Evolution and resistance expression of MRSA. Evaluation of beta-lactam antibiotics against a set of isogenic strains with different types of phenotypic expression.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) has two mechanisms of resistance to beta-lactam antibiotics; one is mediated by mecA gene expression, and the other by penicillinase production. It has been generally accepted in the clinical field that beta-lactam antibiotics are not the drugs of choice for MRSA infection. In this report, however, ampicillin and penicillin G were shown to have relatively good activity against MRSA if combined with a beta-lactamase inhibitor, sulbactam. These beta-lactam antibiotics were found to have relatively high binding affinities to PBP2', the mecA-encoded MRSA-specific penicillin-binding protein. The possible therapeutic application of sulbactam/ampicillin against MRSA infection in combination with arbekacin, an aminoglycoside antibiotic newly developed and introduced into clinical use in Japan, is discussed.