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Efficacy and Safety of Metronidazole for Pulmonary Multidrug-Resistant Tuberculosis

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Název: Efficacy and Safety of Metronidazole for Pulmonary Multidrug-Resistant Tuberculosis
Autoři: Cheon Tae Kim, Véronique Dartois, Wenjuan Gu, Myungsun Lee, Sang Nae Cho, Clifton E. Barry, So-Young Lee, Ray Y. Chen, Sung Joong Lee, Laura E. Via, Jong Doo Lee, Nadeem Zia, Seung Kyu Park, Doosoo Jeon, Yeon Joo Jeong, Boyoung Jin, Young Ran Kim, Lori E. Dodd, Taegwon Oh, Seokyong Eum, James M. Mountz, Jongmin Lee, Ying Cai, Matthew W. Carroll, Lisa C. Goldfeder
Přispěvatelé: Matthew W. Carroll, Doosoo Jeon, James M. Mountz, Jong Doo Lee, Yeon Joo Jeong, Nadeem Zia, Myungsun Lee, Jongseok Lee, Laura E. Via, Soyoung Lee, Seok-Yong Eum, Sung-Joong Lee, Lisa C. Goldfeder, Ying Cai, Boyoung Jin, Youngran Kim, Taegwon Oh, Ray Y. Chen, Lori E. Dodd, Wenjuan Gu, Veronique Dartois, Seung-Kyu Park, Cheon Tae Kim, Clifton E. Barry III, Sang-Nae Cho, Oh, Tae Gwon, Lee, Jong Doo, Cho, Sang Nae
Zdroj: Antimicrobial Agents and Chemotherapy. 57:3903-3909
Informace o vydavateli: American Society for Microbiology, 2013.
Rok vydání: 2013
Témata: Adult, Male, 0301 basic medicine, Peripheral Nervous System Diseases/chemically induced, Antitubercular Agents/adverse effects, Lung/pathology, Mycobacterium tuberculosis/isolation & purification, Multidrug-Resistant/drug therapy, Antitubercular Agents, Sputum/microbiology, Severity of Illness Index, Metronidazole/administration & dosage, Young Adult, 03 medical and health sciences, Double-Blind Method, Metronidazole, Tuberculosis, Multidrug-Resistant, Confidence Intervals, Tuberculosis, Humans, Metronidazole/therapeutic use, Lung, 0303 health sciences, Metronidazole/pharmacokinetics, Antitubercular Agents/pharmacokinetics, Sputum, Peripheral Nervous System Diseases, Metronidazole/adverse effects, Mycobacterium tuberculosis, 3. Good health, Treatment Outcome, Area Under Curve, Lung/microbiology, Female, Antitubercular Agents/administration & dosage, Antitubercular Agents/therapeutic use
Popis: 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 ( P = 0.04) and liquid culture ( P = 0.04) 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.
Druh dokumentu: Article
Jazyk: English
ISSN: 1098-6596
0066-4804
DOI: 10.1128/aac.00753-13
Přístupová URL adresa: https://aac.asm.org/content/aac/57/8/3903.full.pdf
https://pubmed.ncbi.nlm.nih.gov/23733467
https://aac.asm.org/content/57/8/3903
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3719751/
https://www.ncbi.nlm.nih.gov/pubmed/23733467
https://pubmed.ncbi.nlm.nih.gov/23733467/
https://europepmc.org/abstract/MED/23733467
Rights: ASM Journals Non-Commercial TDM
CC BY NC ND
Přístupové číslo: edsair.doi.dedup.....7dbfc7dde0ff00531213300e21315d8d
Databáze: OpenAIRE
Popis
Abstrakt: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 ( P = 0.04) and liquid culture ( P = 0.04) 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.
ISSN:10986596
00664804
DOI:10.1128/aac.00753-13