycycline 133 Lymphogranuloma venereum 62–63, 132, Imipenem + cilastatin 12, 30, 142 135 Impetigo 47–48, 157 cefalexin 107 Mastoiditis 17, 97, 114, 118 cloxacillin 127 Melioidosis 31–32, 131–132, 157 Infants (see also Children; Neonates) Men chlamydial ophthalmia 63 chlamydial infections 63 facial lesions 48 urinary tract infections 44 osteomyelitis 54–57, 95, 100, 114, 158 Meningitis 11–12, 26, 75–80 pneumonia 24–26, 100 ampicillin 77–79, 97–98 Infective endocarditis, see Endocarditis benzylpenicillin 75–80, 101–102 Injuries, see Bites; Clenched-fist injuries cefotaxime 11–12, 76–77, 79, 111 Intestinal infections, see Gastrointestinal ceftriaxone 11–12, 75–78, 115–116 infections chloramphenicol 75–76, 78, 119 Intrauterine devices (IUDs) 64 gentamicin 78–80, 140–141 Invasive diarrhoea (dysentery) 36–37 neonatal 78–80, 98, 102, 111, 140–141 IUDs, see Intrauterine devices neonatal pneumonia 26 Ixodes dammini, Lyme disease 81 otitis media/mastoiditis 16, 17 prophylaxis 76, 78, 97–98, 123, Joint infections (see also Septic arthritis) 150–151 53–60 rifampicin 76–78, 97–98, 150–151 sulfamethoxazole + trimethoprim 78, 158 Klebsiella spp. vancomycin 77, 164 aspiration pneumonia 27 Meticillin-resistant Staphylococcus aureus cholecystitis 41 (MRSA) 13, 30, 163–164 pyelonephritis 45 Metronidazole 142–145 amoebiasis 143 Laboratories, role of 5–7 aspiration pneumonia 28, 143 b-Lactam drugs 10–13, 69 brain abscess 80, 145 Laryngotracheobronchitis, see Croup contraindications 145 Legionella spp. 7, 22, 26 dosage and administration 143–145 Legionellosis 26–27, 121, 135 drug interactions 145 Leptospirosis 82 gangrene 50, 144 benzylpenicillin 102 gastritis/peptic ulcer 41, 144 doxycycline 133 giardiasis 143 Lesions, localized purulent skin 47, 107, gingival infections 33, 143 127, 157 lung abscesses 143 Listeria monocytogenes necrotizing enterocolitis 40, 143–144 meningitis 78–79 overdosage 145 meningitis drugs 98, 102, 140–141, 158 pelvic inflammatory disease 65, 145 Lung abscesses 27–28, 95, 100 peritonitis 42, 144 clindamycin 124 protozoal infections 40 metronidazole 143 soft tissue injuries 51, 52, 144–145 Lung disease, chronic suppurative 21, 92, surgical prophylaxis 88, 89, 145 119 trichomoniasis 145 Lyme disease 81, 93 vaginitis 64, 145

