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Effect of antibiotics on toxin production and viability of Clostridium perfringens
Abstract:
We have recently reported (D.L. Stevens, K.A. Maier, B.M. Laine, and J.E. Mitten, J. Infect. Dis. 155:220-228, 1987) that clindamycin, rifampin, and tetracycline were more efficacious than penicillin in the treatment of fulminant gas gangrene in mice caused by Clostridium perfringens. We hypothesize that antibiotic efficacy correlated with bactericidal or toxin-suppressing properties of these agents. To investigate the possibility that penicillin is only bacteriostatic against C. perfringens, we performed macrobroth dilution MIC and MBC determinations using C. perfringens ATCC 13124. Mean MICs were equal to MBCs for the following antibiotics (micrograms per milliliter): clindamycin, 0.07; tetracycline, 0.05; rifampin, 0.03; metronidazole, 0.69; and penicillin, 0.27. The MIC/MBCs of chloramphenicol were 1.50/3.10 (micrograms/ml). Because antibiotic efficacy did not correlate with bactericidal activity, we measured alpha-toxin activity and found complete suppression of alpha-toxin activity by tetracycline, metronidazole, rifampin, clindamycin, and chloramphenicol at concentrations equal to the MIC. In contrast, alpha-toxin activity persisted at concentrations of penicillin equal to and above the MIC. The dynamics of bacterial killing and kinetics of alpha-toxin production were next studied in log-phase cultures of C. perfringens with antibiotic concentrations 10 times the MIC. Clindamycin, metronidazole, and rifampin all caused rapid reductions in viability, turbidity, and alpha-toxin activity by 15 to 45 min. In contrast, penicillin demonstrated slower bacterial killing, increased turbidity (62.6% of control), and persistent alpha-toxin activity (80% of control values) for 2 h. Tetracycline and chloramphenicol were the least effective in reducing viability; however, the turbidity of cultures did not increase, and alpha-toxin activity was not detectable. Toxin suppression and rapid bacterial killing may in part explain the observed superior therapeutic efficacy of clindamycin, rifampin, and metronidazole compared with penicillin in the treatment of experimental gas gangrene.
Insights
Penicillin showed less efficacy against gas gangrene in mice compared to other antibiotics. Superior antibiotics like clindamycin, rifampin, and metronidazole rapidly killed bacteria and suppressed toxin production, unlike penicillin.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Clindamycin, rifampin, and tetracycline demonstrated greater efficacy than penicillin in treating experimental gas gangrene caused by Clostridium perfringens.
- Antibiotic efficacy in gas gangrene treatment may correlate with bactericidal or toxin-suppressing properties.
Purpose of the Study:
- To investigate if penicillin's bacteriostatic properties contribute to its lower efficacy against Clostridium perfringens.
- To compare the bactericidal activity and alpha-toxin suppression of various antibiotics against Clostridium perfringens.
Main Methods:
- Macrobroth dilution Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) determinations were performed.
- Alpha-toxin activity was measured at antibiotic concentrations equal to the MIC.
- Bacterial killing dynamics and alpha-toxin production kinetics were studied at 10x MIC concentrations.
Main Results:
- Penicillin exhibited similar MIC and MBC values, suggesting bacteriostatic activity, and failed to suppress alpha-toxin production.
- Clindamycin, rifampin, and metronidazole demonstrated rapid bacterial killing and complete alpha-toxin suppression.
- Tetracycline and chloramphenicol suppressed alpha-toxin but were less effective at reducing bacterial viability.
Conclusions:
- Superior efficacy of clindamycin, rifampin, and metronidazole in experimental gas gangrene is partly explained by their rapid bacterial killing and potent alpha-toxin suppression.
- Penicillin's limited bactericidal activity and persistent alpha-toxin production contribute to its lower therapeutic efficacy in this model.