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Failure of cephalosporins to prevent Staphylococcus aureus surgical wound infections
D S Kernodle1, D C Classen, J P Burke
1Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tenn.
Abstract:
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.
Insights
Some Staphylococcus aureus (S. aureus) wound infections persist despite antibiotic prophylaxis. This occurs due to bacterial resistance mechanisms, like beta-lactamase production, that degrade antibiotics, impacting treatment effectiveness.
Area of Science:
- Infectious Diseases
- Microbiology
- Surgical Infection Prevention
Background:
- Staphylococcus aureus is a common cause of surgical wound infections in the US.
- Cephalosporins are routinely used for perioperative prophylaxis to prevent S. aureus infections.
- Breakthrough infections suggest limitations in current prophylactic strategies.
Purpose of the Study:
- To investigate the mechanisms by which S. aureus causes infections despite cephalosporin prophylaxis.
- To compare bacterial isolates from infections and colonization to identify resistance factors.
- To understand the role of staphylococcal beta-lactamase in treatment failure.
Main Methods:
- Compared methicillin-susceptible S. aureus isolates from cefazolin- and cefamandole-associated infections with colonizing isolates.
- Utilized specialized assays to determine cefazolin resistance.
- Identified staphylococcal beta-lactamase variants (A and C) in isolates.
Main Results:
- S. aureus isolates from cefazolin-associated infections showed increased resistance to cefazolin compared to other groups.
- Isolates producing staphylococcal beta-lactamase A were linked to cefazolin prophylaxis failures.
- Isolates producing staphylococcal beta-lactamase C were linked to cefamandole prophylaxis failures.
- These beta-lactamase variants rapidly hydrolyzed their respective cephalosporins.
Conclusions:
- In vivo degradation of cephalosporins by staphylococcal beta-lactamase contributes to S. aureus survival.
- Some S. aureus wound infections result from antimicrobial resistance not detected by standard tests.
- Findings have significant implications for preventing and treating S. aureus surgical site infections.