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Metronidazole and gentamicin prophylaxis in synergistic aerobe-anaerobe infections in mice
Abstract:
The efficacy of prophylaxis by intraperitoneal injection of gentamicin, metronidazole or both drugs combined was investigated in a mouse model of mixed infection with Escherichia coli and Bacteroides fragilis. A three dose prophylactic regimen given 12 hourly was studied starting simultaneously with bacterial challenge. Serum antibiotic concentrations lay within the human therapeutic ranges. Metronidazole alone eliminated B. fragilis from the developing infections, but at higher challenge doses the mice developed abscesses which contained E. coli, and mortality was no different from controls. Gentamicin alone eliminated both bacteria and deaths in all infections, but sterile abscesses occurred in two of five animals at the highest challenge dose. Mixed metronidazole + gentamicin abolished all effects of the challenge bacteria, aborting all infections for all challenge doses with no formation of sterile abscesses. It is proposed that, in abdominal surgery, although metronidazole or gentamicin may be effective given alone for low levels of contamination, for higher levels (e.g. colonic surgery) both drugs may be required.
Insights
Prophylactic antibiotics, gentamicin and metronidazole, were tested in mice. Combining both drugs effectively prevented infections from Escherichia coli and Bacteroides fragilis, even at high doses.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Antibiotic prophylaxis is crucial in preventing surgical site infections.
- Mixed bacterial infections, common in abdominal surgery, pose treatment challenges.
Purpose of the Study:
- To evaluate the prophylactic efficacy of gentamicin, metronidazole, or their combination against a mixed infection model.
- To determine the optimal antibiotic regimen for preventing infections caused by Escherichia coli and Bacteroides fragilis.
Main Methods:
- A mouse model was used to simulate mixed infections with Escherichia coli and Bacteroides fragilis.
- A three-dose prophylactic regimen of intraperitoneal antibiotics was administered 12-hourly, starting concurrently with bacterial challenge.
- Serum antibiotic concentrations were measured to ensure they fell within human therapeutic ranges.
Main Results:
- Metronidazole alone eradicated B. fragilis but did not prevent abscesses or reduce mortality at higher challenge doses.
- Gentamicin alone eradicated both bacteria and prevented deaths, though sterile abscesses formed in some cases.
- The combination of metronidazole and gentamicin completely abolished all infection effects, preventing abscesses and mortality across all challenge doses.
Conclusions:
- For low-level contamination in abdominal surgery, single-agent prophylaxis with metronidazole or gentamicin may suffice.
- Higher contamination levels, such as those in colonic surgery, necessitate the combined use of metronidazole and gentamicin for effective prophylaxis.
- Combined antibiotic therapy offers superior protection against polymicrobial infections in surgical settings.