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Use of cephalosporins for prophylaxis and therapy of polymicrobial infection in mice
1Naval Medical Research Institute, Bethesda, Maryland 20814-5055.
Abstract:
Cefoxitin, cefotetan, and cefmetazole were compared in 10-day therapy of intra-abdominal and subcutaneous infections caused by three organisms: Bacteroides fragilis and Bacteroides thetaiotaomicron combined with either Escherichia coli or Staphylococcus aureus. Intra-abdominal infection was caused by B. fragilis plus B. thetaiotaomicron plus E. coli. Therapy was initiated immediately before inoculation or was delayed for 8 h. Mortality was 14 of 30 (47%) for saline-treated mice, and all survivors developed abscesses. Immediate therapy reduced mortality and the percentage of mice with abscesses (in survivors), respectively, to 17 and 20% with cefoxitin, 0 and 13% with cefotetan, and 0 and 17% with cefmetazole, and the numbers of all bacteria were reduced by all the cephalosporins. Delayed therapy reduced mortality and abscess formation, respectively, to 20 and 8% of mice with cefoxitin, 10 and 93% with cefotetan, and 7 and 96% with cefmetazole. B. thetaiotaomicron survived in all abscesses treated with cefotetan and cefmetazole. Subcutaneous abscesses were caused by each organism alone or in combinations of one aerobe (S. aureus or E. coli) and one or two Bacteroides species. Early therapy reduced the numbers of all bacteria independent of their in vitro susceptibility. All agents reduced the number of each Bacteroides species with either E. coli or S. aureus. However, when therapy was delayed, cefotetan and cefmetazole were less effective than cefoxitin against B. thetaiotaomicron. Cefotetan was the most active agent against E. coli, and cefmetazole was the most effective against S. aureus. These data illustrate the efficacy of all tested cephalosporins in the prophylaxis of polymicrobial infections.
Insights
This study compared cefoxitin, cefotetan, and cefmetazole for treating polymicrobial infections in mice. All cephalosporins showed efficacy, with early treatment being most effective in reducing mortality and abscesses.
Area of Science:
- Infectious Diseases
- Microbiology
- Pharmacology
Background:
- Polymicrobial infections, particularly those involving anaerobic bacteria like Bacteroides species, pose significant therapeutic challenges.
- Intra-abdominal and subcutaneous infections often feature complex microbial communities requiring broad-spectrum antimicrobial agents.
Purpose of the Study:
- To compare the efficacy of cefoxitin, cefotetan, and cefmetazole in treating intra-abdominal and subcutaneous infections caused by specific Gram-negative and Gram-positive bacteria in a murine model.
- To evaluate the impact of immediate versus delayed therapy on treatment outcomes, including mortality and abscess formation.
Main Methods:
- A murine model was used to simulate intra-abdominal and subcutaneous infections caused by combinations of Bacteroides fragilis, Bacteroides thetaiotaomicron, Escherichia coli, and Staphylococcus aureus.
- Animals received either immediate or delayed (8-hour) treatment with cefoxitin, cefotetan, cefmetazole, or saline.
- Treatment efficacy was assessed by monitoring mortality rates, abscess development, and bacterial load.
Main Results:
- Immediate therapy with cefoxitin, cefotetan, and cefmetazole significantly reduced mortality and abscess formation compared to saline controls.
- Cefotetan and cefmetazole demonstrated superior efficacy in reducing mortality in intra-abdominal infections when therapy was immediate.
- Delayed therapy showed varying effectiveness, with cefoxitin generally outperforming cefotetan and cefmetazole against Bacteroides thetaiotaomicron, while cefotetan and cefmetazole showed specific activity against E. coli and S. aureus, respectively.
Conclusions:
- All tested cephalosporins demonstrated efficacy in the prophylaxis and treatment of polymicrobial infections in this model.
- The timing of antibiotic administration is critical, with immediate therapy yielding better outcomes.
- Specific cephalosporins may exhibit differential activity against certain components of polymicrobial infections, highlighting the importance of agent selection.