COMMON

DANA BARTLETT, RN, BSN, MSN, MA

Dana Bartlett is a professional nurse and author. His clinical experience includes 16 years of ICU and ER experience and over 20 years of as a poison control center information specialist. Dana has published numerous CE and journal articles, written NCLEX material, written textbook chapters, and done editing and reviewing for publishers such as Elsevire, Lippincott, and Thieme. He has written widely on the subject of toxicology and was recently named a contributing editor, toxicology section, for Critical Care Nurse journal. He is currently employed at the Connecticut Poison Control Center and is actively involved in lecturing and mentoring nurses, emergency medical residents and pharmacy students.

ABSTRACT

There are many antibiotics available in the United States to treat various forms of . Understanding the benefits and risks of therapy, such as adverse effects associated with specific antibiotics, and the safe administration and monitoring of patients receiving antibiotics can appear daunting. However, issues of antibiotic therapy may be approached by knowing the adverse effects common to all antibiotics, those at risk of having adverse effects and the level of severity of adverse effects as well as any testing required for detection. The main classes of antibiotics and the specific antibiotics available in the U.S., in particular, the , , , glycopeptide, lincosamide, , , quinolone, , , and nitrofurantoin antibiotics are discussed. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 1

Continuing Nursing Education Course Planners

William A. Cook, PhD, Director, Douglas Lawrence, MA, Webmaster, Susan DePasquale, CGRN, MSN, FPMHNP-BC, Lead Nurse Planner

Policy Statement

This activity has been planned and implemented in accordance with the policies of NurseCe4Less.com and the continuing nursing education requirements of the American Nurses Credentialing Center's Commission on Accreditation for registered nurses. It is the policy of NurseCe4Less.com to ensure objectivity, transparency, and best practice in clinical education for all continuing nursing education (CNE) activities.

Continuing Education Credit Designation

This educational activity is credited for 3 hours. Nurses may only claim credit commensurate with the credit awarded for completion of this course activity.

Pharmacology content is credited for 3 hours.

Statement of Learning Need

Properties of antibiotics influence medical guidelines for the treatment of an infectious process and follow up care in terms of antibiotic use and monitoring of treatment outcomes. The rise of antibiotic resistance poses a significant health risk, which health professionals must consider when deciding treatment in terms of antibiotic type and drug qualities. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 2

Course Purpose

To provide nurses with knowledge of common antibiotics, as well as the indications and the correct and safe administration of antibiotics.

Target Audience

Advanced Practice Registered Nurses and Registered Nurses

(Interdisciplinary Health Team Members, including Vocational Nurses and Medical Assistants may obtain a Certificate of Completion)

Course Author & Planning Team Conflict of Interest Disclosures

Dana Bartlett, RN, BSN, MSN, MA, William S. Cook, PhD, Douglas Lawrence, MA, Susan DePasquale, CGRN, MSN, FPMHNP-BC – all have no disclosures

Acknowledgement of Commercial Support

There is no commercial support for this course.

Activity Review Information

Reviewed by Susan DePasquale, CGRN, MSN, FPMHNP-BC

Release Date: 12/12/2015 Termination Date: 12/12/2018

Please take time to complete a self-assessment of knowledge, on page 4, sample questions before reading the article.

Opportunity to complete a self-assessment of knowledge learned will be provided at the end of the course. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 3

1. Antibiotic-associated diarrhea a. can have a delayed onset and cause serious complications. b. occurs after the first dose and is always mild and self-limiting. c. only occurs in women >age 60. d. typically affects hospitalized neonates.

2. Allergic reactions to antibiotics a. always happen within one hour after a dose. b. can be delayed in onset. c. are always severe and life-threatening. d. only occur in people who have a compromised immune system.

3. True or false: Someone who is allergic to penicillin may be allergic to . a. True b. False.

4. Patients who are receiving antibiotic therapy should be monitored for a. osteoporosis. b. polycythemia. c. diabetes mellitus. d. .

5. Which of these antibiotics is well known for causing ototoxicity? a. . b. Metronidazole. c. . d. Quinilones. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 4

Introduction

This learning module discusses antibiotic therapy as well as specific antibiotics. In particular, the aminoglycoside, carbapenem, cephalosporin, glycopeptide, lincosamide, macrolide, penicillin, quinolone, sulfonamide, and , and metronidazole and nitrofurantoin are covered in the following sections. Antibiotics that are not available in the United States will not be covered.

Specific aspects of antibiotic therapy raised in the following sections include:

1. 2. Considerations for administration 3. Adverse effects/warnings including the U.S. boxed warning, more common, i.e., >10% reporting rate, adverse effects of specific antibiotics, and, adverse effects or warnings that are reported for all of the antibiotics of a particular class (frequency of an adverse reaction not reported in commonly used drug reference sources is not discussed) 4. Labeled uses

In addition, issues that are important for the safe administration of antibiotics will be covered in this course: adverse effects common to all antibiotics, allergic reactions and cross-reactivity, and antibiotic resistance.

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Learning Break: The term antibiotic is defined as a drug that is used to treat an infection, but it is commonly used to refer to drugs that are used to treat bacterial . This is technically incorrect but, given the widespread and commonly accepted use of the term antibiotic in that context, its common use will be retained in this module.

Discussion of drug dosages, interactions, off-label uses, and all of the possible adverse effects of each antibiotic and/or class of antibiotics would not be practical here, and that information can easily be found in drug reference books and package inserts. Information that is particular to each of the antibiotic classes and important for safe administration will be the primary focus. The primary source of information is Lexi-Comp® or Lexi-Drugs® unless citations shown in the following sections specifically indicate otherwise.

A Boxed Warning, sometimes called a black box warning, is a warning that is required by the Food and Drug Administration (FDA) to be included and prominently featured in the prescribing information of a drug if there is potential for a severe adverse reaction (death, permanent disability, a life-threatening event) in proportion to the potential benefit of the drug, which requires cautious assessment of the drug’s risks and benefits; or if there is a serious adverse reaction that can be prevented or reduced in severity by appropriate use of the drug, i.e., patient selection, careful monitoring, avoiding certain concomitant therapy. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 6

Mechanism Of Antibiotic Action

Antibiotics are used to treat infections caused by susceptible and all of the antibiotics interfere with some aspect of the biochemical processes that are necessary for these microorganisms to survive. The mechanisms of action of antibiotics are quite complex and are specific to each class of antibiotic but the essential action of most antibiotics is disruption of the bacteria cell membrane, most often by inhibiting protein synthesis and making it impossible for the bacteria to maintain intracellular homeostasis. Antibiotics are not effective treatment for fungal or viral infections.

Adverse Effects

Reference books and package inserts provide extensive lists of adverse effects associated with and/or caused by a drug, but these information sources seldom quantify how likely it is that a specific adverse effect will occur or which patients are at risk. Clinicians want to know what adverse effects are of a practical concern and what to do about them, but the drug information references do not often provide this type of guidance. For example, package inserts for antibiotics warn that these drugs can cause and damage and should be used with caution if the patient has, or is at risk for, hepatic and/or renal impairment. The clinician wants to know how frequently and to whom these adverse effects will occur but very often this information is not given. A more specific example is that a commonly used drug information source lists 37 adverse effects associated with cephalexin; these range in severity from nausea to anaphylaxis and hemolytic

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anemia, but the incidence of any specific adverse effect is not mentioned.

Given the number of adverse effects caused by or reported to be associated with antibiotics, safely administering these drugs and monitoring patients for adverse effects can appear daunting, but this seemingly complex issue can be resolved by understanding the following aspects of antibiotic treatment. 1. The adverse effects that are common to all antibiotics, which are antibiotic-associated diarrhea, hepatic damage, and nephrotoxicity. 2. The patient populations that are at risk for these adverse effects. 3. Differentiating between adverse effects that are minor and severe and between the adverse effects that are observable and those that require special testing for detection.

Antibiotic-Associated Diarrhea

Antibiotics can alter the characteristics of the flora of the gut, and this can cause gastrointestinal problems. One of the most common adverse effects of antibiotic therapy is antibiotic-associated diarrhea.1,2 Package inserts of commonly used antibiotics state that the prevalence of antibiotic-associated diarrhea is not known, but it has been estimated to be between 3%-29% and a recent review of randomized controlled trials noted a prevalence of 14%.3

Children and the elderly are at greater risk for antibiotic-associated diarrhea than are other patient populations, and recent surgery, the nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 8

concomitant use of drugs that alter bowel motility, and the use of multiple antibiotics also increases the risk.2 Signs and symptoms begin from 1 to 16 days after initiation of therapy and the duration of antibiotic-associated diarrhea has been reported to be from 2 to 49 days with a median of 4 days.2

Most cases of antibiotic-associated diarrhea will resolve without sequelae, but package inserts and drug information resources for antibiotics note that prolonged use can alter gut flora and cause bacterial or fungal super-infection, resulting in serious illnesses such as C. difficile-associated diarrhea and pseudomembranous colitis.

