Gas gangrene caused by Clostridium perfringens is associated with significant mortality and morbidity in spite of penicillin treatment. Although prompt surgical debridement has been established as the primary therapeutic objective, additional studies are needed for determination of the optimal antimicrobial therapy. In a mouse model of gas gangrene caused by Clostridium perfringens, clindamycin, metronidazole, rifampin, and tetracycline were all more efficacious than penicillin (P less than .05). Survival of penicillin-treated mice was not significantly better than that of untreated controls in spite of serum levels that ranged up to 77-1,800 micrograms/ml. Responses to metronidazole were highly dose dependent. For example, 60% of mice survived after 75 mg of metronidazole/kg, but only 10% survived after 19 mg/kg. In contrast, clindamycin was highly effective over a broad dosing range (8.6-86 mg/kg). The efficacy of all antibiotics was reduced if treatment was delayed or larger inocula of bacteria were used.
The treatment of experimental gas gangrene caused by Clostridium perfringens was investigated by using combinations of antimicrobial agents. This study demonstrated that rifampin, penicillin, metronidazole, and clindamycin were all bactericidal against standard inocula (105 to 106 CFU). These antimicrobial agents were then administered to mice beginning 30 min after intramuscular injection of 109 CFU of C. perfringens type A.The highest doses used produced levels of drug in blood which exceeded the MIC by at least a factor of 40. In addition, other groups of mice received monotherapy at full dose or one-fourth full dose or combination antimicrobial therapy at full or one-fourth full dose. Among the single and combination antimicrobial treatments, metronidazole alone, clindamycin alone, and clindamycin plus penicillin were the most efficacious (P < 0.05). Although the survival of mice treated with clindamycin plus penicillin was greater than that of mice treated with clindamycin alone, the difference did not reach statistical significance (P > 0.05). In contrast, mice treated with a combination of metronidazole and penicillin demonstrated greater mortality than those treated with metronidazole alone (P < 0.05). In summary, combination antimicrobial therapy of experimental C. perfringens infection did not improve survival compared to that achieved with metronidazole or clindamycin alone, and some combinations significantly reduced survival (P < 0.05).
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