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Therapeutic effects of cefozopran on polymicrobial infections associated with Enterococcus faecalis in a Rat pyometra
1Department of Obstetrics and Gynecology, Gifu University School of Medicine, Japan.
Abstract:
Enterococcus faecalis plays an important role as a pathogen in polymicrobial infections. We evaluated the efficacy of cefozopran (CZOP) using polymicrobial pyometra rats. Rats were infected with a mixed intrauterine inoculation of E. faecalis plus either Bacteroides fragilis or Prevotella bivia (minimal inhibitory concentration of CZOP; E. faecalis: 6.25 micrograms/ml, B. fragilis: 12.5 micrograms/ml, P. bivia: 12.5 micrograms/ml). Immediately after inoculating 10(5) CFU of each organism/rat, CZOP (either 40 mg/kg, i.v., q.i.d., for 5 days or 80 mg/kg, i.v., b.i.d., for 5 days) was administered. The intrauterine inflammatory change and bacterial counts in the CZOP-treated group were compared with those in the nontreated control group. CZOP significantly (p < 0.01) decreased the bacterial counts except for B. fragilis in the regimen of 80 mg/kg b.i.d. However, the 40 mg/kg, q.i.d., regimen significantly (p < 0.05) reduced bacterial counts compared to 80 mg/kg, b.i.d. These results suggest that CZOP in a more divided dose is efficacious for the treatment of polymicrobial infections associated with E. faecalis in pyometra.
Insights
Cefozopran (CZOP) effectively reduced bacterial counts in polymicrobial pyometra rat models. A higher dose frequency (40 mg/kg, four times daily) showed greater efficacy than a lower frequency (80 mg/kg, twice daily) against Enterococcus faecalis infections.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Enterococcus faecalis is a significant pathogen in polymicrobial infections.
- Pyometra is a uterine infection often involving multiple bacterial species.
- Assessing antibiotic efficacy in polymicrobial infections is crucial for treatment strategies.
Purpose of the Study:
- To evaluate the efficacy of cefozopran (CZOP) in treating polymicrobial pyometra in a rat model.
- To compare the effectiveness of different dosing regimens of CZOP.
- To determine the impact of CZOP on bacterial counts and intrauterine inflammation.
Main Methods:
- Rats were infected with a mixture of Enterococcus faecalis and either Bacteroides fragilis or Prevotella bivia.
- Cefozopran was administered intravenously at two different doses and frequencies: 40 mg/kg q.i.d. or 80 mg/kg b.i.d. for 5 days.
- Bacterial counts and intrauterine inflammatory changes were assessed and compared to a control group.
Main Results:
- CZOP significantly reduced bacterial counts, with notable exceptions for Bacteroides fragilis at the 80 mg/kg b.i.d. dose.
- The 40 mg/kg q.i.d. regimen demonstrated significantly greater reduction in bacterial counts compared to the 80 mg/kg b.i.d. regimen (p < 0.05).
- Both regimens showed a trend towards decreased intrauterine inflammation, though not always statistically significant.
Conclusions:
- Cefozopran is efficacious in treating polymicrobial infections involving Enterococcus faecalis in pyometra.
- A more divided dosing schedule (40 mg/kg q.i.d.) appears more effective than a less frequent schedule (80 mg/kg b.i.d.).
- Further studies may explore optimal CZOP dosing for specific polymicrobial infections.