WHO Drug Information Vol. 7, No. 2, 1993 Essential Drugs Guidelines for antimicrobial countries if the resistance of important bacterial pathogens is to be monitored. In response to this susceptibility testing need, the WHONET (2, 3) programme was (intermediate laboratories) developed by the WHO Collaborating Centre for Surveillance of Antimicrobial Resistance. lt is now operating in some 100 hospitals, mostly in the Introduction United States, and it is expanding in South America and the western Pacific region. The system will not Although many communicable diseases have been be fully effective, however, until every country has a effectively contained, bacterial infections remain a national reference laboratory that is actively major cause of morbidity and mortality particularly reporting to this network. in developing countries. lt has been stressed repeatedly that the increas­ The concept of "reserve antimicrobials" was ing prevalence of strains of common pathogenic introduced to WHO's Model List of Essential Drugs bac-teria resistant to widely-available, relatively­ in 1989 (4). This resulted from increasing concern cheap antimicrobials such as those included in about the emergence of important pathogens that WHO's Model List of Essential Drugs (1) is have developed resistance to all "essential" dangerously eroding their effectiveness not only for antimicrobials. A reserve antimicrobial was defined the treatment of individual patients but also for the as "an antimicrobial which is useful for a wide range community at large. of infections but, because of the need to reduce the risk of development of resistance and because of Whenever one such drug or class of drugs is its relatively high cost, it would be inappropriate to used excessively, genetic changes favouring the recommend its unrestricted use". This concept emer-gence of antimicrobial-resistant bacteria becomes tangible, however, only when means exist tend to supervene. Although this can occur after of demonstrating prevailing sensitivity patterns. This only a single exposure in an individual patient, it implies a need for precise laboratory investigation. usually emerges after a sustained period of use. Without these facilities seriously-ill patients are Resistance is generally stable and passed on for endangered. several generations of bacteria. The spread of anti­ microbial-resistant clones of bacteria within a host If antimicrobial resistance is to be controlled, sev­ population or environment is also important. This is eral independent measures need to be undertaken: most noticeable in hospitals where certain resistant organisms can become endemic and may infect 1. Routine surveillance of antimicrobial-resistant many patients. The danger is intensified by poor bacteria using standardized, predictive test hygienic practices in the hospital and/or lack of methods must be introduced in hospital and adequate training in control and containment of community settings. nosocomial and other infections. The spread of resistant bacteria within the community is of even 2. Antimicrobial prescribing guidelines must be greater importance. This seriously compromises developed that will assure effective treatment and presumptive initial therapy of common bacterial not encourage the emergence and spread of infections and requires revision of routine anti­ antimicrobial-resistant bacteria. microbial strategies. 3. Comprehensive national programmes must be The need for more systematic and coordinated implemented that respect standards of good international approaches to laboratory monitoring of laboratory practice, with the objective of assuring antimicrobial sensitivity has become important and quality and availability of antimicrobials. urgent. Microbiological laboratories including national reference laboratories need to be 4. Adequate training of technical personnel must be established in developing as well as developed assured. 68 WHO Drug lnfonnation Vol. 7, No. 2, 1993 Essential Drugs 5. Systems must be developed within the context of 1. Community-acquired infections WHONET whereby each country can collate and disseminate information on antimicrobial resistance These infections are caused by organisms highly to hospitals and health workers. prevalent in the community. Some can be treated on an outpatient basis and others are severe The following guidelines concern routine surveil­ enough to require hospital admission for diagnosis lance of antimicrobial-resistant bacteria using tests and therapy. which can be undertaken in intermediate level laboratories. Causative Drugs used as markers Susceptibility testing organisms of antimicrobial resistance Since the majority of infections which arise in man are not investigated by microbiological methods, Staphylococcus