172 Index

Microflora, normal 4, 8 Nosocomial infections, see Hospital-acquired Model List of Essential Drugs (WHO) 9–10, infections 11, 12, 13 Nystatin 64, 147–148 Moraxella catarrhalis, chronic bronchitis 20 MRSA, see Meticillin-resistant Odontogenic infections 33–34, 105, Staphylococcus aureus 148–149 Mutations, resistant bacteria 4 Omeprazole, gastritis/peptic ulcer 41 Mycobacterium tuberculosis Ophthalmia, chlamydial 63, 135 cervical adenitis 34 Oral administration 7–8 pericarditis/myocarditis 73 Oral infections, see Perioral infections resistance 4, 6 Ornithosis (psittacosis) 31, 131, 135 Mycoplasma pneumoniae Osteomyelitis 53–57, 95, 158 bronchitis 20 benzylpenicillin 100 pneumonia 22 cefalexin 107 Myocarditis 73 cefazolin 109 ceftriaxone 114–115 Nalidixic acid 36, 146 ciprofloxacin 122 Nasopharyngitis 15 clindamycin 124 National reference laboratories 6 cloxacillin 128 Necrotizing enterocolitis 40, 143, 164 b-haemolytic streptococci 53, 93, 100 Necrotizing fasciitis, streptococcal 49, 100, neonates 55–57, 110–111, 158 125 Otitis media Neisseria gonorrhoeae acute 15–16, 92, 95, 158 gene transfer 3 chronic 16–17 resistance 6 septic arthritis 57 Paratyphoid fever 38, 97 sexually transmitted diseases 61–62, chloramphenicol 119 64 ciprofloxacin 122 spectinomycin 152 sulfamethoxazole + trimethoprim 157 Neisseria meningitidis Parenteral administration 7–8, 11 meningitis 75, 76, 101–102, 119 Pasteurella multocida, animal bites 51 prophylaxis 123, 150 Pathogens, identification 6–7 Neonates (see also Infants) Pelvic inflammatory disease 64–65, 115 ampicillin 26, 78–79, 87, 98 ciprofloxacin 123 cefotaxime 110–111 clindamycin 125 chlamydial ophthalmia 63 doxycycline 132 croup 110 gentamicin 139 epiglottitis 18, 110, 150 metronidazole 145 gonoccocal conjunctivitis 62, 111, 115, Penicillins 136, 152, 160 allergies 16, 94, 96, 125, 132 meningitis 78–80, 98, 102, 111, antimicrobial resistance 16, 24 140–141 Peptic ulcer disease 41, 93, 144, 160 osteomyelitis 55–57, 110–111, 158 Peptostreptococcus spp., aspiration pneumonia 25–26, 93, 110, 119, 138 pneumonia 27 septicaemia 87, 98 Pericarditis 73 septic arthritis 111 Periodontitis 33, 105 Neurosyphilis 66, 100, 105 erythromycin 135 Nitrofurantoin 43, 44, 147 metronidazole 143 Nocardia spp., brain abscess 80 phenoxymethylpenicillin 148

173 WHO Model Prescribing Information — Drugs used in bacterial infections

Perioral infections 33–34, 93, 105 clindamycin 126 Peritonitis 42, 97, 138, 144 doxycycline 133 Pertussis (whooping cough) 31, 135 gentamicin 141 Pharmacodynamics 7 rifampicin 151 Pharmacokinetics 7 sulfadiazine 155 Pharyngitis 14–15, 103, 106–107 urinary tract infections 43 amoxicillin 92 Prescribing, general principles 7–9 erythromycin 134 Primaquine, HIV-associated pneumonia 27 phenoxymethylpenicillin 148 Probenecid, syphilis 66 Phenoxymethylpenicillin 148–149 Procaine benzylpenicillin 104–106 cervical adenitis 148 cellulitis/erysipelas 48, 105 perioral/dental infections 33, 34 cervical adenitis 34, 105 pharyngitis 15 contraindications 106 postsplenectomy prophylaxis 91 diphtheria 19, 105 rheumatic fever prophylaxis 89, 90 dosage and administration 105–106 Plague 84–85, 120 perioral/dental infections 33, 34, 105 chloramphenicol 120 pneumonia 24, 25, 105 doxycycline 132 precautions 106 gentamicin 141 soft tissue injuries 52, 105 streptomycin 153 syphilis 66, 67, 105–106 Pneumocystis carinii, pneumonia 27, 124, Prophylaxis 157 meningitis 76, 78, 97–98, 123, 150–151 Pneumonia 21–30 neonatal gonococcal conjunctivitis 136 amoxicillin 22–26, 28, 93, 95 non-surgical 89–91 aspiration 27–28, 95, 100, 124, 143 postsplenectomy 91, 94, 136, 149 atypical 23 rheumatic fever 89–91, 104, 136, 149 benzylpenicillin 23–25, 28, 99–100 surgical 11–12, 88–89, 95, 109, 126, cefazolin 28, 108 141, 145 cefotaxime 26, 110 urinary tract infections 44, 147 ceftriaxone 23, 25, 114 Prostatitis 45–46, 63, 122 children 24–26, 100 doxycycline 132 chloramphenicol 23–26, 119 erythromycin 135 clindamycin 27, 28, 124 trimethoprim 162 cloxacillin 28–30, 127 Prosthetic implants doxycycline 23, 131 osteomyelitis 57 erythromycin 22–24, 135 surgical prophylaxis 88–89 gentamicin 23–24, 26, 29–30, 138 valve endocarditis 73, 140, 164 HIV infection 27 Proteus spp., pyelonephritis 45 hospital-acquired 29–30, 112, 121–122, Protozoal infections, intestinal 39–40 127, 138, 163–164 Pseudomonas aeruginosa legionellosis 26–27 data collection 6 neonates 25–26, 93, 110, 119, 138 prosthetic valve endocarditis 73 procaine benzylpenicillin 105 resistance 12 sulfamethoxazole + trimethoprim 157 septicaemia 86 vancomycin 163–164 Psittacosis, see Ornithosis Postsplenectomy prophylaxis 91, 94, 136, Publications, WHO 10 149 Punching injuries 51–52, 95, 105 Pregnancy doxycycline 132 ciprofloxacin 123 metronidazole 144–145

