Dilemmas of the beta-lactam explosion.

The development of new and more potent antimicrobics over the past few years has been profligate, and has surpassed the absorption threshold of the average clinician. This proliferation has not been limited to the new drugs with their empirically-determined advantages and shortcomings. Our understanding of principles and mechanisms of antimicrobial action, mechanisms of microbial resistance, means of overcoming microbial resistance, and related concepts has expanded at an equally rapid rate. This "explosion" of new antimicrobics and information not only poses dilemmas for clinicians; the laboratorian and infection control practitioner are also faced with new problems. The beta-lactam antibiotics, because of their clinical safety, have led the development parade and serve as excellent examples of the dilemmas we face. The recently released "third generation" cephalosporins (cefoperazone, cefotaxime, and moxalactam) are markedly more active against most microbes than earlier members of this family. Although most third generation compounds are similar in many respects, there are some significant differences among them. In the antimicrobial spectrum, for example, moxalactam exhibits the best in vitro activity against Bacteroides fragilis; cefoperazone has the highest activity against Pseudomonas aeruginosa; and cefotaxime is superior against non-enterococcal streptococci, Haemo-philus influenzae, and gonococci—including beta-lacta-mase-producing strains. Although cefatoxime has greater activity against staphylococci than the other two drugs, this activity is still less than that of cephalothin. Like cefoxitin, cefotaxime and moxalactam exhibit remarkable stability to most bacterial beta-lactamases. Cefoperazone is less stable, but still superior to the second generation cephalosporin, cefamandole. The pharmacokinetics of the three drugs also differ. There is some evidence to indicate that cefotaxime and E1MTORIAL moxalactam may enter the cerebrospinal fluid in effective concentrations (10-30% of peak serum concentrations)—a characteristic not present in earlier cephalosporins. These new beta-lactam antibiotics significantly increase the clinician's potential to treat a greater number of serious infections with a single safe drug. But, at the same time, the parameters that must be considered for rational drug selection and use have become more numerous and complex. One cannot assume that all "third generation" cephalosporins are alike and can be used interchangeably —a principle that will be more striking as other newer cephalosporins become available. Nor can one assume that the latest cephalosporins are superior—or even comparable—to the older drugs in all situations, e.g. staphylococcal infections, for which the "first generation" cephalosporins remain the drugs of choice. Cost is another important consideration in selection of drugs, and many infections will respond equally well …