Penicillins and beta-lactamase inhibitor combinations.

beta-Lactamase production by bacteria continues to be one of the main mechanisms of bacterial resistance to beta-lactam antibiotics, and it seems likely to remain so. beta-Lactamase inhibitors provide 1 strategy to overcome this mechanism of bacterial resistance. Although 3 beta-lactamase inhibitor/antibiotic combinations are currently available, only 1 is approved for veterinary use. Because the beta-lactamase inhibitor must be present concurrently with the antibiotic for synergistic activity, it is important to consider the pharmacokinetic profile of these drugs in combination. These combinations were developed and optimized for human patients, so it is unlikely that they would achieve the ideal plasma and tissue concentrations and ratios in veterinary patients. Indeed, several differences in pharmacokinetic variables of beta-lactam antibiotic/beta-lactamase inhibitor agents have been described in dogs, compared with people. Such pharmacokinetic differences should be considered when interpreting in vitro susceptibility results in veterinary species, because these tests use ratios of drug that were established for humans. The beta-lactamase inhibitors represent a successful example of targeted drug development. However, the currently available inhibitors are active primarily against class-A beta-lactamases. Because the frequency with which class-C beta-lactamases are recognized is rapidly increasing in human isolates, and because beta-lactamase enzymes continue to evolve, new beta-lactamase inhibitors will need to be developed to target these enzymes.