Comparison of single and combination antimicrobial agents for prevention of experimental gas gangrene caused by Clostridium perfringens

Abstract

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).

Bacterial, Fungal, Parasitic, and Viral Myositis

“…Repeat surgical evaluations are often necessary to ensure that all infected and necrotic tissues have been adequately debrided. Antibiotic coverage is the same as for GAS necrotizing myositis, with both high-dose penicillin G and clindamycin (225). Since gas gangrene oftentimes arises from dirty wounds and involves other organisms in addition to Clostridium spp.…”

Clostridium perfringensinvasiveness is enhanced by effects of theta toxin upon PMNL structure and function: The role of leukocytotoxicity and expression of CD11/CD18 adherence glycoprotein

“…A viable inoculum containing washed, log phase C. perfringens was prepared as previously described [11]. A killed bacterial inoculum was prepared by placing 15 ml of washed, log phase bacteria (2.8 x l0 s cfu ml -~) in a sterile, covered, 100 mm Petri dish in a drying oven at 60°C for 30 min.…”

“…Such perfusion deficits would not only create an anaerobic environment optimal for clostridial growth but would contribute to the rapidly expanding margins of tissue destruction so characteristic of clostridial gangrene. Thus, therapeutic strategies directed against theta toxin expression in vivo, such as neutralization of theta toxin with specific anti-toxin antibody [51] or inhibition of theta toxin synthesis [11], may be valuable adjuncts to traditional antimicrobial regimens. These results also suggest that agents which neutralize endogenous proadhesive molecules may alleviate toxin-in-duced vascular leukostasis and resultant tissue injury in C. perfringens infection.…”

Comparative in vitro Bactericidal Activity of 24 Antimicrobial Drugs against <i>Clostridium perfringens</i>

“…Furthermore, Stevens et al [7] noted that combination antimicrobial chemotherapy of experimental C. perfrin gens infection was not superior to mono therapy with either metronidazole or clin damycin. On the other hand, we noted [9,10] that imipenem, but not ciprofloxacin, clindamycin, penicillin G, and rifampin, was effective in cases of experimental (murine) gas gangrene that had been evoked with large inocula of several mouse-'virulent' strains of C. perfringens.…”

“…7 and 10 for additional literature]. Lately, two laboratories reexamined the in vitro and in vivo (experimental murine gas gangrene) susceptibility of C. perfringens to penicillin G as compared with some newer antimicrobial drugs [7][8][9][10][11][12].…”