Staphylococcus Enterobacteriaceae Pseudomonas
Intestinal Urinary Blood & tissues
aeruginosa
Set 1 benzylpenicillin ampicillin sulfonamide ampicillin piperacillin First choice oxacillin chloramphenicol trimethoprim chloramphenicol gentamicin erythromycin co-trimoxazole co-trimoxazole co-trimoxazole tobramycin tetracycline nalidixic acid ampicillin tetracycline
chloramphenicol tetracycline nitrofurantoin cefalotin nalidixic acid gentamicin tetracycline amoxy-clavb
Set 2 gentamicin norfloxacin norfloxacin cefuroxime amikacin Additional drugs amikacin chloramphenicol ceftriaxone ciprofloxacin
co-trimoxazole gentamicin ciprofloxacin ceftazidine
clindamycin amoxy-clavb
piperacillin
nitrofurantoin amikacin
a
Notes on the individual antimicrobial agents are given in the text. b
out for every strain. Tests for drugs in set 2 are to be performed only at the special request of the physician, or when the causative organism is resistant to the first-choice drugs, or when other reasons (allergy to a drug, or its unavailability) make further testing justified. Many antimicrobials with good clinical activity have been omitted from the table, but it must be emphasized that they are rarely needed in the management of the infected patient. In very rare cases, one or more additional drugs should be included when there is a special reason known to the physician, or when new and better drugs become available. Periodic revision of this table is therefore desirable, and this should be done after appropriate discussions with clinical staff. Many problems arise in practice, because clinicians are not always aware that only one representa- tive of each group of antimicrobial agents is included in routine tests. The result obtained for this particular drug may then be extrapolated to all, or most, of the other members of the group. Difficulties arise in some countries when the physician is familiar only with the commercial brand name of the drug and not with its generic nonproprietary name. A serious effort should be made to inform medical personnel about the international nonproprietary names of pharmaceutical substances, and to encourage their use.1
1. The benzylpenicillin disc is used to test susceptibility to all b-lactamase- sensitive penicillins (such as oral phenoxymethylpenicillin and pheneti- cillin). Isolates of staphylococci that fall into the resistant category produce b-lactamase and should be treated with a b-lactamase-resistant penicillin G or with another antimicrobial, such as erythromycin. 2. The oxacillin disc is representative of the whole group of b-lactamase-
resistant penicillins (including meticillin, nafcillin, cloxacillin, dicloxacillin, and flucloxacillin). There is good clinical evidence that cross-resistance exists between the meticillin and the cefalosporin groups. Therefore, it is useless and misleading to include cefalotin in the antibiogram for staphylococci.
Resistance to meticillin and related drugs is often of the heterogeneous type, i.e. the majority of cells may be fully susceptible and produce a wide inhibition zone, while the resistant part of the population appears in the form of minute discrete colonies growing within the inhibition zone. This type of resistance is more apparent when the temperature of the incuba- tor is set at 35 ∞C2or when the incubation time is prolonged.
A serious disadvantage of meticillin, as a representative disc for the b- lactamase-resistant penicillins, is its great lability even under conven- tional storage conditions. The oxacillin disc is much more resistant to deterioration and is therefore preferred for the standardized diffusion test. The cloxacillin and dicloxacillin discs are not used as they may not indicate the presence of a heteroresistant strain.
3. The results for the tetracycline disc may be applied to chlortetracycline, oxytetracycline, and other members of this group. However, most tetra- cycline-resistant staphylococci remain normally sensitive to minocycline. A disc of minocycline may thus be useful to test multiresistant strains of staphylococci.
4. The result for the chloramphenicol disc may be extrapolated to thiam- phenicol, a related drug with a comparable antimicrobial spectrum, but without known risk of aplastic anaemia.
5. Only one representative of sulfonamide (sulfafurazole) is required in the test.
1 International Nonproprietary Names (INN) for Pharmaceutical Substances. Cumulative list
No. 9. Geneva, World Health Organization, 1996.
2 Sahm DF et al. Current concepts and approaches to antimicrobial agent susceptibility testing.
In: Cumitech 25, Washington, DC, American Society for Microbiology, 1988. ANTIMICROBIAL SUSCEPTIBILITY TESTING
BACTERIOLOGICAL INVESTIGATIONS
A 6. The co-trimoxazole disc contains a combination of trimethoprim and a sul-
fonamide (sulfamethoxazole). The two components of this synergistic combination have comparable pharmacokinetic properties and generally act as a single drug.
7. Ampicillin is the prototype of a group of broad-spectrum penicillins with activity against many Gram-negative bacteria. As it is susceptible to b- lactamase, it should not be used for testing staphylococci. Generally, the susceptibility to ampicillin is also valid for other members of this group: amoxycillin, pivampicillin, talampicillin, etc. (although amoxycillin is twice as active against salmonellae and only half as active against shigel- lae and H. influenzae).
8. Only cefalotin needs to be tested routinely as its spectrum is representa- tive of all other first-generation cefalosporins (cefalexin, cefradine, cefaloridine, cefazolin, cefapirin). Where second- and third-generation cefalosporins and related compounds (cefamycins) with an expanded spectrum are available, a separate disc for some of these new drugs may be justified in selected cases (cefoxitin, cefamandole, cefuroxime, cefo- taxime, ceftriaxone). Although some cefalosporins can be used to treat severe staphylococcal infections, the susceptibility of the infecting strain can be derived from the result with oxacillin as already mentioned under 2 above.
9. Erythromycin is used to test the susceptibility to some other members of the macrolide group (oleandomycin, spiramycin).
10. Aminoglycosides form a group of chemically related drugs that includes streptomycin, gentamicin, kanamycin, netilmicin and tobramycin. Their antimicrobial spectra are not always closely enough related to permit assumption of cross-resistance, but against susceptible pathogens these agents have been shown to be equally effective. Numerous studies have compared the nephrotoxicity and ototoxicity of gentamicin, netilmicin and tobramycin, but there is no conclusive evidence that any one of the drugs is less toxic than the others. It is strongly recommended that each laboratory select a single agent for primary susceptibility testing. The other agents should be held in reserve for treatment of patients with infec- tions caused by resistant organisms.
11. Nitrofurantoin is limited to use only in the treatment of urinary tract infec- tions, and should not be tested against microorganisms recovered from material other than urine.
Table 24 provides information on zone diameter limits for control strains.