Clostridium-difficile is a gram-positive bacillus that produces exotoxins and that can cause -difficile-associated diarrhea. Antibiotic use is the major risk factor for developing C. difficile infection.4 It is considered to be primarily a nosocomial infection,2,5 and approximately 10%-20% of all cases of antibiotic-associated diarrhea are caused by C. difficile.2 Almost all antibiotics can cause C. difficile-associated diarrhea, but , , the cephalosporins, , and the fluoroquinolones are the ones most associated with the disease.4 This is a potentially serious adverse effect of antibiotic therapy. Patients may have diarrhea for weeks, relapses are very common, and major complications such as death and sepsis are possible.5 Most cases of C. difficile diarrhea begin during antibiotic therapy or shortly after therapy has been stopped. However, the onset of C. difficile-associated diarrhea can be two to three months after antibiotic therapy has finished.6

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Pseudomembranous colitis is an inflammatory bowel disease that is usually caused by antibiotic use, most often with ampicillin, the cephalosporins, clindamycin, and ,7 but any antibiotic can be a causative agent. Pseudomembranous colitis complicates approximately 10% of all cases of antibiotic-associated diarrhea,7 and the mortality rate in patients who are elderly and/or have serious complications such as toxic megacolon can be as high as 35%.7

Allergic Reactions

Allergic reactions to antibiotics are prominently mentioned in drug information resources. Asking a patient if he/she has an allergy to any antibiotics is part of taking a health history and is routinely done before giving someone the first dose of an antibiotic. Allergic reactions are a type of hypersensitivity reaction that are mediated through the immune system.8 There are different ways of classifying allergic reactions, but a common and useful way to do so is based on when the allergic reaction appears immediate or delayed.9

Immediate allergic drug reactions may begin within minutes of drug administration and usually occur within one hour. However, if the patient has been given an oral antibiotic, has recently eaten, or if the absorption of the drug is delayed the onset can begin past the one hour mark.8,9

An immediate allergic reaction may cause mild signs and symptoms such as pruritus and rash or more serious effects such as angioedema, bronchospasm, hypotension, or anaphylaxis and death. Anaphylaxis is nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 10

the most feared allergic drug reaction but fortunately it is an uncommon occurrence. It has been estimated that there are one to four cases of anaphylaxis caused by penicillin for every 10,000 doses administered9 and anaphylactic reactions to cephalosporins and carbapenems are rare.10,11

Delayed allergic drug reactions happen after antibiotic therapy has been ongoing for days or weeks. The onset of signs and symptoms may also occur several days after the patient has stopped taking the antibiotic. Delayed allergic drug reactions are more common than the immediate type.9

Table 1: Risk Factors for Penicillin and Antibiotic Allergy9,12

Age: Patients between the ages of 20-49 appear to be most at risk for having an immediate reaction or an anaphylactic reaction to penicillin.

Allergies to other .

Hereditary factors: There is evidence that an allergy to penicillin can be inherited, but first-degree relatives of someone who is allergic to penicillin do not need to avoid taking the drug.

Occupational exposure: People who are exposed to penicillin at their workplace can be sensitized to the drug.

Repeated exposures to .

Route of exposure: Parenteral administration is more likely to cause anaphylaxis.

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The incidence of penicillin and antibiotic allergies is unclear. It has been reported that between 5%-10% of the population has a penicillin allergy and 1%-3% have a cephalosporin allergy: allergies to other beta-lactam antibiotics are very seldom reported.9,12-15 However, skin testing of people who are reported to have a penicillin allergy has shown that 90%-99% do not have a penicillin allergy,9,14 and several authors have concluded that only a small minority of patients who have a self-reported or a documented penicillin allergy are truly allergic to the drug.14,16 This discrepancy can be explained in part by an imprecise definition of the term allergic reaction and also because penicillin sensitivity is lost over time. Approximately 20% of patients who had a confirmed penicillin allergy and had not been exposed to penicillin after the initial identification of the allergy were still allergic 10 years later.9,14

The incidence of allergic reactions caused by antibiotics is miniscule when compared to the number of doses administered and anaphylactic reactions are a very unusual to rare occurrence.9,11 However, it has been estimated that each year 500-1000 people die from anaphylaxis caused by penicillin.9 Hypersensitivity reaction is the most common adverse effect of the cephalosporins,17 and allergic reactions are unpredictable.

Cross-Reactivity

Cephalosporins, penicillins, and the carbapenems are β-lactam antibiotics. The β-lactam antibiotics share a similar structure and patients who have hypersensitivity to one β-lactam antibiotic can be hypersensitive to other drugs in that class or to other, similar nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 12

antibiotics. Someone who is allergic to penicillin could also be allergic to cephalosporins or carbapenems, or someone allergic to cephalexin could be allergic to . This phenomenon is called cross- reactivity.

Cross-reactivity is a well-known and well documented phenomenon but the extent of cross-reactivity is not known.18 Cephalosporin-penicillin cross-reactivity was considered to be relatively common and the cross- reactivity between penicillins and cephalosporins was long thought to be 10%.15,19 However, this figure appears to be too high,16 and Macy (2014) writes: ”There is little, if any, clinically significant immunologic cross-reactivity between penicillins and other beta-lactams.”20 The rate of cross-reactivity between penicillins and cephalosporins is now considered to be as low as 0.6%.21 It typically occurs between penicillins and the first generation cephalosporins. Cross-reactivity between penicillins and the 2nd, 3rd, and 4th generation cephalosporins has been described as negligible;15,22 and the cross-reactivity between penicillins and carbapenems is been reported to be <1%.15

Learning Break: The cross-reactivity between the β-lactam antibiotics appears to be far less than what it was traditionally considered to be and allergy testing and challenge doses may establish the safety of giving a cephalosporin to someone who has a penicillin allergy or vice versa. However, if an antibiotic allergy is documented or if a patient reports that he/she has an antibiotic allergy, the use of drugs from that class of antibiotics or the use of an antibiotic with which there may be cross-reactivity is contraindicated.

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Hepatic Damage

Prescribing information for many antibiotics often instruct clinicians to use these drugs “… with caution in patients with preexisting liver disease or hepatic impairment … Discontinue immediately if symptoms of hepatitis occur (malaise, nausea, vomiting, abdominal colic, fever). Serious liver injury, including irreversible drug induced hepatitis and fulminant hepatic failure (sometimes fatal) have been reported with use.”31-34

Antibiotics are the most common cause of drug-induced liver damage,35,36 and amoxicillin-clavulanate is the most common drug involved in drug-induced liver injury.37-39 (Note: this does not include deliberate overdose of acetaminophen). Approximately 23% of individuals on amoxicillin/clavulanate experience non-significant increases in hepatic enzymes, and the incidence of hepatotoxicity caused by amoxicillin has been estimated to be 1.7 cases per 10,000 prescriptions.39 , ciprofloxacin, , , , nitrofurantoin, , quinolones, sulfamethoxazole-trimethoprim, and can cause liver damage, as well.36,40-43

Risk factors for drug-induced liver damage are not clearly understood and have not been definitively identified. In the majority of cases the damage is temporary and once the offending drug has been discontinued, the liver repairs itself.38

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Learning Break: Antibiotics may not be directly injurious to the liver but the metabolism and clearance of antibiotics may be affected by hepatic impairment, causing drug levels to become elevated and increasing the risk for adverse effects of the drug.

Nephrotoxicity

Drug information resources and prescribing information for almost all of the antibiotics discussed in this learning module state the drugs should be used with caution in patients with renal impairment, antibiotics may cause renal impairment, or that the dosage of the antibiotic should be adjusted according to the patient’s level of kidney function. Some of the cephalosporins, the carbapenems, and the glycopeptides have been implicated as nephrotoxic.44-47

Vancomycin is particularly injurious to the kidneys and Elyasi, et al., (2012) noted that renal toxicity was reported in 10%-20% and 30%- 40%, respectively, of patients who received conventional or high dose treatment with .45

Antibiotic Resistance

Antibiotic resistance occurs when a microorganism survives and multiplies while in the presence of an antibiotic that would usually kill that specific microorganism. Antibiotic resistance is considered to be a nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 15

significant public health problem.23 Microorganisms that are resistant to the available antibiotics have become more common and infections caused by these resistant strains can be quite difficult to treat and have serious implications for the patient and the health care system.24,25

Antibiotic resistance is a long-standing problem. The first penicillin resistant strains of bacteria were noted four years after the drug was mass produced and -resistant was detected within a year of the first clinical use of the drug.26 Antibiotic resistance is a complex phenomenon and there are many contributing factors.

Table 2: Mechanisms of Antibiotic Resistance 23-25,27

Bacterial mutations Inadequate diagnostic capability Inadequate infection control Lack of new antibiotics Non-prescription availability of antibiotics Patient compliance Public hygiene practices Prescribing practices Transmission of resistance

Antibiotic resistance is of particular importance in regard to methicillin- resistant Staphylococcus aureus, often referred to as MRSA, and tuberculosis. Staphyloccocus aureus is a very common microorganism nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 16

that is the cause of many respiratory and skin infections. Methicillin- resistant S. aureus are microorganisms that are resistant to penicillins and other β-lactam antibiotics. Infections with MRSA are a significant public health problem, causing approximately 100,000 new infections and 19,000 deaths per year.28 (Note: The term MRSA is used but methicillin is no longer produced).

Tuberculosis (TB) is still a major health problem in many parts of the world, but fortunately the disease is curable. However, drug-resistant TB, multi-drug resistant TB, and extensively-drug resistant TB are strains of TB that cannot be cured by treatment with the first-line anti- tuberculars or many of the other anti-microbials.29 In fact, the World Health Organization (WHO) estimated that during 2014, 3.3% all new cases of tuberculosis and approximately 20% of all cases of tuberculosis in patients who had been previously treated were caused by a multi-drug resistant strain of tuberculosis mycobacterium.30

Aminoglycosides

The aminoglycosides include , , , and . These drugs are available as intramuscular (IM) and intravenous (IV) solutions, ophthalmic ointments and solutions, oral tablets and solutions, oral inhalation solutions, otic solutions, and topical creams and ointments. is not available in the IM or IV form.

