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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Efficacy and safety of metronidazole for pulmonary multidrug-resistant tuberculosis
Antimicrobial Agents and Chemotherapy, Volume 57, No. 8, Year 2013
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Description
Pulmonary lesions from active tuberculosis patients are thought to contain persistent, nonreplicating bacilli that arise from hypoxic stress. Metronidazole, approved for anaerobic infections, has antituberculosis activity against anoxic bacilli in vitro and in some animal models and may target persistent, nonreplicating bacilli. In this double-blind, placebo-controlled trial, pulmonary multidrug-resistant tuberculosis subjects were randomly assigned to receive metronidazole (500 mg thrice daily) or placebo for 8 weeks in addition to an individualized background regimen. Outcomes were measured radiologically (change on high-resolution computed tomography [HRCT]), microbiologically (time to sputum smear and culture conversion), and clinically (status 6 months after stopping therapy). Enrollment was stopped early due to excessive peripheral neuropathies in the metronidazole arm. Among 35 randomized subjects, 31 (15 metronidazole, 16 placebo) were included in the modified intent-to-treat analysis. There were no significant differences by arm in improvement of HRCT lesions from baseline to 2 or 6 months. More subjects in the metronidazole arm converted their sputum smear (P0.04) and liquid culture (P0.04) to negative at 1 month, but these differences were lost by 2 months. Overall, 81% showed clinical success 6 months after stopping therapy, with no differences by arm. However, 8/16 (50%) of subjects in the metronidazole group and 2/17 (12%) of those in the placebo group developed peripheral neuropathy. Subjects who received metronidazole were 4.3-fold (95% confidence interval [CI], 1.1 to 17.1) more likely to develop peripheral neuropathies than subjects who received placebo. Metronidazole may have increased early sputum smear and culture conversion but was too neurotoxic to use over the longer term. Newer nitroimidazoles with both aerobic and anaerobic activity, now in clinical trials, may increase the sterilizing potency of future treatment regimens. © 2013, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Carroll, Matthew W.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Jeon, Doosoo
South Korea, Changwon
National Masan Hospital
Mountz, James Michael
United States, Pittsburgh
University of Pittsburgh
Lee, Jong-doo
South Korea, Seoul
Yonsei University College of Medicine
Jeong, Yeon-joo
South Korea, Yangsan
Medical School of Pusan National University
Zia, Nadeem
United States, Pittsburgh
University of Pittsburgh
Lee, Myungsun
South Korea, Changwon
International Tuberculosis Research Center
Lee, Jongseok
South Korea, Changwon
International Tuberculosis Research Center
Via, L. E.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Lee, Soyoung
South Korea, Changwon
International Tuberculosis Research Center
Eum, Seokyong
South Korea, Changwon
International Tuberculosis Research Center
Lee, Sung-joong
South Korea, Changwon
International Tuberculosis Research Center
Goldfeder, Lisa C.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Cai, Ying
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Kim, Youngran
South Korea, Changwon
International Tuberculosis Research Center
Chen, Ray Y.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Dodd, Lori Elizabeth
United States, Bethesda
National Institutes of Health Nih
Gu, Wenjuan
United States, Reston
Leidos Inc.
Dartois, Véronique A.
United States, Newark
Public Health Research Institute
Park, Seungkyu
South Korea, Changwon
National Masan Hospital
Barry, Clifton Earl
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Statistics
Citations: 66
Authors: 21
Affiliations: 9
Identifiers
Doi:
10.1128/AAC.00753-13
ISSN:
10986596
Research Areas
Disability