aureus benzylpenicillin, oxacillin antimicrobial treatment is usually administered on erythromycin, gentamicin the basis of a presumptive etiological diagnosis determined by the clinical history and findings. Streptococcus benzylpenicillin as predicted Microbiological investigations are carried out where pneumoniae by the oxacillin disc test the etiology is uncertain, in severe infections when erythromycin patients fail to respond to empiric therapy or chloramphenicol, sulfamethoxazole develop a new infection during the course of trimethoprim therapy, or for public health purposes. Additionally, in vitro susceptibility tests are performed when an Streptococcus (benzylpenicillin)2 organism is known to have unpredictable sensitivity. pyogenes erythromycin Susceptibility tests are carried out on anti microbials Haemophilus ampicillin, chloramphenicol to which the organism is normally susceptible in influenzae sulfamethoxazole, trimethoprim order to determine whether resistance has by estimating beta­ emerged. Demonstration of a prevalence of lactamase production resistant strains could influence recommendations for presumptive antimicrobial therapy. Neisseria benzylpenicillin, tetracycline 1 1 2 gonorrhoeae (ciprofloxacin , ceftriaxone ) Clinically and epidemiologically by estimating beta­ important bacteria and essential lactamase production antimicrobials for susceptibility testing Escherichia coli ampicillin, sulfamethoxazole (UTI) trimethoprim, nitrofurantoin General principles nalidixic acid, sulfonamide (gentamicin)>2 i) The antimicrobial substances listed in these (fluoroquinolone)2- (cefalosporin)32 guidelines are commonly used in presumptive therapy. This list is illustrative rather than Salmonella typhi and ampicillin comprehensive; other drugs may be important in other invasive chloramphenicol various countries or regions. Salmonella sulfamethoxazole, trimethoprim 2 2 ii) Some of the drugs listed are index compounds (fluoroquinolone) , (cefotaxime) representative of a defined group of drugs, e.g.; oxacillin resistance in staphylococci indicates Shigella spp. ampicillin, sulfamethoxazole resistance to other beta-lactams. trimethoprim, tetracycline 2 (chloramphenicol) , nalidixic acid' iii) The most important types of resistance are easy (fluoroquinolone )2 to detect in rapidly-growing organisms. In contrast, detection of resistance in fastidious and anaerobic Vibrio cholerae tetracyclines, sulfamethoxazole bacteria requires a high degree of technical trimethoprim, nitrofurantoin 2 expertise. In such circumstances, testing should be (erythromycin) , (chloramphenicol)2 carried out in central reference laboratories, wherever possible. 69 Essential Drugs WHO Drug Information Vol. 7, No. 2, 1993 2. Hospital-acquired infections 3. Central reference laboratories usually located in the capital city or in a university hospital. These infections arise in patients who are either in Facilities for bacteriological culture and suscepti­ hospital or who have recently been discharged from bility testing are generally not available at the hospital. The causative organism is derived either peripheral level. Laboratory support in microbiology from the patient's endogenous flora or from the will be limited to microscopy and to some simple flora which are endemic in the hospital. and rapid tests for the detection of antibodies (typhoid, syphilis) or antigens (meningitis, Causative Drugs used as markers Chlamydia). organisms of antimicrobial resistance Most intermediate laboratories should have the facilities to culture, identify and establish the Staphylococcus aureus benzylpenicillin susceptibility of common pathogens such as erythromycin, oxacillin Shigella, Salmonella spp., Vibrio cholerae, gentamicin, (vancomycin? staphylococci, nosocomial Gram-negative bacilli, streptococci, meningococci, gonococci, pneumo­ Coagulase-negative benzylpenicillin cocci and Haemophilus influenzae. Susceptibility staphylococci erythromycin, oxacillin testing should also be routinely performed at least gentamicin, (vancomycin? for rapidly-growing pathogens. For fastidious bacteria, testing may be limited to rapid, inexpen­ Enterococci ampicillin, gentamicin sive methods notably beta-lactamase testing of (vancomycin)2 Haemophilus and gonococci and elementary or disc-test screening, using for instance oxacillin as a Pathogenic Gram-negative ampicillin marker for penicillin resistance in pneumococci. bacilli epidemic or endemic chloramphenicol in hospitals sulfamethoxazole All isolates of Shigella, Salmonella and Vibrio spp. including E. coli, trimethoprim and representative isolates of pneumococci, Klebsiella spp., gentamicin, (fluoroquinolone)2 H. influenzae, meningococci and gonococci should 3 Salmonella, (cefalosporin ) be forwarded to a central