Evidence map›Paper›PMID 23733467›Full record

Trial reportAntimicrobial agents and chemotherapy2013

Efficacy and safety of metronidazole for pulmonary multidrug-resistant tuberculosis.

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 and 15 more

Open access · bronzeAbstract readClinical Trial, Phase IIRandomized Controlled Trial
In one paragraph

Trial report in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
6.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.

  1. Treatment Effect Measures for Culture Conversion Endpoints in Phase IIb Tuberculosis Treatment Trials.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021
    Pooled it
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  10. Journal of medical radiation sciences · 2022
    Article
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  14. Metronidazole-associated Neurologic Events: A Nested Case-control Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors at 8 institutions in 2 countries.

Matthew W CarrollTuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
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
Sang-Nae Cho
International Tuberculosis Research Center · KRNational Institutes of Health · USYonsei University · KRMasan National Tuberculosis Hospital · KRNational Institute of Allergy and Infectious Diseases · USUniversity of Pittsburgh · USFrederick National Laboratory for Cancer Research · USPusan National University · KR

Funding

International Research in Korea: Clinical Studies of Drug-Resistant TuberculosisZIAAI001067 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BARRY, CLIFTON · 2009 to 2017
$6.9M
CCR NIH HHS HHSN261200800001CNCI NIH HHS HHSN261200800001E
6 · The paper itself

Abstract

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.

Indexed as

AdultAntitubercular AgentsArea Under CurveConfidence IntervalsDouble-Blind MethodFemaleHumansLungMaleMetronidazoleMycobacterium tuberculosisPeripheral Nervous System DiseasesSeverity of Illness IndexSputumTreatment OutcomeTuberculosis, Multidrug-ResistantAntitubercular AgentsMetronidazole

Identifiers

PMID23733467
PMCPMC3719751
OpenAlexW2127106452

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.