174 Index

sulfamethoxazole + trimethoprim osteomyelitis drugs 111, 115, 122, 157–158 128–129 Purulent skin lesions 47, 107, 127, 157 resistance 12 Pyelonephritis 45, 97, 114, 139 Salpingitis 63 Pyomyositis 50, 107, 108–109 Selection mechanisms, resistant bacteria clindamycin 125 3–4 cloxacillin 127 Septicaemia 86–87 ampicillin 98 Q fever 72, 85, 131, 135 cefazolin 109 Quality control, susceptibility testing 6 cefotaxime 111 ceftriaxone 116 Relapsing fever 81–82, 120, 133, 136 chloramphenicol 120 Reporting, surveillance data 5–7 clindamycin 125 Reserve antimicrobials 10–13 cloxacillin 130 Resistance (antimicrobial) 3–6, 9, 12–13 gentamicin 141 to benzylpenicillin 97 neonates 111 endocarditis pathogens 69–73, 164 Septic arthritis 57–60 to b-lactam drugs 10–12 cefalexin 107 meningitis pathogens 77, 150, 164 cefazolin 109 MRSA 13, 30, 163–164 ceftriaxone 115 to penicillins 16, 24 children 107, 115 Streptococcus pneumoniae 22, 24 clindamycin 125 Respiratory rates, pneumonia 21–22 cloxacillin 129 Respiratory tract infections 11–12 neonates 111 lower 20–30 Sexually transmitted diseases 61–68 upper 14–19 Shigella spp. 6, 36 Rheumatic fever 14, 73–74 Shigellosis 12, 36, 37, 122 secondary prophylaxis 89–90, 104, 136, Sickle-cell disease 39, 53 149 Sinusitis, acute 17, 92, 95, 158 Rhinitis 15 Soft tissue infections 47–52, 95, 107 Rickettsial infections 85, 120, 133 cloxacillin 127–128 Rifampicin 149–151 gentamicin 139 brucellosis 83, 150 metronidazole 144–145 contraindications 151 Software, WHONET 6 dosage and administration 150–151 Sources, hospital-acquired infections 29 drug interactions 151 Spectinomycin 152 epiglottitis 18–19, 150 chancroid 68 meningitis 77, 150 gonorrhoea 61, 62 meningitis prophylaxis 76, 78, 97–98, Splenectomy, post-, prophylaxis 91, 94, 136, 150–151 149 overdosage 151 Spontaneous mutation, resistant bacteria 4 Rocky Mountain spotted fever 85 Spotted fever 85 Staphylococcus aureus Salmonella spp. cardiovascular infections 69, 72, 73, data collection 6 129–130, 140 enteric infections 38–39, 119, 122, cervical adenitis 34 157 data collection 6 infant osteomyelitis 158 meticillin-resistant (MRSA) 13, 30, osteomyelitis 53, 54, 56–57 163–164

