Beta-lactam antibiotics and beta-lactamases: two sides of a continuing story.

The period since the introduction of beta-lactam antibiotics for therapeutic purposes has been characterized by a number of phases during which the incidence of resistant bacteria causing clinical infections has been high. Initially, penicillin-resistant staphylococci were the problem; more recently, it has been the resistant gram-negative bacteria, including anaerobes, that have given cause for concern. Thus novel beta-lactam antibiotics with activity against the resistant organisms have been developed. For the staphylococci methicillin, oxacillin, and cloxacillin were introduced, and for gram-negative species, cefuroxime and cefoxitin. Cefoxitin is particularly useful for treatment of infections due to anaerobes and ampicillin-resistant isolates of Escherichia coli. In all cases the best way to achieve efficacy against resistant bacteria seems to have been to design antibiotics that are insensitive to hydrolysis by beta-lactamases.