BINDING-AFFINITY FOR PENICILLIN-BINDING PROTEIN-2A CORRELATES WITH INVIVO ACTIVITY OF BETA-LACTAM ANTIBIOTICS AGAINST METHICILLIN-RESISTANT STAPHYLOCOCCUS-AUREUS

The β-lactam antibiotics ticarcillin, nafcillin, imipenem, and ampicillin, which differ in antibacterial activity against methicillin-resistant strains of Staphylococcus aureus, were examined for affinity to penicillin-binding protein (PBP) 2a, which mediates methicillin resistance. The relative efficacy ofeach antibiotic was compared to vancomycin in a rabbit model of aortic valve endocarditis caused by either a methicillin-susceptible or methicillin-resistant strain of β-lactamase-producing S. aureus. β-lactamase inhibitors clavulanate and sulbactam were used in combination with ticarcillin and ampicillin, respectively. All β-lactam antibiotics were effective against the susceptible strain. β-lactam antibiotic activity in vitro and in vivo against the resistant strain correlated with its affinity forbinding to PBP2a. Lack of efficacy of β-lactam antibiotics for the resistant strain wasdue to an inability to eradicate the resistant sub population of cells. Vancomycin was the most effective agent. © 1990, by The University of Chicago.