Mechanism of Action

The aminoglycosides inhibit bacterial protein synthesis. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 17

Administration

The patient should be monitored for nephrotoxicity, neurotoxicity, and ototoxicity. Peak and trough levels should be periodically measured, particularly in critically ill patients and patients who are susceptible to the nephrotoxic and ototoxic effect of aminoglycosides. The need for and the timing and frequency of peak and trough drug levels are determined on a case-by-case basis and by the policy of the treating facility. Blood nitrogen and serum creatinine should be measured, intake and output recorded, and audiometric testing should be done before, during, and after therapy with an aminoglycoside. Cross- reactivity between the aminoglycosides may exist.

Adverse Reactions/Warnings

The aminoglycosides are well known for causing nephrotoxicity, ototoxicity, and neuromuscular blockade and paralysis after concomitant use of anesthesia or muscle relaxants, and there are U.S. Boxed Warnings regarding these adverse effects. Neomycin may cause neurotoxic effects such as muscle twitching, numbness, and seizures, especially in patients who have renal impairment or are taking nephrotoxic or ototoxic drugs.

Diarrhea, irritation of the mouth or rectal area, nausea, and vomiting have been reported to occur in 1%-10% of patients taking neomycin. Streptomycin has been associated with arachnoiditis, optic nerve dysfunction, peripheral neuritis, and encephalopathy.

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Nephrotoxicity

Nephrotoxicity is a well-known adverse effect of the aminoglycosides, affecting 5%-25% of patients treated with these drugs.48 Risk factors for aminoglycoside nephrotoxicity include advanced age, dehydration, hepatic dysfunction, hypothyroidism, increasing duration of therapy, metabolic acidosis, pregnancy, renal impairment, and depletion.49

The mode of therapy also influences the risk of nephrotoxicity and current recommendations are to use once daily dosing, also called extended interval therapy; this method has been reported to decrease the incidence of aminoglycoside nephrotoxicity from 17% to 0-5%.49

Ototoxicity

Aminoglycosides can cause damage to the balance and hearing structures of the inner ear. These effects have been reported to occur in approximately 10% of all patients who have been given an IV aminoglycoside and the effects on hearing can be permanent.48,50 Ototoxicity can also occur from the use of aminoglycoside ear drops.51,52 All of the aminoglycosides can affect hearing and balance, but gentamicin and streptomycin are more likely to cause vestibular damage. Amikacin and neomycin predominantly affect hearing and tobramycin affects balance and hearing equally.53,54

Patients who have renal impairment, high drug levels, or are receiving other ototoxic or nephrotoxic drugs are at high risk for aminoglycoside ototoxicity, but balance and hearing disorders can happen to patients nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 19

who have normal renal function and therapeutic drug levels.53 There is evidence that suggests a genetic susceptibility exists for aminoglycoside-induced hearing loss.54,55 Because of the risk of ototoxicity it is recommended that the course of therapy with an aminoglycoside be as short as possible,48,50 and that audiometric testing be done before, during, and after therapy. Hearing loss after aminoglycoside therapy has been stopped has been reported.48,50,55-57

Labeled Uses

Amikacin Amikacin is used as a treatment of serious infections caused by organisms such as Pseudomonas, Proteus, Serratia, and other gram- negative bacilli that are resistant to gentamicin and tobramycin. Examples of these infections include infections, endocarditis, septicemia, and respiratory infections.

Gentamicin Abdominal infections, bone infections, endocarditis, respiratory infections, septicemia, skin and soft tissue infections, and urinary tract infections caused by Pseudomonas, Proteus, Serratia, and gram- positive Staphylococcus.

Neomycin Neomycin is used as an adjunctive therapy for the treatment of hepatic coma and as a surgical prophylaxis.

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Streptomycin Streptomycin is used for the treatment of patients that have tuberculosis, used in conjunction with other anti-tubercular drugs when the primary medications ethambutol, , pyrazinamide, and rifampin cannot be used. Streptomycin is also used to treat infections that cannot be treated with less toxic drugs, infections caused by Brucella, E. faecalis, Enterobacter aerogenes, Enterococcus faecalis in urinary tract infections, Escherichia coli, Francisella tularensis, Haemophilus ducreyi, Klebsiella granulomatis, Klebsiella pneumoniae pneumonia, Proteus spp, and Yersinia pestis.

Chancroid, plague, and gram-negative bacteremia can be treated with streptomycin.

Tobramycin Tobramycin is used for the treatment of documented or suspected infections caused by susceptible gram-negative bacilli, including .

Carbapenems

The carbapenems are β-lactam antibiotics. These drugs, along with the cephalosporins and the penicillins, are called β-lactams because they all have a structure called the β-lactam ring as part of their core.

Imipenem is combined with cilastatin. Cilastatin prevents renal metabolism of . The carbapenems are available as IV solutions. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 21

Table 3: Carbapenem Antibiotics

Doripenem

Ertapenem

Imipenem/Cilastatin

Meropenem

Mechanism of Action

The carbapemens inhibit bacterial synthesis.

Administration

Cross-reactivity with cephalosporins and allergic hypersensitivity is possible, and the use of carbapenems for patients who have had anaphylactic or hypersensitivity reactions to other β-lactam antibiotics is contraindicated. Concomitant use of valproic acid and a carbapenem can lower the blood concentration of valproic acid and cause seizures; this combination should be avoided.58

Adverse Effects/Warnings

The carbapenems have been associated with an increased risk for seizures and thrombocytopenia when they are used for elderly patients and/or patients who have a brain lesion, epilepsy, or impaired renal function.59 The strength of this association is not clearly defined,60 but dose adjustments based on body weight and creatinine clearance are advised when using a carbapenem for these patient populations. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 22

Diarrhea and headache are common side effects of . Prolonged use of carbapemens can cause alteration of the gut microflora and C. difficile-associated diarrhea and pseudomembranous colitis. Decreased hematocrit (18%) and hemoglobin (15%), eosinophilia and thrombocytopenia (13%), and increased serum AST (18%) have been reported in infants and children receiving imipenem.61

The use of a carbapenem is contraindicated if the patient has a history of hypersensitivity to carbapenems or if he/she has had an anaphylactic reaction to a β-lactam antibiotic.

Labeled Uses

Doripenem Doripenem is prescribed to treat patients who have complicated intra- abdominal infections and complicated urinary tract infections caused by susceptible aerobic gram-positive and gram-negative bacteria and anaerobic bacteria

Ertapenem Ertapenem is prescribed to treat patients who have acute pelvic infections including postpartum endomyometritis, septic abortion and post-surgical gynecologic infections, community-acquired pneumonia, and complicated intra-abdominal, skin and skin structure infections, and urinary tract infections. It is also prescribed as a prophylactic drug for prevention of surgical site infections after elective colorectal surgery.

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Imipenem/Cilastatin Iminpenen/Cilastatin is prescribed to treat patients who have bacterial septicemia, bone, joint, skin or skin structure infections, intra- abdominal infections, endocarditis caused by Staphylococcus aureus, gynecologic infections, and lower respiratory tract infections.

Meropenem Meropenem is prescribed to treat bacterial meningitis in pediatric patients 3 months and older if the causative microorganism is Streptococcus pneumoniae, Haemophilus influenzae, or Neisseria meningitides. It is also used to treat complicated skin or skin structure infection and intra-abdominal infections.

Cephalosporins

The cephalosporins are classified as first-generation, second- generation, third-generation, fourth-generation, or fifth-generation. The classification system is based on the effectiveness of each generation against specific microorganisms and the chronological order in which they were developed. For example, the first generation cephalosporins are used for infections caused by certain strains of Streptococci and Staphylococcus aureus and the second-generation cephalosporins are effective against a broader spectrum of bacteria.

Cephalosporins are available as IV solutions and oral capsules, tablets and suspensions.

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Learning Break: Bacteria contain a compound called beta-lactamase that destabilizes the β-lactam ring of β-lactam antibiotics and makes them less effective.

Clavulanic acid is a drug that inhibits the activity of beta-lactamase. These and other beta-lactamase inhibitors are added to antibiotics to increase their effectiveness.

Table 4: Cephalosporins

First-generation: , , and cephalexin

Second-generation: , , , , and

Third-generation: , , cefixime, , , , , and

Fourth generation:

Fifth generation: , ceftolozane and (A cephalosporin combination)

Mechanism of Action

The mechanism of action is the inhibition of the synthesis of a specific part of the bacterial cell wall.

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Administration

Patients should be observed closely for signs and symptoms of hypersensitivity reaction, especially after the first dose. Many drug reference sources advise that renal function should be monitored during therapy with a cephalosporin, and dosing adjustments based on creatinine clearance are recommended for essentially all of the cephalosporins.

Renal injury or impairment is an unusual and rarely reported complication of these medications. However, if the patient has decreased renal function, if he/she is concomitantly receiving a nephrotoxic drug, or if the patient has risk factors for renal impairment or injury such as advanced age or dehydration, then monitoring renal function during therapy with a cephalosporin would be prudent and is recommended.

Cefazolin, cefotetan, ceftriaxone, and ceftolozane/tazobactam contain sodium and this should be considered if the patient has sodium intolerance or congestive heart failure. If the patient has a hypersensitivity to a cephalosporin, administration of any other cephalosporin is contraindicated and caution should be used when administering another β-lactam antibiotic.

