BETA-LACTAMASE PRODUCTION DIMINISHES THE PROPHYLACTIC EFFICACY OF AMPICILLIN AND CEFAZOLIN IN A GUINEA-PIG MODEL OF STAPHYLOCOCCUS-AUREUS WOUND-INFECTION

Clinical trials in surgery suggest that some failures of antibiotic pr ophylaxis are related to the in vivo degradation of beta-lactams by St aphylococcus aureus beta-lactamase. To explore this issue further, iso geneic isolates of S. aureus differing only in whether they contained the structural gene for type A staphylococcal beta-lactamase were cons tructed and compared for their ability to establish an abscess in a gu inea pig model. With ampicillin prophylaxis, the ID50 was 870 cfu for the beta-lactamase-negative isolate VK7114 and 240 cfu for the beta-la ctamase-producing isolate VK7115 (P < .001). Similarly, the ID50 was g reater for the beta-lactamase-negative isolate when cefazolin prophyla xis was administered (599 vs. 128 cfu, VK7114 and VR7115; P < .001). I n the setting of prophylaxis with (beta)-lactamase-susceptible antibio tics, beta-lactamase contributes to the pathogenesis of S. aureus woun d infections.