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close this bookBasic Laboratory Procedures in Clinical Bacteriology (WHO; 1991; 128 pages)
View the documentPreface
View the documentIntroduction
open this folder and view contentsQuality assurance in microbiology
close this folderPart I. Bacteriological investigations
open this folder and view contentsBlood
open this folder and view contentsCerebrospinal fluid
open this folder and view contentsUrine
open this folder and view contentsStool
open this folder and view contentsLower respiratory tract infections
open this folder and view contentsUpper respiratory tract infections
open this folder and view contentsSexually transmitted diseases
open this folder and view contentsPurulent exudates, wounds, and abscesses
open this folder and view contentsAnaerobic bacteriology
close this folderAntimicrobial susceptibility testing
View the documentIntroduction
View the documentGeneral principles of antimicrobial susceptibility testing
View the documentClinical definition of terms “resistant” and “susceptible”: the three-category system
View the documentIndications for routine susceptibility tests
View the documentChoice of drugs for routine susceptibility tests in the clinical laboratory
View the documentThe modified Kirby-Bauer method
View the documentDirect versus indirect susceptibility tests
View the documentTechnical factors influencing the size of the zone in the disc diffusion method
View the documentQuality control
open this folder and view contentsPart II. Essential media and reagents for isolation and identification of clinical pathogens
View the documentSelected further reading
View the documentSelected WHO publications of related interest
View the documentBack Cover
 

Choice of drugs for routine susceptibility tests in the clinical laboratory

The choice of drugs used in a routine antibiogram is governed by considerations of the antibacterial spectrum of the drugs, their pharmacokinetic properties, toxicity, efficacy, and availability, as well as their cost to both the patient and the community. Among the many antibacterial agents that could be used to treat a patient infected with a given organism, only a limited number of carefully selected drugs should be included in the susceptibility test.

Table 12 indicates the drugs to be tested in various situations. The drugs in the table are divided into two sets. Set 1 includes the drugs that are available in most hospitals and for which routine testing should be carried 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 antibiotics 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 representative of each group of antimicrobials 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

 

1International Nonproprietary Names for Pharmaceutical Substances, Cumulative List No. 7. Geneva, World Health Organization, 1988.

Table 12. Basic sets of drugs for routine susceptibility testsa

 

Staphylococcus

Enterobacteriaceae

Pseudomonas aeruginosa

   

Intestinal

Urinary

Blood and tissues

 

Set 1
First choice

benzylpenicillin
oxacillin
erythromycin
tetracycline
chloramphenicol

ampicillin
chloramphenicol
co-trimoxazole
nalidixic acid
tetracycline

sulfonamide
trimethoprim
co-trimoxazole
ampicillin
nitrofurantoin
nalidixic acid
tetracycline

ampicillin
chloramphenicol
co-trimoxazole
tetracycline
cefalotin
gentamicin

piperacillin
gentamicin
tobramycin

Set 2
Additional drugs

gentamicin
amikacin
co-trimoxazole
clindamycin

norfloxacin

norfloxacin
chloramphenicol
gentamicin

cefuroxime
ceftriaxone
ciprofloxacin
piperacillin
amikacin

amikacin

 

a Notes on the individual antibacterial agents are given in the text.

1. The benzylpenicillin disc is used to test susceptibility to all β-lactamase-sensitive penicillins (such as oral phenoxymethylpenicillin and pheneticillin). Isolates of staphylococci that fall into the resistant category produce β-lactamase and should be treated with a β-lactamase-resistant penicillin or with another antibiotic, such as erythromycin.

2. Oxacillin. The oxacillin disc is representative or the whole group of β-lactamase-resistant penicillins (including meticillin, nafcillin, cloxacillin, dicloxacillin, and flucloxacillin). Moreover, there is good clinical evidence that cross-resistance exists between the meticillin and the cephalosporin 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 incubator is set at 35 °C1 or when the incubation time is prolonged.

A serious disadvantage of meticillin, as a representative disc for the β-lactamase-resistant penicillins, is its great lability even under conventional 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.

 

1 SAHM, D. F. et al. Current concepts and approaches to antimicrobial agent susceptibility testing. In: Cumitech 25, Washington, DC, American Society for Microbiology, 1988.

3. The results for the tetracycline disc may be applied to chlortetracycline, oxytetracycline, and other members of this group. However, most tetracycline-resistant staphylococci remain normally sensitive to minocycline. A disc of minocycline may thus be useful to test multiresistant strains of staphylococci.

4. The result with the chloramphenicol disc may be extrapolated to thiamphenicol, a related drug with a comparable antibacterial spectrum, but without known risk of aplastic anaemia.

5. Only one representative sulfonamide (sulfafurazole) is required in the test.

6. The co-trimoxazole disc contains a combination of trimethoprim and a sulfonamide (sulfamethoxazole). Although the use of combinations of drugs in discs has been condemned in previous WHO reports,2 co-trimoxazole is an exception because the two components of this synergistic combination have comparable pharmacokinetic properties and generally act “as a single drug”.

 

2 WHO Technical Report Series, No. 796, 1990 (The use of essential drugs: fourth report of the WHO Expert Committee).

7. Ampicillin is the prototype of a group of broad-spectrum penicillins with activity against many Gram-negative bacteria. As it is susceptible to β-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. (though amoxycillin is twice as active against salmonellae and only half as active against shigellae and H. influenzae).

8. Cefalotin. Only cefalotin needs to be tested routinely, as its spectrum is representative of all other first-generation cephalosporins (cefalexin, cefradine, cefaloridine, cefazolin, cefapirin). Where second- and third-generation cephalosporins 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, cefotaxime, ceftriaxone). Although some cephalosporins 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. This group of chemically related drugs 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 infections caused by resistant organisms.

11. Nitrofurantoin is limited to use only in the treatment of urinary tract infections, and should not be tested against microorganisms recovered from material other than urine.

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