Adverse Effects/Warnings

Hypersensitivity reactions, immediate and delayed, are the most common adverse effects of the cephalosporins. Diarrhea, nausea, and vomiting are common, self-limiting side effects of the oral nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 26

cephalosporins. Prolonged use of cephalosporins can cause alteration of the gut microflora and C. difficile-associated diarrhea and pseudomembranous colitis. Many of the cephalosporins cause an increase in the INR laboratory test used to monitor individuals being prescribed warfarin.

Cefotetan and ceftaroline fosamil can cause a positive direct Coombs test. Hemolytic anemia has been reported after administration of cefotetan but not ceftaroline fosamil. If anemia develops during therapy with cefotetan or cetaroline fosamil, drug-induced hemolytic anemia should be part of the differential diagnosis list. Cefpodoxime has been noted to cause diaper rash.

Labeled Uses

There are currently 19 cephalosporins available in the U.S., and a complete discussion of their antimicrobial actions and labeled uses is beyond the scope of this learning module, but the labeled uses are summarized below.

Cefadroxil Pharyngitis and/or tonsillitis, skin and skin structure infections, and urinary tract infection.

Cefazolin Biliary tract infections, bone and joint infections, endocarditis, genital infections, perioperative prophylaxis, respiratory tract infections, septicemia, skin and skin structure infections, and urinary tract infections. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 27

Cephalexin Bone infections, genitourinary infections, otitis media, respiratory tract infections, skin and skin structure infections, and prophylaxis for acute infective endocarditis.

Cefaclor Acute bacterial exacerbations of chronic bronchitis (extended-release tablets only), lower respiratory tract infections (capsules and oral suspension only), otitis media (capsules and oral suspension only), pharyngitis/tonsillitis, secondary bacterial infections of acute bronchitis (extended-release tablets only), and uncomplicated skin and skin structure infections.

Cefotetan Perioperative prophylaxis, intra-abdominal infections and other mixed infections, respiratory tract, skin and skin structure, bone and joint, urinary tract, and gynecologic infections, and septicemia.

Cefoxitin Bone and joint infections, gynecological infections, intra-abdominal infections, lower respiratory tract infections, perioperative prophylaxis, septicemia, skin and skin structure infections, and urinary tract infections.

Cefprozil Pharyngitis or tonsillitis, otitis media, secondary bacterial infection of acute bronchitis and acute bacterial exacerbation of chronic bronchitis, and uncomplicated skin and skin structure infections.

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Cefuroxime Acute bacterial maxillary sinusitis (tablets and oral suspension only), acute otitis media (tablets and oral suspension only), bone and joint infections (injection only), acute bacterial and secondary bacterial bronchitis (tablets only), impetigo, lower respiratory tract infections (injection only), early (tablets only), pharyngitis/tonsillitis (tablets and oral suspension only), septicemia (injection only), uncomplicated skin and skin structure (tablets only), surgical (perioperative) prophylaxis (injection only), and urinary tract infections (tablets and injection only).

Cefdinir Acute bacterial otitis media, acute exacerbations of chronic bronchitis, acute maxillary sinusitis, community-acquired pneumonia, pharyngitis/tonsillitis, and uncomplicated skin and skin structure infections.

Cefditoren Acute bacterial exacerbation of chronic bronchitis or community- acquired pneumonia, pharyngitis/tonsillitis, and uncomplicated skin and skin structure infections.

Cefixime Acute exacerbations of chronic bronchitis, otitis media, pharyngitis/tonsillitis, uncomplicated urinary tract infections, and uncomplicated cervical or urethral gonorrhea.

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Cefotaxime Bacteremia or septicemia, bone or joint infections, CNS infections, genitourinary infections, gynecologic infections, intra-abdominal infections, lower respiratory tract infections, skin and skin structure infections, and surgical prophylaxis.

Cefpodoxime Chronic bronchitis, acute bacterial exacerbation, gonorrhea, otitis media, acute pharyngitis/tonsillitis, community-acquired pneumonia, sinusitis-acute maxillary, uncomplicated skin and skin structure infections, and uncomplicated urinary tract infections.

Ceftazidime Bacterial septicemia, bone and joint infections, CNS infections, empiric therapy in the immunocompromised patient, gynecologic infections, intra-abdominal infections, lower respiratory tract infections, skin and skin structure infections, and urinary tract infections.

Ceftibuten Acute exacerbations of chronic bronchitis, acute bacterial otitis media, and pharyngitis/tonsillitis.

Ceftriaxone Acute bacterial otitis media, bacterial septicemia, bone and joint infections, intra-abdominal infections, lower respiratory tract infections, meningitis, pelvic inflammatory disease, skin and skin structure infections, uncomplicated gonorrhea, urinary tract infections, and surgical prophylaxis. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 30

Cefepime Febrile neutropenia, intra-abdominal infections, moderate to severe pneumonia, skin and skin structure infections, and urinary tract infections, including pyelonephritis.

Ceftaroline fosamil Acute bacterial skin infections and community-acquired bacterial pneumonia.

Ceftolozane and Tazobactam Intra-abdominal infections and urinary tract infections.

Glycopeptides

The glycopeptide antibiotics include , , , and vancomycin. These drugs are available as oral capsules and solutions and IV solutions.

Mechanism of Action

Inhibition of bacterial cell wall synthesis.

Administration

The IV glycopeptides must be administered slowly (30-60 minutes, depending on the drug) and other medications should not be given concurrently through the same IV line. Oritvancin will cause a false elevation of the aPTT (activated partial thromboplastin time) for 48 hours after a dose, and the co-administration of oritavancin and nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 31

warfarin may increase the risk of bleeding. Extravasation of vancomycin can cause tissue irritation and necrosis.

Adverse Effects/Warnings

Rapid IV administration of a glycopeptides antibiotic can cause irritation at the injection site, erythema, pruritus, and urticaria, a phenomenon called the “red man syndrome.”62,63 Dalbavancin has been reported to cause reversible elevations of ALT up to 3 times the upper limit of normal; this laboratory abnormality is reversed once therapy with the drug has been stopped.62 Osteomyelitis was reported to occur during the clinical trials of oritavancin,64 and although the number of patients affected was very small it is recommended that patients be monitored for signs and symptoms of osteomyelitis.65

Prolongation of the QT interval of the heart has been mentioned as an adverse effect of therapy with telavancin.66,67 The significance of this effect is not known but if possible, telavancin should not be given to patients who have heart conditions such as congenital long QT syndrome, prolonged QT interval, left ventricular hypertrophy, uncompensated heart failure, or who are receiving other drugs that can prolong the QT interval.68 As with many other antibiotics, the glycopeptides (vancomycin in particular) can cause nephrotoxicity,44,69 especially in at-risk patient populations. Vancomycin can cause necrosis if there is an extravasation.70

Dosing of these drugs must be adjusted based on creatinine clearance. Periodic measurement of renal function should be done during therapy nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 32

with the glycopeptides and trough levels of vancomycin should be measured in patients deemed to be at risk for kidney damage. Prolonged use of glycopeptides can cause alteration of the gut microflora and C. difficile-associated diarrhea and pseudomembranous colitis.

Labeled Uses

Dalbavancin Treatment of adults who have acute bacterial skin and/or skin structure infections caused by of these gram-positive microorganisms: Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant strains), , Streptococcus agalactiae, and the Streptococcus anginosus group.

Oritavancin Treatment of adults who have an acute bacterial skin and/or skin structure infection caused by one of these gram-positive organisms: Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus group, and Enterococcus faecalis (vancomycin-susceptible isolates only).

Telavancin Treatment of complicated skin and/or skin structure infections caused by methicillin-susceptible or methicillin-resistant Staphylococcus aureus, vancomycin-susceptible Enterococcus faecalis, and Streptococcus pyogenes, Streptococcus agalactiae, or Streptococcus nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 33

anginosus group. Treatment of hospital-acquired and ventilator- acquired bacterial pneumonia.

Vancomycin Vancomycin IV is used to treat patients who have Staphylococcal or Streptococcal infections. Oral vancomycin is used to treat C. difficile- associated diarrhea and enterocolitis caused by Staphylococcus aureus (including methicillin-resistant strains).

Macrolides

The macrolide antibiotics include azithromycin, clarithromycin, erythromycin, fidaxomicin, and telithromycin. The macrolide antibiotics are available as IV solutions, ophthalmic preparations, oral capsules, suspensions, and tablets, and topical preparations

Mechanism of Action

The macrolide antibiotics inhibit bacterial protein synthesis.

Administration

Intravenous azithromycin should be administered slowly over 1 hour. Oral azithromycin extended release should be taken on an empty stomach, 1 hour before or 2 hours after a meal.

Clarithromycin should be dosed every 12 hours to avoid peak and trough levels. Do not give erythromycin with acidic beverages or milk.

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Adverse Effects/Warnings

The macrolide antibiotics can lengthen the QT interval of the heart and cause torsades de pointes.71 The clinical significance of this effect has not been clearly defined,72 and there is evidence that torsades de pointes caused by a macrolide is rare and only occurs if the patient has specific risk factors including but not limited to, advanced age, bradycardia, congestive heart failure, electrolyte abnormalities, female gender, and left ventricular hypertrophy.72 Nonetheless, drug information sources caution that there is substantial evidence that indicates: 1) these drugs can prolong the QT interval and cause torsade de pointes;71 2) clinicians should consider avoiding the use of these drugs in patients who have the aforementioned (and other) risk factors;71 and, 3) prescribers “… should consider the risk of QT prolongation which can be fatal when weighing the risks and benefits of azithromycin for at-risk groups.”73

The macrolide antibiotics have been associated with exacerbating or inducing myasthenia gravis or myasthenic crisis.74,75 Prolonged use of can cause alteration of the gut microflora and C. difficile- associated diarrhea and pseudomembranous colitis.

