Selection of beta-lactamase producers during cephalosporin and penicillin therapy

Treatment failures due to beta-lactamase producing strains of Enterobacter cloacae, Proteus vulgaris, Citrobacter freundii and Pseudomonas aeruginosa are frequently reported. It is difficult, however, to determine the underlying mechanism of resistance development. Different beta-lactam drugs, such as cephalosporins and penicillins have different ecological impacts on the infections and physiological flora of patients. They select in different ways although the mutation frequency of strains towards beta-lactamase production is not affected by these drugs. Thus in a specific process of selection one has to consider the mechanism and frequency of changes in the beta-lactamase production, the selective power of the different drugs (relation of drug concentration to the MIC for possible mutants or induction of beta-lactamase), selection of resistance in the physiological flora of patients, spread of such mutants to other patients and in the hospital environment, and the stability of beta-lactamase production. As each antibiotic has the potential of selecting mutants and in the case of beta-lactam drugs the more powerful ones select for mutants which produce a beta-lactamase that is more stable against less powerful drugs, a careful selection of drugs together with an effective infection control is mandatory.