175 WHO Model Prescribing Information — Drugs used in bacterial infections

neonatal osteomyelitis 111 overdosage 154 neonatal septic arthritis 111 plague 85, 153 osteomyelitis 53–56, 107, 109, 114, 125, tularaemia 83, 153 128 Sulfadiazine 91, 154–155 pneumonia 24–25, 28–29, 108, 124, Sulfamethoxazole + trimethoprim 6, 127, 138 156–159 prostatitis 45 bronchitis 20–21, 157 pyomyositis 50 brucellosis 83, 158 resistance 12 contraindications 158 septicaemia 86 dosage and administration 156–158 septic arthritis 57, 58–60, 107, 109, drug interactions 159 115, 125 enteric infections 38, 39 soft tissue injuries 51 granuloma inguinale 68, 158 surgery 88 HIV-associated pneumonia 27 Staphylococcus saprophyticus, urinary tract infant osteomyelitis 56, 57 infections 43 melioidosis 32, 157 Staphylococcus spp., prosthetic valve meningitis 78, 158 endocarditis 73 osteomyelitis 158 Streptococcal necrotizing fasciitis 49, 100, otitis media 16, 156 125 overdosage 159 Streptococcus anginosus (milleri), brain pneumonia 23, 25, 27, 157 abscess 80 precautions 158–159 Streptococcus pneumoniae purulent skin lesions 47, 48, 157 bronchitis 20–21 sinusitis 157 data collection 6 soft tissue injuries 52, 157–158 meningitis 75, 76–77, 79, 102, 116 typhoid/paratyphoid 157 otitis media 16 Surgery pneumonia 22, 24, 25 amoxicillin + clavulanic acid 95 resistance 11–12 cefazolin 109 septicaemia 86 chemoprophylaxis 11–12, 88–89, 126 septic arthritis 57 gentamicin 141 sinusitis 17 metronidazole 145 Streptococcus pyogenes Surveillance data, reporting 5–7 aspiration pneumonia 27 Susceptibility testing 5–7 cervical adenitis 34 Syphilis 61, 66–67 data collection 6 benzathine benzylpenicillin 103–104 impetigo 47 benzylpenicillin 100–101 necrotizing fasciitis 49 doxycycline 132 pharyngitis 14 erythromycin 136 rheumatic fever 73–74 procaine benzylpenicillin 105–106 soft tissue injuries 51 Streptococcus spp. Testing, antimicrobial susceptibility 6 bite injuries 51 Tetracycline 159–161 neonatal meningitis 79–80 contraindications 160 prosthetic valve endocarditis 73 dosage and administration 160 Streptomycin 153–154 drug interactions 161 brucellosis 82, 153 gastritis/peptic ulcer 41, 160 contraindications 153 neonatal gonococcal conjunctivitis 160 dosage and administration 153 ointment 62

176 Index

Tinidazole 40, 161 Vaginitis 64, 147–148 Tooth abscesses 33–34, 93, 105, 148–149 Vaginosis 145 Toxoplasma gondii, brain abscess 80 Vancomycin 13, 163–165 Treatments, options 9–13 contraindications 164 Treponema pallidum, syphilis 66 dosage and administration 163–164 Trichomonas vaginalis, vaginitis 64 endocarditis 69–72, 164 Trichomoniasis 64, 145 meningitis 77, 164 Trimethoprim 43, 46, 162 MRSA 163–164 Trimethoprim + sulfamethoxazole, see necrotizing enterocolitis 40, 164 Sulfamethoxazole + trimethoprim overdosage 165 Tularaemia 83, 120, 141, 153 pneumonia 29, 30, 163–164 Typhoid fever 12, 38, 97 prosthetic valve endocarditis 73 chloramphenicol 119 Vascular surgery, prophylaxis 88–89 ciprofloxacin 122 Vibrio cholerae 35 sulfamethoxazole + trimethoprim Viridans streptococci, pneumonia 27 157 Typhus fever 85 WHONET software 6 Whooping cough (pertussis) 31, 135 Upper respiratory tract infections 14–19 Women Ureaplasma urealyticum, prostatitis 46, 132, chlamydial infections 63 135 urinary tract infections 43–44 Urethritis 63 World Health Organization (WHO) Urinary tract infections 43–46, 95 Model List of Essential Drugs 9–10, 11, cefalexin 107 12, 13 nitrofurantoin 147 WHONET software 6 trimethoprim 162 Wounds (see also Bites; Soft tissue infections) Vaccination contaminated soft tissue 48, 51–52 epiglottitis 19 postsplenectomy prophylaxis 91 Yersinia pestis, plague 84

177