Metronidazole has no antibacterial effect in Cornell model murine tuberculosis.
METHODS
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.


METHODS
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.


CONCLUSIONS
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.
Department of Medical Microbiology, St George's Hospital Medical School, London, UK.
J
J
Dhillon
B W
BW
Allen
Y M
YM
Hu
A R
AR
Coates
D A
DA
Mitchison
D000818:Animals; D002452:Cell Count; D008168:Lung / Q000166:cytology; D008795:Metronidazole / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000187:drug effects*; D015610:Serum Bactericidal Test; D013154:Spleen / Q000166:cytology; D013234:Stem Cells
D008795:Metronidazole