rifampin and Gas-Gangrene

Five antimicrobial drugs (ciprofloxacin, clindamycin, imipenem, penicillin G, and rifampin) were examined for therapeutic efficacy in a murine model gas gangrene due to Clostridium perfringens type A, following infection with large bacterial inocula. Imipenem was effective against all 6 strains of C. perfringens; conversely, penicillin G failed against these 6 strains. Ciprofloxacin, clindamycin, and rifampin occupied intermediate positions.

Topics: Animals; Ciprofloxacin; Clindamycin; Clostridium perfringens; Disease Models, Animal; Gas Gangrene; Imipenem; Mice; Microbial Sensitivity Tests; Penicillin G; Rifampin

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.

Topics: Animals; Anti-Bacterial Agents; Clindamycin; Clostridium perfringens; Female; Gas Gangrene; Male; Metronidazole; Mice; Penicillin G; Rifampin; Tetracycline

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 (10(5) to 10(6) CFU). These antimicrobial agents were then administered to mice beginning 30 min after intramuscular injection of 10(9) 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 less than 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 greater than 0.05). In contrast, mice treated with a combination of metronidazole and penicillin demonstrated greater mortality than those treated with metronidazole alone (P less than 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 less than 0.05).

Topics: Animals; Clindamycin; Clostridium perfringens; Drug Therapy, Combination; Female; Gas Gangrene; Male; Metronidazole; Mice; Microbial Sensitivity Tests; Penicillin G; Rifampin

The inhibitory effect of rifampicin against most of 82 strains of pathogenic Clostridia was evident at a concentration of less than 0.1 gamma/ml. The bactericidal concentrations were close to the bacteriostatic ones with respect to 74 strains. The protective effect of rifampicin in mice with experimental anaerobic gaseous infaction caused by different species of pathogenic Clostridia was evident at doses of 0.5 mg/kg. In infections caused by associations of Clostridia and Staph. aureus resistant to other antibiotics, rifampicin was effective, while ampicillin had no protective effect. Rifampicin administered 24 to 96 hours before the infection prevented the specific process. A number of other antibiotics, such as ampicillin, cephaloridin, morphocycline and 7-chlor-7-desoxylincomycin had no such a capacity. The prolonged prophylactic effect of rifampicin was associated with maintenance of low antibiotic levels in the blood and muscle tissues which were higher than the minimum inhibitory concentrations. The effect of rifampicin against the background of a rapidly developing process was less pronounced and limited in time.

Topics: Animals; Anti-Bacterial Agents; Clostridium; Clostridium perfringens; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Gas Gangrene; In Vitro Techniques; Mice; Microbial Sensitivity Tests; Rabbits; Rifampin; Time Factors

Topics: Animals; Clostridium; Drug Resistance, Microbial; Gas Gangrene; Guinea Pigs; Rifampin