Labeled Uses

Azithromycin Azithromycin is prescribed for treatment of patients who have acute bacterial exacerbations of chronic obstructive pulmonary disease, acute bacterial sinusitis, community-acquired pneumonia, genital ulcer disease in men, otitis media, Mycobacterium avium complex, pelvic nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 35

inflammatory disease, pharyngitis or tonsillitis, skin and/or skin structure infections, and uretheritis and cervicitis. It is also prescribed for prevention of Mycobacterium avium complex in patients who have advanced human immunodeficiency virus (HIV) infection.

Clarithromycin Infants and children 6 months and older: Acute maxillary sinusitis, acute otitis media, community-acquired pneumonia, disseminated mycobacterial infections, pharyngitis or tonsillitis, and uncomplicated skin/skin structure infections.

Clarithromycin can also be prescribed for prevention of disseminated mycobacterial infections caused by Myobacterium avium complex disease in patients who have an advanced HIV infection and are 20 months or older.

Adults: Acute exacerbation of chronic bronchitis, acute maxillary sinusitis, community-acquired pneumonia, duodenal ulcer disease due to H. pylori (used along with other medications), disseminated mycobacterial infections due to Myobacterium avium or Myobacterium intracellulare, pharyngitis or tonsillitis, and uncomplicated skin/skin structure infections. Clarithromycin can also be prescribed for prevention of disseminated mycobacterial infections caused by Myobacterium avium complex disease in patients who have an advanced HIV infection.

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Erythromycin Erythromycin is used for treatment of susceptible bacterial infections and can be used alone or with neomycin for pre-surgical bowel decontamination.

Fidaxomicin Treatment of Clostridium difficile-associated diarrhea.

Telithromycin Treatment of patients 18 years and older who have mild to moderate cases of community-acquired pneumonia.

Lincosamides

The lincosamide antibiotics include clindamycin and lincomycin. The are available as solutions for IM and IV use and topical preparations - creams, foams, gels, lotions, solutions, suppositories, and swabs.

Mechanism of Action

Inhibition of bacterial protein synthesis.

Adverse Effects/Warnings

Clindamycin systemic and lincomycin: U.S. Boxed Warning – C. difficile-associated diarrhea has been reported and may be mild to severe and possibly fatal; it can cause severe and possibly fatal colitis. It should be reserved for serious infections where less toxic antimicrobial agents are inappropriate, and should not be used in nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 37

patients with nonbacterial infections such as most upper respiratory tract infections.

These drugs should be used with caution in patients who have severe liver disease or renal impairment.

Clindamycin topical - Greater than 10% dermatologic effects such as erythema, exfoliation, irritation, pruritus, and xeroderma; greater than 10% genitourinary effects such as vaginal moniliasis and vulvovaginal pruritus.

Labeled Uses

Clindamycin Bone and joint infections, gynecological infections, intra-abdominal infections, lower respiratory tract infections, septicemia caused by S. aureus, serious infections caused by susceptible strains of streptococci, pneumococci, and staphylococci, and skin and skin structure infections.

Clindamycin Topical Treatment of bacterial vaginosis and severe .

Lincomycin Treatment of serious infections caused by susceptible strains of streptococci, pneumococci, and staphylococci. Lincomycin should only be used for penicillin-allergic patients or other patients for whom penicillin is inappropriate. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 38

Penicillins

The penicillins are perhaps the best known of the antibiotics although they are the second systemic antibiotics to be developed. Penicillin was first used clinically in 1941 and even though the patient did not survive, penicillin was recognized as a major advance in antimicrobial therapy; the drug was effective even when extensively diluted, it was freely diffusible, and it was minimally toxic.76

The penicillins are available as oral tablets, chewable and extended release tablets, oral suspensions, and IM and IV solutions. Of the penicillins, it should be noted that and tazobactam are beta- lactamase inhibitors. Additionally, procaine (a local anesthetic) is used with penicillin G procaine to decrease the pain of IM injection of the drug. The penicillins are listed in the table below.

Table 5: Penicillins

Amoxicillin and Clavulanate Ampicillin Ampicillin and Sulbactam Oxacillin Penicillin G benzathine Penicillin G (Parenteral/Aqueous) Penicillin G procaine Penicillin V potassium Piperacillin and tazobactam nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 39

Mechanism of Action

The penicillins inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins on susceptible bacteria.

Administration

Intravenous infusions of penicillins should be administered slowly; rapid infusion has been associated with seizures. Injection of penicillin G benzathine, penicillin g parenteral/aqueous, and penicillin g procaine intra-arterially, penicillin g procaine IV, or any of these drugs given near a major peripheral nerve can cause severe, permanent neurovascular damage.

Injection of penicillin G benzathine, penicillin g parenteral/aqueous, and penicillin g procaine IM in children <2 years should not be injected in the gluteal area; the mid-lateral muscle of the thigh should be used. Most of the oral penicillins should be taken on an empty stomach, i.e., one hour before a meal or two hours after a meal. Each drug should be checked for specific recommendations.

Adverse Effects/Warnings

All of the penicillins should be used with caution if the patient has renal impairment and as with other antibiotics, prolonged use of penicillin antibiotics can cause C. difficile-associated diarrhea and pseudomembranous colitis. The incidence of gastrointestinal side effects is >10% in patients receiving penicillin V potassium.

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Adverse Effects/Warnings for Specific Penicillins

Renal impairment: Renal function should be measured before and during therapy with amoxicillin-clavulanate, ampicillin, nafcillin, penicillin G parenteral or aqueous, and piperacillin and dosing adjustments made based on creatinine clearance.

Extravasation: Nafcillin is a vessicant, a drug or substance that can cause blistering, and extravasation of nafcillin can cause tissue necrosis.70,77

Liver Damage: The risk of liver damage from amoxicillin-clavulanate has been discussed and amoxicillin-clavulanate is contraindicated if the patient previously had liver damage caused by the drug. Oxacillin has been associated with acute hepatitis and transaminase elevations.78-80

Risk of Seizures: Cloxacillin, penicillin G benzathine, penicillin G parenteral/aqueous, penicillin G procaine, and piperacillin should be used with caution in patients who have a pre-existing seizure disorder and renal impairment as high serum levels of these drugs can increase the risk for seizures.81

The penicllins may also increase the risk of seizures in patients who have a brain lesion or epilepsy.

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Skin Rash: Patients who have cystic fibrosis and receive piperacillin and patients who have mononucleosis and receive ampicillin or piperacillin are likely to develop a skin rash.82-84.

Sodium Content: Nafcillin, oxacillin, penicillin G parenteral or aqueous, and piperacillin have a sodium content that should be considered when these drugs are prescribed for patients who need to restrict their sodium intake.

Thrombocytopenia, anemia, leucopenia, and neutropenia: Hematologic effects have been reported after administration of piperacillin-tazobactam.85-87

Warfarin Drug Interaction: Dicloxacillin and nafcillin may decrease the anti-coagulant effect of warfarin.88,89

Labeled Uses

Amoxicillin-clavulanate Community-acquired pneumonia, otitis media, acute, respiratory tract infections, sinusitis, skin and skin structure infections, and urinary tract infections.

Ampicillin Oral: Genitourinary tract infections, gastrointestinal tract infections, and respiratory tract infections. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 42

Intravenous: Bacterial meningitis, gastrointestinal infections, respiratory tract infections, septicemia and endocarditis, skin and skin structure infections, and urinary tract infections.

Ampicillin-sulbactam Intra-abdominal infections, gynecological infections, and skin and skin structure infections.

Cloxacillin Bone and joint infections, endocarditis, pneumonia, skin and skin structure infections, and sepsis.

Dicloxacillin Osteomyelitis, pneumonia, and skin and soft tissue infections.

Nafcillin Bacteremia, CNS infections caused by susceptible Staphylococcus species, endocarditis, osteomyelitis, and septicemia.

Oxacillin Infections caused by susceptible penicillinase-producing staphylococci.

Penicillin G benzathine Acute glomerulonephritis, respiratory tract infections, prophylaxis for rheumatic fever and chorea, rheumatic heart disease, and syphilis and other venereal diseases.

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Penicillin g parenteral/aqueous Anthrax, botulism, endocarditis, gas gangrene, meningitis, pericarditis, pneumonia, and sepsis.

Penicillin g procaine Anthrax prophylaxis and treatment, diphtheria, endocarditis (subacute), erysipeloid, fusospirochetosis, pneumococcal respiratory infection, rat bite fever, skin and soft tissue infections, streptococcal infections, syphilis, yaws, bejel, and pinta.

Piperacillin Bone and joint infections, intra-abdominal infections, gynecological infections, lower respiratory tract infections, skin and soft tissue infections, urinary tract infections, and infections caused by susceptible streptococci.

Piperacillin-tazobactam Bacterial infections (moderate to severe), community-acquired pneumonia, intra-abdominal infections, nosocomial pneumonia, post- partum endometriosis or pelvic inflammatory disease caused by beta- lactamase-producing strains of E. coli, and skin and skin structure infections.

