Selection of antimicrobial agents for antimicrobial resistance surveillance programmes

The selection of antimicrobial agents to include in a programme for surveillance of resistance is not fundamentally different from the choice of drugs for sensitivity tests in the clinical laboratory. The selection of the most appropriate antibiotics to test is an important decision that should be made by the head of the laboratory after consultation with the medical staff. As a general principle, only those antibiotics that are of potential use in treating infections caused by the given organism should be included and reported. However, in surveillance studies it may be useful to include an antibiotic for purely epidemiological reasons. The inclusion of irrelevant antibiotics not only constitutes a waste of time and materials, but it may confuse or misguide the clinician and lead to inappropriate treatment. With most groups of organisms six or seven antibiotics will be sufficient for routine reporting. Supplemental agents should be added in special circumstances (multiresistant organisms, severe infections).

The choice of agent will differ from country to country and from laboratory to laboratory, depending on national or local preferences or availability. Some general rules should guide the choice of antibiotics in the sensitivity test and apply equally to clinical use as to epidemiological surveillance.

Only those antibiotics should be tested that are of proven clinical efficacy for the corresponding group of organisms. Priority should be given to the antibiotics contained in the WHO Model List of Essential Drugs and more particularly to those recommended in the WHO special programmes for acute respiratory infections, diarrhoeal diseases and sexually transmissible diseases. The choice should be in conformity with local hospital formularies and with national or international guidelines for antimicrobial therapy.

Antibiotics which are universally active or inactive against a given group of organisms need not be tested, e.g. penicillin G for group A streptococci, macrolides for Gram-negative enteric rods.

Antimicrobials which are only used for the treatment of urinary tract infections should just be tested against isolates of the urinary tract, e.g. sulfonamides, nitrofurantoin, nalidixic acid, norfloxacin. The latter two, however, may also be included in the test panel for enteric pathogens, e.g. Shigella.

Some antibiotics form groups or families with rather similar or identical in vitro activities and a high degree of cross-resistance. As a rule only one representative of such a group should be tested and the result extrapolated to the entire group.

Penicillin G is representative of all penicillinase-sensitive penicillins when testing staphylococci.

Oxacillin or methicillin is representative not only of all penicillinase-resistant penicillins but resistance extends also to all other b-lactams including the cephalosporins and combinations with b-lactamase inhibitors such as amoxycillin-clavulanic acid (augmentin). Oxacillin is preferred in the disc test for its stability and the more reliable detection of methicillin-resistant Staphylococcus aureus (MRSA). The rule is also valid for coagulase-negative staphylococci.

Ampicillin is representative of amoxycillin and ampicillin esters.

Tetracycline is representative of all tetracyclines (although minocycline has a wider in vitro spectrum).

Erythromycin is the only macrolide which should be tested.

Clindamycin is representative of lincomycin.

Only one sulfonamide should be tested.

The cephalosporins present a special problem. These drugs are generally categorized into three different groups (or generations). Although there is not always complete cross-resistance within each group, it is generally adequate to include only one of each in the sensitivity test (the one most used in clinical practice), e.g. cephalothin or cefazolin for the first generation; cefuroxime or cefamandole for the second generation; cefotaxime or ceftriaxone for the third generation. Ceftazidime, another third generation drug, is more active against Pseudomonas aeruginosa, and should only be included for testing this organism.

Among the presently commercialized fluoroquinolones, only one representative should be tested, e.g. ciprofloxacin or ofloxacin or pefloxacin. Cross-resistance can be assumed with norfloxacin which should only be tested (and used) for urinary and enteric pathogens.