Microbiological investigation of cephalosporins

The most important role of the clinical microbiology laboratory is to advise clinicians in their choice of antimicrobial therapy. While the application of modern laboratory techniques is enabling sensitivity testing to cephalosporins to be performed with increasing precision, the ability to predict accurately clinical efficacy has not improved in parallel. For the cephem group in particular, the present confusion as to the numerical value of breakpoints and their interpretation, and the overuse of 'class testing' are making the task of the clinical microbiologist more difficult. For most purposes, simple disc sensitivity testing of cephems gives sufficient information, and it is simple to carry out, as no special media or growth conditions are required. Further studies are required to answer an outstanding question of great importance, namely, what the clinical prognostic significance is of results of sensitivity testing of 'methicillin-resistant' Staphylococcus aureus and coagulase-negative staphylococci, as these organisms often appear sensitive to cephems in vitro. For the research worker, the cephems provide tools of almost unrivalled power in the investigation of such microbiologically important topics as cell wall synthesis, bacteriolysis, membrane function and various aspects of enzyme regulation and inhibition. Relatively minor changes in the structure of cephem molecules can markedly affect their binding to bacteria, thus allowing probing of the functions of the individual penicillin-binding proteins. In Gram-negative bacteria, membrane function can be selectively changed by the action of subinhibitory concentrations of cephems, as it is intimately connected to the integrity of the peptidoglycan moiety. Induction and derepression of beta-lactamases may be responsible for a new type of bacterial resistance.