Sulfonamides

The sulfonamides were introduced in 1936 and they were the first systemic antibiotics. The sulfonamides include sulfadiazine, sulfamethoxazole-trimethoprin, sulfur and sulfacetamide, and

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sulfacetamide topical. These drugs are available as ophthalmic preparations, oral suspensions and tablets, topical cleansers, creams, foams, gels, lotions, pads, suspensions, and washes (sulfur and sulfacetamide), and as IV solutions.

Mechanism of Action

The sulfonamides inhibit folic acid synthesis and this inhibits bacterial growth. Sulfur and the sulfur in sulfacetamide is a keratolytic, a drug that softens and removes the outer layer of the epidermis.

Administration

The oral sulfonamides should be taken with 8 ounces of water and it is recommended that they be administered around the clock to minimize the variations in peak and trough levels. Sulfur and sulfacetamide has not been proven to be effective and/or safe in children <12 years. Sulfur and sulfacetamide is contraindicated if the patient has renal impairment, and dosages of sulfamethoxazole-trimethoprin need to be adjusted to the creatinine clearance level.

Sulfadiazine is contraindicated in infants <2 months unless the baby is being treated for congenital toxoplasmosis.

Sulfacetamide topical can be systemically absorbed if it is applied to abraded, burned, or infected skin.

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Adverse Effects/Warnings

There is “… a clear association between sulfonamides and severe dermatologic reactions.”90 These reactions, specifically Stevens- Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are very uncommon40 but the sulfonamides such as sulfamethoxazole- trimethoprin are among the most common causes of SJS and TEN and these dermatologic adverse effects can cause serious morbidity and death.91-93 Hepatotoxicity is not a common adverse effect of the sulfonamides, but sulfamethoxazole-trimethoprim is one of the top three causes of drug-induced liver injury.36

Stevens-Johnson syndrome and TEN may accompany hepatic injury from sulfamethoxazole-trimethoprim40 and the prescribing information for these drugs states: “Fatalities associated with hepatic necrosis have occurred; discontinue use at first sign of rash or signs of serious adverse reactions.”94-96. Blood dyscrasias such as aplastic anemia agranulocytosis, neutropenia, and thrombocytopenia have been associated with the suflonamides.90,97

Hypoglycemia, , and hyperkalemia have been reported with the use of sulfamethoxazole-trimethoprin in patients who are elderly, have hepatic or renal impairment, are malnourished, or received high doses of the drug.90,98-100

Sulfonamide Allergy

Non-antibiotic sulfonamide drugs such as COX-2 non-steroidal anti- inflammatories, , and sulfonylureas and drugs and food nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 46

products that contain sulfur or sulfites are in common use. There is no cross-reactivity between sulfonamide antibiotics and sulfur or sulfites101 and there is no convincing evidence of cross-reactivity between sulfonamide antibiotics and non-antibiotic sulfonamides.102-107

Because of structural differences and differences in metabolic pathways, prescribing non-antibiotic sulfonamide drugs such as celecoxib, , and glyburide for patients who have a sulfa allergy is unlikely to cause an allergic response. However, it would be prudent to obtain a detailed history of the patient’s allergic response to sulfonamide antibiotics and consider the risk and benefits of using a non-antibiotic sulfonamide drug if the patient has a sulfa allergy.

Labeled Uses

Sulfadiazine Adjunctive treatment in toxoplasmosis with pyrimethamine is FDA approved in ages ≥2 months and adults (it may be used in ages <2 months for treatment of congenital toxoplasmosis). Treatment is generally for chancroid, trachoma, inclusion conjunctivitis, urinary tract infections, and nocardiosis.

Treatment and prophylaxis of meningococcal meningitis, treatment of H. influenza meningitis, prophylaxis of rheumatic fever, prophylaxis in patients who are allergic to penicillin, and treatment of uncomplicated attack of malaria due to chloroquine-resistant Plasmodium falciparum.

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Sulfamethoxazole-trimethoprin Oral: Treatment of urinary tract infections, acute otitis media, and acute exacerbations of chronic bronchitis due to susceptible strains of H. influenzae or S. pneumoniae. Treatment and prophylaxis of Pneumocystis pneumonia, and enteritis.

Intravenously: Treatment of Pneumocystis pneumonia, enteritis caused by Shigella flexneri or Shigella sonnei, and severe or complicated urinary tract infections.

Sulfur and sulfacetamide Treatment of acne vulgaris, acne rosacea, and seborrheic dermatitis

Sulfacetamide topical: Acne (lotion, topical suspension) - Treatment of acne vulgaris. Bacterial infections (cream, wash, lotion and foam) - Treatment of bacterial infections of the skin. Scaling dermatoses (cream, shampoo, wash, lotion and foam) - Treatment of scaling dermatoses such as seborrheic dermatitis and seborrhea sicca (dandruff).

Quinolones

The quinolone antibiotics are available as IV solutions, oral tablets and suspensions, otic drops, and ophthalmic drops and ointments. The ophthalmic and otic preparations will not be discussed in detail.

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Table 6: Quinolone Antibiotics

Ciprofloxacin Gatifloxacin Gemifloxacin Levofloxacin Moxifloxacin Norfloxacin Ofloxacin

Mechanism of Action

The quinolone antibiotics inhibit bacterial DNA recombination, repair, transcription, and transposition.

Administration

The IV quinolones should be infused slowly. Oral quinolones each have specific administration cautions.

Adverse Effects/Warnings

The prescribing information for these drugs notes that hepatotoxicity has been reported from the use of quinolones. Mild and transient elevations of serum aminotransferases are a common side effect of the quinolones108 and hepatic necrosis and toxic hepatitis have been reported after the use of ciprofloxacin.108

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All of the quinolones have been noted to cause hypoglycemia and hyperglycemia.109-112 This effect appears to be dose-related109 and elderly patients and patients who have diabetes or renal failure are most at risk,113,114 but dysglycemia has been reported after use of levofloxacin and moxifloxacin in healthy patients.111,112

A U.S. boxed warning is included in the prescribing information for all of the quinolones regarding the use of these drugs in patients who have myasthenia gravis, and states: “May exacerbate muscle weakness related to myasthenia gravis. Cases of severe exacerbations, including the need for ventilatory support and deaths have been reported; avoid use in patients with myasthenia gravis.” This warning is supported by case reports.115,116

Prolongation of the QT interval of the heart is a documented side effect of the quinolones117 and prescribing information warns that these drugs “… may prolong QT interval; avoid use in patients with a history of QT prolongation, uncorrected hypokalemia, hypomagnesemia, or concurrent administration of other medications known to prolong the QT interval…”114 QT prolongation is a recognized risk factor for torsades de pointes (TDP) and the concern is that QT prolongation caused by the quinolones can initiate this deadly arrhythmia.

Drug information sources note that drugs such as levofloxacin “… prolong the QT interval and are associated with the risk of TDP, even when taken as directed in official labeling.”71 However, the risk for TDP caused by a quinolone appears to be very low,117 and TDP caused by a quinolone and preceded by QT prolongation is far more likely to occur nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 50

if other risk factors are present, including but not limited to, advanced age, bradycardia, cardiovascular disease, congestive heart failure, female gender, electrolyte abnormalities, and left ventricular hypertrophy.

Tendinitis and/or tendon rupture, most often in the Achilles tendon, has been associated with the use of quinolones118-120 and the FDA requires a Boxed Warning regarding this injury to be included in prescribing information for these drugs.118 The estimated occurrence of tendinitis and tendon rupture caused by the quinolones is 0.14%- 4%.118

Ciprofloxacin Avoid administering ciprofloxacin with . Give immediate release ciprofloxacin and extended release Cipro at least 2 hours before or 6 hours after antacids or products containing , iron, or zinc. The oral suspension should not be given through a feeding tube. If immediate release tablets are given through a feeding tube, the feeding tube should be flushed before and after administration. Tube feedings should be held at least 1 hour before and 2 hours after administration. Good hydration should be maintained.

Gemifloxacin Gemifloxacin may be given with or without food, milk, or calcium supplements. Gemifloxacin should be taken 3 hours before or 2 hours after supplements and/or multivitamins containing iron, , or zinc. Good hydration should be maintained.

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Levofloxacin The oral solution should be administered on an empty stomach, 1 hour before or 2 hours after a meal. Oral levofloxacin should be taken 2 hours before or 2 hours after multivitamins, antacids, or other products containing aluminum, iron, magnesium, or zinc. Good hydration should be maintained.

Moxifloxacin Moxifloxacin can be taken with or without food, but it should be taken 4 hours before or 8 hours after multivitamins, antacids, or other products containing aluminum, iron, magnesium, or zinc. Good hydration should be maintained.

Norfloxacin Antacids, sucralfate, and multivitamins or other products containing aluminum, iron, magnesium, or zinc should not be given with 2 hours of an oral dose of norfloxacin. Norfloxacin should be taken 1 hour before or 2 hours after a meal or dairy products.

Ofloxacin Should not be taken within 2 hours of food or any antacids, which contain aluminum, magnesium, or zinc.

Labeled Uses

Ciprofloxacin Children: Complicated urinary tract infections and pyelonephritis due to E. coli. Although effective, ciprofloxacin is not the drug of first choice in children. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 52

Children and Adults: To reduce incidence or progression of disease following exposure to aerosolized Bacillus anthracis; prophylaxis and treatment of plague, including pneumonic and septicemic plague, due to Yersinia pestis.

