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.

Comparative prophylactic efficacies of ciprofloxacin, ofloxacin, cefazolin, and vancomycin in experimental model of staphylococcal wound infection.

Recent shifts in the species and antibiotic resistance patterns of bacteria causing nosocomial infections present new challenges for providing effective prophylaxis in surgery. Traditional regimens lack activity against methicillin-resistant staphylococci and many gram-negative species causing nosocomial infections. The new fluoroquinolones exhibit in vitro activity against many emerging surgical wound pathogens. To determine the potential of this class of antimicrobial agents for use in surgery, we compared the prophylactic efficacies of ciprofloxacin and ofloxacin with those of cefazolin and vancomycin in a guinea pig model of abscess formation. Four Staphylococcus aureus strains, one Staphylococcus epidermidis strain, and one Staphylococcus haemolyticus strain were evaluated. Vancomycin was the most effective prophylactic agent, exhibiting in vivo activity against all strains which was superior or equivalent to those of all other agents tested. Cefazolin was the least effective agent and surpassed the two quinolones in prophylactic efficacy against only one organism, a quinolone- and methicillin-resistant strain of S. aureus. The two quinolones provided excellent protection against infection with all but the quinolone-resistant isolate. The in vivo emergence of quinolone resistance among quinolone-susceptible isolates was not detected. The methicillin-resistant, quinolone-susceptible S. epidermidis and S. haemolyticus isolates were extremely susceptible to prophylaxis, exhibiting 50% infective doses above 4 x 10(6) CFU for seven of the eight antibiotic-strain combinations. We conclude that ciprofloxacin and ofloxacin may be effective antistaphylococcal agents in surgery. The role of these agents remains to be defined, and the definition should include consideration of an adverse effect upon antibiotic resistance patterns of organisms causing nosocomial infections.

Cefuroxime versus cefazolin as prophylaxis in vascular surgery.

Although cefazolin prophylaxis has proven efficacy in vascular surgery, Staphylococcus aureus wound infections are still an important postoperative complication. In cardiac surgery, cefazolin's susceptibility to hydrolysis by staphylococcal beta-lactamase has been proposed to account for some prophylaxis failures. To determine whether the incidence of vascular wound infections can be reduced by administering a more beta-lactamase-stable cephalosporin, we undertook a prospective, randomized trial of cefuroxime versus cefazolin. Cefuroxime was administered as a 1.5 gm dose before operation and 750 mg every 3 hours during operation. Cefazolin was given as 1 gm before operation and 500 mg every 4 hours during operation. Both agents were continued every 6 hours after operation for 24 hours. Deep wound infections developed in seven of 272 (2.6%) cefuroxime and three of 287 (1.0%) cefazolin recipients (p = 0.2). Staphylococcus aureus wound infections occurred in five cefuroxime versus two cefazolin recipients. In vitro evaluation of six of the study isolates plus an additional eight S. aureus strains from vascular wound infections showed greater susceptibility of the strains to cefazolin than cefuroxime (median minimal inhibitory concentrations of 0.5 and 2.0 micrograms/ml, respectively, p less than 0.05). Furthermore, despite its more frequent intraoperative redosing, cefuroxime exhibited lower trough serum concentrations than cefazolin. Among cefuroxime recipients, infection-associated procedures were significantly longer than infection-free procedures (p less than 0.05), suggesting that low tissue antibiotic concentrations may have contributed to the pathogenesis of these infections. In contrast, the length of the procedure was not a risk factor for infection among cefazolin recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Failure of cephalosporins to prevent Staphylococcus aureus surgical wound infections.

Approximately 35,000 Staphylococcus aureus surgical wound infections occur annually in the United States. To investigate why S aureus causes infection despite the perioperative administration of cephalosporins, we compared 35 methicillin-susceptible isolates recovered from deep wound infections that complicated cefazolin prophylaxis (18 of 1650 patients) and cefamandole prophylaxis (17 of 3702 patients) with 64 colonizing isolates from presurgical patients. Compared with both colonizing and cefamandole-associated isolates, S aureus isolates from cefazolin-associated infections were more resistant to cefazolin by specialized assays. Staphylococcus aureus isolates that produced the A and C variants of staphylococcal beta-lactamase were associated with infections following cefazolin and cefamandole prophylaxis, respectively. These isolates hydrolyze the respective cephalosporins rapidly, suggesting that staphylococcal survival after perioperative prophylaxis may be mediated by in vivo degradation of the prophylactically administered cephalosporin. These data indicate that some S aureus wound infections occur because of deficiencies in antimicrobial effectiveness that are not detectable by routine susceptibility tests. This finding has important implications for the therapy and prevention of S aureus infection.