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Cefpirome, alone and in combination with gentamicin for enterococcal pyelonephritis in the rodent model
F L Sapico1, V J Ginunas, J Z Montgomerie
1Department of Medicine, University of Southern California School of Medicine, Los Angeles.
Abstract:
The in vitro and in vivo activity of cefpirome (CF) against Enterococcus faecalis GK strain was examined. The ratio of minimal inhibitory to bactericidal concentration (MIC/MBC) values in microgram/ml were (a) ampicillin 0.8/1.5; (b) gentamicin 2/25; (c) vancomycin, 0.8/50; and (d) CF, 8/32. A time-kill study using 10(7) organisms per milliliter showed a drop of 3 logs10 at 4 hr in the tube containing cefpirome (10 micrograms/ml) as well as the tube containing cefpirome (5 micrograms/ml) plus gentamicin (GM) (2 micrograms/ml), as compared to the control and the tube containing GM at 4 micrograms/ml. At 8 and 24 hr, however, regrowth to control levels occurred. Of this enterococcal strain consisting of 10(8) organisms, 1 ml was then injected intravenously by tail vein into 150 male Wistar rats weighing 120 g each. Eleven days after injection, 10 rats were killed and the remaining ones were randomized into four treatment groups: (a) untreated control; (b) BM, 0.9 mg; (c) CF, 10 mg; and (d) CF + GM. The rats received the injections intramuscularly twice daily. At least 10 rats from each group were killed for quantitative kidney cultures at 1, 2, and 4 weeks after start of therapy. At the end of 4 weeks of therapy, the results were significantly better in the combination group compared to the other three groups.
Insights
The study investigated cefpirome (CF) and gentamicin (GM) against Enterococcus faecalis. Combination therapy showed improved in vivo efficacy in a rat model, suggesting potential for treating enterococcal infections.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Enterococcus faecalis is a significant cause of hospital-acquired infections.
- Antibiotic resistance in E. faecalis necessitates the evaluation of novel therapeutic strategies.
- Cefpirome (CF) is a cephalosporin antibiotic with demonstrated in vitro activity.
Purpose of the Study:
- To evaluate the in vitro and in vivo activity of cefpirome (CF) against a specific strain of Enterococcus faecalis (GK strain).
- To assess the efficacy of cefpirome alone and in combination with gentamicin (GM) in a rat model of E. faecalis infection.
Main Methods:
- Minimal inhibitory and bactericidal concentrations (MIC/MBC) were determined for CF, ampicillin, gentamicin, and vancomycin.
- Time-kill studies were conducted to assess the bactericidal activity of CF and CF + GM.
- A rat model of intravenous E. faecalis infection was established, followed by treatment with control, BM, CF, or CF + GM, with subsequent quantitative kidney cultures.
Main Results:
- Cefpirome exhibited MIC/MBC values of 8/32 µg/ml against E. faecalis GK strain.
- In vitro time-kill studies showed a 3-log10 drop at 4 hours with CF (10 µg/ml) and CF (5 µg/ml) + GM (2 µg/ml), though regrowth occurred by 24 hours.
- In vivo, the combination therapy of cefpirome and gentamicin demonstrated significantly better results in reducing kidney bacterial burden after 4 weeks compared to monotherapy or untreated controls.
Conclusions:
- Cefpirome alone has limited bactericidal activity against this E. faecalis strain.
- The combination of cefpirome and gentamicin shows enhanced efficacy in eradicating E. faecalis in a preclinical in vivo model.
- Combination therapy warrants further investigation for the treatment of enterococcal infections.