Adults: Treatment of the following infections when caused by susceptible bacteria: urinary tract infections; acute uncomplicated cystitis in females and chronic bacterial prostatitis; lower respiratory tract infections (including acute exacerbations of chronic bronchitis); acute sinusitis, skin and skin structure infections, bone and joint infections, complicated intra-abdominal infections (in combination with metronidazole), infectious diarrhea, typhoid fever due to Salmonella typhi (eradication of chronic typhoid carrier state has not been proven), uncomplicated cervical and urethra gonorrhea (due to N. gonorrhoeae), nosocomial pneumonia, and as empirical therapy for febrile neutropenic patients (in combination with piperacillin).

Gatifloxacin

Treatment of bacterial conjunctivitis

Gemifloxacin Treatment of acute exacerbation of chronic bronchitis and community- acquired pneumonia, including pneumonia caused by multidrug- resistant strains of S. pneumoniae.

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Levofloxacin Treatment of community-acquired pneumonia, including multidrug resistant strains of S. pneumoniae, nosocomial pneumonia, chronic bronchitis (acute bacterial exacerbation), acute bacterial rhinosinusitis, prostatitis, urinary tract infection (uncomplicated or complicated), acute pyelonephritis, skin or skin structure infections (uncomplicated or complicated), to reduce incidence or disease progression of inhalational anthrax (post-exposure), for prophylaxis and treatment of plague (pneumonic and septicemic) due to Y. pestis. Levofloxacin ophthalmic is used to treat bacterial conjunctivitis.

Moxifloxacin Treatment of mild to moderate community-acquired pneumonia, including multidrug-resistant Streptococcus pneumoniae, acute bacterial exacerbation of chronic bronchitis, acute bacterial sinusitis, complicated and uncomplicated skin and skin structure infections, complicated intra-abdominal infections, prophylaxis and treatment of plague (pneumonic and septicemic plague) due to Yersinia pestis. Moxifloxacin ophthalmic is used to treat bacterial conjunctivitis.

Norfloxacin Treatment of uncomplicated and complicated urinary tract infections caused by susceptible gram-negative and gram-positive bacteria, sexually-transmitted diseases caused by N. gonorrhoeae, and prostatitis due to E. coli.

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Ofloxacin Treatment of acute exacerbations of chronic bronchitis, community- acquired pneumonia, skin and skin structure infections (uncomplicated), urethral and cervical gonorrhea (acute, uncomplicated), urethritis and cervicitis (nongonococcal), mixed infections of the urethra and cervix, pelvic inflammatory disease (acute), cystitis (uncomplicated), urinary tract infections (complicated), and prostatitis. Ofloxacin ophthalmic is used to treat conjunctival and/or corneal bacterial infections. Ofloxacin otic is used to treat acute otitis media externa, chronic suppurative otitis media, and otitis externa.

Tetracyclines

The tetracycline antibiotics include demeclocycline, , minocycline, and tetracycline. The are available as oral capsules, solutions, suspensions, and tablets and as solutions that can be given IV.

Mechanism of Action

The tetracyclines inhibit bacterial cell wall synthesis.

Administration

Tetracyclines should not be taken with antacids, calcium supplements, or multivitamins as these will decrease the absorption of the tetracyclines. The oral tetracyclines should be taken with at least 8 ounces of water and the patient should remain upright for 30 minutes nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 55

after administration in order to avoid esophageal irritation. Minocycline may be taken with food; the other tetracyclines should be taken 1-2 hours after a meal.

Adverse Effects/Warnings

Tetracyclines should be used cautiously and dose adjustments should be made if the patient has renal impairment. Tetracyclines are classified as an FDA pregnancy risk category D drug: there is positive evidence of risk to the fetus and these drugs should not be used during pregnancy unless the benefit outweighs the risk.

Hyperpigmentation and discoloration of the teeth and disruption of enamel formation are a well-documented and very common (up to 92% in some studies) adverse effect of tetracycline that can occur if tetracycline is given when teeth are developing;121,122 use of these drugs should be avoided in children <8 years of age. The level of risk for this adverse effect after administration of the other tetracyclines is not known.121

Photosensitivity is a common adverse effect caused by tetracyclines.123-125 It is usually manifested by erythema similar in appearance to sunburn and discontinuation of the drug is typically the only treatment that is needed.125 Prolonged use may cause C. difficile- associated diarrhea or pseudomembranous colitis. is a common adverse effect of demeclocycline.126,127

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Increased intracranial pressure has been commonly reported as an adverse effect of the tetracyclines.128,129 This will usually resolve after the drug has been discontinued. Serious sequelae from increased intracranial pressure are rare and more common in obese females of childbearing age and/or who have a history of intracranial hypertension.130

Labeled Uses

Demeclocycline Treatment of urinary tract and respiratory tract infections caused by susceptible bacteria. This drug is not often prescribed; the other tetracyclines are preferred.

Doxycycline Treatment of patients infected by susceptible Rickettsia, Chlamydia, Chlamydophila, and Mycoplasma. It is used as a malaria prophylaxis. It is prescribed to treat patients who have anthrax infection, Clostridium infection if the patient is allergic to penicillin, community- acquired pneumonia, gonorrhea and syphilis, and infections with uncommon organisms such as Bartonella bacilliformis, Borrelia recurrentis, Brucella spp, Campylobacter fetus, Francisella tularensis, Haemophilus ducreyi, Klebsiella granulomatis, Ureaplasma urealyticum, Vibrio cholerae, and Yersinia pestis (plague).

Doxycyline can also be used to treat severe acne, intestinal amebiasis, and Q fever.

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Minocycline Treatment of acne, actinomycosis, anthrax, and asymptomatic carriers of Neisseria meningitides. Treatment of Campylobacter fetus infections, cholera, Clostridium spp infections, gram-negative infections, listeriosis, meningitis, ophthalmic infections, relapsing fever, respiratory tract infections, rickettsial infections, sexually transmitted infections, skin and skin structure infections, urinary tract infections, Vincent infection, yaws, and zoonotic infections.

Tetracycline Treatment of infections caused by Chlamydia, Mycoplasma, and Rickettsia. Treatment of bacterial infections caused by susceptible gram-negative and gram-positive bacteria. Tetracycline can also be used to treat patients who have acne, exacerbations of chronic bronchitis, sexually transmitted diseases if the patient is allergic to penicillin, and patients who have tularemia. Tetracycline is used with other drugs to eradicate H pylori.

Miscellaneous Antibiotics: Metronidazole And Nitrofurantoin

Metronidazole

Mechanism of Action

Metronidazole inhibits bacterial protein synthesis by disrupting DNA structure.

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Administration

Extended release metronidazole tablets should be taken 1 hour before or 2 hours after a meal. Patients taking metronidazole should avoid drinking during therapy and for 3 days after the last dose.

Concomitant use of ethanol and metronidazole has been reported to cause a disulfiram-like reaction. Disulfiram, commonly known by the trade name Antabuse, interferes with the metabolism of ethanol by inhibiting the activity of acetaldehyde dehydrogenase and the accumulation of acetaldehyde causes diaphoresis, headache, facial flushing, nausea, palpitation, and vomiting. These effects explain why Antabuse is used as a treatment for an alcohol use disorder.

Metronidazole is thought to have a similar inhibitory effect on acetaldehyde dehydrogenase and there have been case reports documenting a disulfiram-like reaction when ethanol and metronidazole are taken together, but there is some doubt that there is a true-cause and effect relationship.131,132 Metronidazole is available as oral capsules, regular and extended release, and as an IV solution.

Adverse Reactions/Warnings

U.S. Boxed Warning: Possibly carcinogenic based on animal data. Headache, nausea, and vaginitis are common adverse effects of metronidazole.

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Labeled Uses

Amebiasis, anaerobic bacterial infections (caused by Bacteroides spp, including the B. fragilis group), bacterial septicemia, bacterial vaginosis, bone and joint infections, CNS Infections including meningitis and brain abscess, endocarditis, intra-abdominal infections, lower respiratory tract infections, skin and skin structure infections, surgical prophylaxis for colorectal surgery, and trichomoniasis.

Nitrofurantoin

Mechanism of Action Nitrofurantoin inhibits bacterial protein and cell wall synthesis, disrupts bacterial DNA and RNA activity, and inhibits aerobic metabolism.

Administration Nitrofurantoin should be taken with meals.

Adverse Effects/Warnings Nitrofurantoin is contraindicated if the patient’s creatinine clearance is <60 mL/min. Nitrofurantoin is contraindicated in pregnant patients who are between 38-42 weeks gestation and during labor and delivery, and it is contraindicated in neonates <1 month. In all of these circumstances immature erythrocytes may be at risk for hemolysis, and the drug should be used with caution in patients who are G6PD (an enzyme known to protect red blood cells) deficient.

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Labeled Uses

Acute cystitis in patients ≥12 years and treatment of urinary tract infections.

Guideline For Administering Antibiotics

Safely administering antibiotics requires knowing the risks and hazards that are common to all antibiotics and the specific risks and hazards of each drug. Of course, given the number and complexity of reported adverse effects and cautions for all the antibiotics and for the specific drugs this can seem to be an impossible task but it is actually a simple process. The risks and hazards common to antibiotics are summarized below, and information about the risks and hazards particular to each antibiotic is widely available.

Risks and Hazards of Antibiotics

Allergic Reactions All of the antibiotics can cause allergic reactions and cross-reactivity between antibiotics of the same class and antibiotics of different classes can occur. However, the β-lactam antibiotics are far more likely to cause an allergic reaction than other antibiotics and even with those drugs the risk is not high and cross-reactivity between antibiotics is unusual.

Allergic reactions cannot be totally prevented. However, using the following approach can diminish the risk of their occurrence and any potential harm:

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1. Always ask the patient if he/she is allergic to any antibiotics and/or checking the record for documentation of an antibiotic allergy, which should be done before giving the patient a first dose.

