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 prophylaxis are related to the in vivo degradation of beta-lactams by Staphylococcus aureus beta-lactamase. To explore this issue further, isogeneic isolates of S. aureus differing only in whether they contained the structural gene for type A staphylococcal beta-lactamase were constructed and compared for their ability to establish an abscess in a guinea pig model. With ampicillin prophylaxis, the ID50 was 870 cfu for the beta-lactamase-negative isolate VK7114 and 240 cfu for the beta-lactamase-producing isolate VK7115 (P < .001). Similarly, the ID50 was greater for the beta-lactamase-negative isolate when cefazolin prophylaxis was administered (599 vs. 128 cfu, VK7114 and VK7115; P < .001). In the setting of prophylaxis with beta-lactamase-susceptible antibiotics, beta-lactamase contributes to the pathogenesis of S. aureus wound infections.
Kernodle
D S
DS
Department of Medicine, Vanderbilt University School of Medicine, and VA Medical Center, Nashville, Tennessee 37232-2605, USA. kernodds@ctrvax.vanderbilt.edu
Voladri
R K
RK
Kaiser
A B
AB
D000038:Abscess / Q000188:drug therapy; D000667:Ampicillin / Q000627:therapeutic use*; D000818:Animals; D019072:Antibiotic Prophylaxis; D002437:Cefazolin / Q000627:therapeutic use*; D002511:Cephalosporins / Q000627:therapeutic use; D005260:Female; D005798:Genes, Bacterial; D006168:Guinea Pigs; D008297:Male; D008826:Microbial Sensitivity Tests; D016296:Mutagenesis; D010406:Penicillins / Q000627:therapeutic use; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000201:enzymology; D014946:Wound Infection / Q000188:drug therapy* / Q000201:enzymology; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000235:genetics
D002511:Cephalosporins; D010406:Penicillins; D000667:Ampicillin; D001618:beta-Lactamases; D002437:Cefazolin