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Metronidazole has no antibacterial effect in Cornell model murine tuberculosis
1Department of Medical Microbiology, St George's Hospital Medical School, London, UK.
Setting:
Experiments in vitro on the bactericidal activity of metronidazole and in the Cornell model of murine tuberculosis.
Objective:
To assess the sterilising activity of maximal metronidazole dosage and its activity against bacilli held dormant by immunity in the mouse.
Design:
In vitro experiments showed that metronidazole was only bactericidal at attainable concentrations (50-100 microg/ml) under anaerobic conditions. In the Cornell model, isoniazid 25 mg/kg and high dosage pyrazinamide 1000 mg/kg was given in the diet with and without 1500 mg/kg metronidazole for the initial 14 weeks of sterilising chemotherapy. In the subsequent sterile state, metronidazole at 0, 100 and 250 mg/kg was given by daily gavage for 6 weeks. Finally, the mice were given 3 weeks of high dosage steroids and their organs were cultured in selective liquid medium.
Results:
Metronidazole had no activity either in the initial sterilising phase or in the subsequent sterile state.
Conclusion:
The O2 tension in the cellular lesions of murine tuberculosis is unlikely to be sufficiently low to allow metronidazole to act. Its activity should be assessed in caseous lesions.