2. Reading the prescribing information.

3. Knowing the names of the classes of antibiotics. If the prescribing information notes that an antibiotic is contraindicated if the patient is allergic to other cephalosporins or carbapenems, this information would be of no value if the clinician did not know what those terms meant.

4. Realizing that allergic reactions can range from mild to life threatening and that they can be immediate and delayed. Many people assume that allergic reactions happen immediately but this is not true.

5. Knowing that cross-reactivity can occur between classes of antibiotics.

Gastrointestinal Adverse Effect Mild and temporary gastrointestinal problems such as nausea and diarrhea are common side effects of all oral antibiotics, but serious C. difficile infections caused by alteration of the gut micro-flora are possible and these infections cause diarrhea, as well. Serious antibiotic associated diarrhea should be suspected if:

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1. the onset occurs while the patient is hospitalized; 2. the patient is elderly and/or has a compromised immune system or is receiving a proton pump inhibitor; 3. the patient has a fever and/or has frequent, copious, watery stools; and, 4. the patient has had C. difficile-associate diarrhea before; remember that C. difficile-associated diarrhea can begin weeks after the last dose of an antibiotic.

Hepatic Adverse Effects The prescribing information for essentially every antibiotic notes that caution should be used in patients with preexisting liver disease or hepatic impairment and that serious liver injury, including irreversible drug-induced hepatitis and fulminant hepatic failure (sometimes fatal), have been reported with use. However, although drug-induced liver damage is relatively common to some of the antibiotics, serious hepatic damage is not.

Safe administration of antibiotics in terms of hepatic injury and/or impairment requires the clinician to: 1) observe the patient for signs and symptoms of liver damage; and, 2) be aware that if the patient has pre-existing liver impairment the metabolism of the antibiotic may be decreased, increasing blood levels and the risk for antibiotic adverse effects.

Nephrotoxicity It’s important for the clinician to be aware that: 1) nephrotoxicity is a possible adverse effect of antibiotics and that impaired renal function nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 63

can decrease of antibiotics; 2) some of the cephalosporins, the carbapenems, and the glycopeptides are especially likely to cause kidney damage; 3) patients at risk for nephrotoxicity must be identified, i.e., the elderly, and patients who are dehydrated, febrile, and have renal impairment; and, 4) it’s important to monitor the patient’s intake and output, BUN, creatinine and, if indicated, the peak and trough levels of the drug.

Administration There are exceptions but most IV doses of antibiotics should be administered slowly; rapid infusion can cause seizures. Some of the IV antibiotics have sodium as part of their formula, an obvious hazard for certain patients. Finally, many of the oral antibiotics have specific requirements in terms of co-administration with food, antacids, or other medications.

If clinicians are unfamiliar with an antibiotic, they should check the prescribing information before giving it to see what if any dietary restrictions apply.

Pregnancy The FDA has 5 categories of risk that can be assigned to a drug to indicate its potential for harm to a fetus. This is outlined in the table below.

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Table 7: Pregnancy Risk Categories

Category A: Adequate, well-controlled studies have failed to demonstrate a risk to the fetus during the first trimester of pregnancy, and there is no evidence of risk in later trimesters.

Category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

Category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Category X: Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.

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Table 8: Category B Antibiotics

Cephalosporins Doripenem Ertapenem Meropenem Vancomycin (Oral) Azithromycin Erythromycin Fidaxomicin Telitromycin

Clindamycin Pencillins Metronidazole Nitrofurantoin

Table 9: Category C Antibiotics

Aminoglycosides Imipenem Dalbavancin Oritavancin Telavancin Vancomycin (IV) Clarithromycin Lincomycin Sulfaziadine Sulfur-sulfaziadine Sulfacetamide (Topical) Quinolones

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Patient Teaching

Patient teaching is essential for the safe and effective use of antibiotics. The effectiveness of these drugs can be diminished by poor patient compliance and improper use. The following points should be discussed with the patient and his/her understanding of them evaluated.  What is this medicine for?  Are there any restrictions with this drug? For example, could this make me drowsy so I should not drive after taking the drug?  When should I take the medicine?  Should I take the medicine with food or on an empty stomach?  If the medication must be taken on an empty stomach, how long before and after a meal should it be taken?  What are the common side effects with this medicine? If I am having a side effect when should I call the prescriber?  Are there any necessary follow-ups either by exam or laboratory evaluation for monitoring this medicine?  Can this medicine interact with any of my other medicines?  Are there over-the-counter drugs or foods I should avoid while I am taking this medication?  Are there any severe risks with this medicine?  What should I do if I miss a dose of the medicine?  Can I drink alcohol while taking this medicine?

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Summary

Common antibiotics used in the United States, specifically the aminoglycoside, carbapenem, cephalosporin, glycopeptide, lincosamide, macrolide, penicillin, quinolone, sulfonamide, and tetracycline antibiotics, and metronidazole and nitrofurantoin, have been reviewed primarily in terms of drug indication, administration and adverse effects/warnings. Additionally, labeled use of various antibiotic drug classes and use of specific drugs have been summarized in terms of their antimicrobial actions. Specific patient populations and risk factors were raised as important considerations to ensure the appropriate use of a drug.

Importantly, clinicians are reminded that antibiotic resistance has become a long-standing problem. Patient history taking and education are essential before starting antibiotic treatment to optimize efficacy of the drug to kill an offending organism and to avoid the development of a resistant strain. Microorganisms that are resistant to the available antibiotics have become more common and infections caused by these resistant strains can be quite difficult to treat and have serious implications for the patient and the health care system.

Please take time to help NurseCe4Less.com course planners evaluate the nursing knowledge needs met by completing the self-assessment of Knowledge Questions after reading the article, and providing feedback in the online course evaluation.

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1. Antibiotic-associated diarrhea a. can have a delayed onset and cause serious complications. b. occurs after the first dose and is always mild and self-limiting. c. only occurs in women > age 60. d. typically affects hospitalized neonates.

2. Allergic reactions to antibiotics a. always happen within one hour after a dose. b. can be delayed in onset. c. are always severe and life-threatening. d. only occur in people who have a compromised immune system.

3. True or false: Someone who is allergic to penicillin may be allergic to cephalosporins. a. True b. False.

4. Patients who are receiving antibiotic therapy should be monitored for a. osteoporosis. b. polycythemia. c. diabetes mellitus. d. nephrotoxicity.

5. Which of these antibiotics is well known for causing ototoxicity? a. Carbapenems. b. Metronidazole. c. Aminoglycosides. d. Quinolones. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 69

6. Therapy with quinolone antibiotics can place the patient at risk for a. QTc prolongation b. hemolytic anemia. c. ototoxicity. d. tendon rupture.

7. Which of the following is a Boxed Warning for Levofloxacin? a. Hemolytic anemia. b. Tendon rupture. c. Seizures. d. Ototoxicity.

8. Which of the following is well-documented adverse effect of the tetracyclines? a. Tendon rupture. b. Ototoxicity. c. Teeth staining. d. Torsades de Pointes.

9. A patient who is allergic to a sulfonamide antibiotic a. should never take a food or drug that contains sulfites. b. should never take a non-antibiotic sulfonamide. c. will be allergic to the cephalosporins. d. may be allowed to take a non-antibiotic sulfonamide.

10. True or false: Patients taking metronidazole can safely drink alcohol. a. True. b. False. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 70

11. Clostridium-difficile-associated diarrhea a. is a major risk of antibiotic use. b. is primarily a nosocomial infection. c. may cause death and sepsis. d. All of the above.

12. Vancomycin IV is used to treat patients who have a. Staphylococcal or Streptococcal infections. b. C. difficile-associated diarrhea. c. enterocolitis. d. necrosis.

13. Rapid IV administration of a glycopeptides antibiotic can cause skin rashes and irritation known as a. Torsade de Pointes. b. nosocomial infection. c. “red man syndrome.” d. Stevens-Johnson syndrome.

14. Anaphylaxis, an allergic reaction caused by antibiotics, i.e., penicillins, is more likely caused by a. topical administration. b. oral administration. c. parenteral administration. d. administration by gastric feeding tube.

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15. Patients administered oritavancin should be monitored for signs and symptoms of a. Stevens-Johnson syndrome. b. osteomyelitis. c. enterocolitis. d. tendon rupture.

16. Extravasation of ______can cause tissue necrosis. a. nafcillin b. vancomycin. c. sulfacetamide topical. d. answers a and b.

17. Which antibiotics have a higher risk of increasing seizures in patients? a. Penicllins b. Glycopeptides c. Valproic acid d. Tetracyclines

18. Sulfamethoxazole-trimethoprim is one of the top three causes of drug-induced a. ototoxicity. b. seizures. c. severe colitis. d. liver injury.

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19. Tetracyclines should not be taken with antacids, calcium supplements, or multivitamins as these will a. increase the risk of osteomyelitis. b. increase the risk of bleeding. c. always cause nausea. d. decrease the absorption of the tetracyclines.

20. True or false: Antibiotics are the most common cause of drug- induced liver damage. a. True. b. False.

Correct Answers:

1. A 11. D 2. B 12. A 3. A 13. C 4. D 14. C 5. C 15. B 6. A 16. D 7. B 17. A 8. C 18. D 9. D 19. D 10. B 20. A

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References Section

The reference section of in-text citations include published works intended as helpful material for further reading. Unpublished works and personal communications are not included in this section, although may appear within the study text.

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