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Antimicrobial Agents and Chemotherapy, May 1999, p. 1285-1288, Vol. 43, No. 5
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Metronidazole Therapy in Mice Infected with
Tuberculosis
Jason V.
Brooks,
Synthia K.
Furney, and
Ian M.
Orme*
Mycobacteria Research Laboratories,
Department of Microbiology, Colorado State University, Fort
Collins, Colorado 80523
Received 6 April 1998/Returned for modification 22 July
1998/Accepted 27 February 1999
The capacity of metronidazole to inhibit the growth of
Mycobacterium tuberculosis was tested in in vitro and in
vivo mouse models. In vitro addition of metronidazole to cultures of
infected bone marrow-derived macrophages had no effect, nor did it
increase the reduction in bacterial load due to isoniazid. In vivo,
metronidazole did not reduce bacterial numbers in the lungs of
aerosol-infected mice during the active stage of the disease, during a
phase of containment, or after prolonged isoniazid therapy (Cornell
model). A small but significant reduction was seen if metronidazole
therapy was given during an established chronic disease state 100 days after aerosol administration. These data indicate that under most conditions M. tuberculosis organisms are not in a metabolic
state in which they are susceptible to the action of metronidazole and, hence, that this drug would be of limited clinical value.
*
Corresponding author. Mailing address: Department of
Microbiology, Colorado State University, Fort Collins, CO 80523. Phone: (970) 491-5777. Fax: (970) 491-5125. E-mail:
iorme{at}lamar.colostate.edu.
Antimicrobial Agents and Chemotherapy, May 1999, p. 1285-1288, Vol. 43, No. 5
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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