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Comparative in vivo efficiency of cefamandole and cefoxitin against Bacteroides fragilis
Abstract:
An experimental model, where fibrin clots were inserted subcutaneously in rabbits, was adapted to study the in vivo efficacy of two cephalosporins against Bacteroides fragilis. The respective MIC's of cefamandole and cefoxitin against the microorganism were 16 microgram/ml and 1 microgram/ml. The clots were infected with 10(7) B. fragilis. Groups of seven animals received an intravenous bolus injection (100 mg/kg) of either drug. The serum levels of both drugs were similar to those seen in humans. The peak concentrations of cefamandole (40 microgram/mg) in the clots were found to be ten times higher than those of cefoxitin (4 microgram/mg). The log number of colony forming units in the clots averaged 7.5 at 0 h. At 6 hours, this number reached 8 in the untreated animals, 1.5 after cefoxitin, and 1.7 after cefamandole. The apparent in vitro superiority of cefoxitin against B. fragilis could not be demonstrated in vivo. This discrepancy between in vitro and in vivo data can be explained by the high degree of penetrance of cefamandole into the infected fibrin loci. In this animal system, both cefoxitin and cefamandole had similar in vivo activity against B. fragilis.
Insights
Cefoxitin shows higher in vitro activity against Bacteroides fragilis, but cefamandole demonstrates superior penetration into infected clots in rabbits. Both cephalosporins exhibit similar in vivo efficacy against B. fragilis in this experimental model.
Area of Science:
- Pharmacology
- Microbiology
- Infectious Diseases
Background:
- Bacteroides fragilis is a common cause of serious infections.
- Cephalosporins are frequently used to treat these infections.
- Understanding in vivo efficacy is crucial for optimal treatment selection.
Purpose of the Study:
- To compare the in vivo efficacy of cefamandole and cefoxitin against Bacteroides fragilis.
- To investigate the discrepancy between in vitro and in vivo activity.
- To evaluate drug penetration into infected fibrin clots.
Main Methods:
- An experimental subcutaneous fibrin clot model in rabbits infected with B. fragilis.
- Intravenous administration of cefamandole and cefoxitin (100 mg/kg).
- Measurement of drug concentrations in serum and clots, and bacterial colony-forming units (CFUs).
Main Results:
- Cefoxitin had a lower minimum inhibitory concentration (MIC) than cefamandole against B. fragilis in vitro.
- Cefamandole achieved significantly higher concentrations in infected clots compared to cefoxitin.
- Both cefoxitin and cefamandole demonstrated similar reduction in B. fragilis CFUs in vivo, despite in vitro differences.
Conclusions:
- In vitro activity does not always predict in vivo efficacy for cephalosporins against B. fragilis.
- Cefamandole's superior penetration into infected fibrin clots contributes to its comparable in vivo performance.
- This study highlights the importance of considering drug distribution in infected tissues for antibiotic selection.
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