Evidence map›Paper›PMID 29459669›Full record

ArticleScientific reports2018

Isoniazid resistance levels of Mycobacterium tuberculosis can largely be predicted by high-confidence resistance-conferring mutations.

Pauline Lempens, Conor J Meehan, Koen Vandelannoote, Kristina Fissette, Pim de Rijk, Armand Van Deun, Leen Rigouts, Bouke C de Jong

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 2 pooled it
7.1field-weighted citation impact, top 2% 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

85 citing papers in PubMed, 2 syntheses or guidelines pooled it, 124 citations in OpenAlex.

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  8. Predicting isoniazid resistance inJournal of clinical microbiology · 2026
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25 more citing papers are in PubMed but not listed here.

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

8 authors at 2 institutions in 1 country.

Pauline LempensUnit of Mycobacteriology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. plempens@itg.be.
Conor J MeehanUnit of Mycobacteriology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
Koen VandelannooteUnit of Mycobacteriology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
Kristina FissetteUnit of Mycobacteriology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
Pim de RijkUnit of Mycobacteriology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
Armand Van DeunUnit of Mycobacteriology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
Leen RigoutsUnit of Mycobacteriology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
Bouke C de JongUnit of Mycobacteriology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
Instituut voor Tropische Geneeskunde · BEUniversity of Antwerp · BE

Funding

European Research Council 311725
6 · The paper itself

Abstract

The majority of Mycobacterium tuberculosis isolates resistant to isoniazid harbour a mutation in katG. Since these mutations cause a wide range of minimum inhibitory concentrations (MICs), largely below the serum level reached with higher dosing (15 mg/L upon 15-20 mg/kg), the drug might still remain partly active in presence of a katG mutation. We therefore investigated which genetic mutations predict the level of phenotypic isoniazid resistance in clinical M. tuberculosis isolates. To this end, the association between known and unknown isoniazid resistance-conferring mutations in whole genome sequences, and the isoniazid MICs of 176 isolates was examined. We found mostly moderate-level resistance characterized by a mode of 6.4 mg/L for the very common katG Ser315Thr mutation, and always very high MICs (≥19.2 mg/L) for the combination of katG Ser315Thr and inhA c-15t. Contrary to common belief, isolates harbouring inhA c-15t alone, partly also showed moderate-level resistance, particularly when combined with inhA Ser94Ala. No overt association between low-confidence or unknown mutations, except in katG, and isoniazid resistance (level) was found. Except for the rare katG deletion, line probe assay is thus not sufficiently accurate to predict the level of isoniazid resistance for a single mutation in katG or inhA.

Indexed as

Drug Resistance, BacterialMutationAntitubercular AgentsBacterial ProteinsCatalaseHumansIsoniazidMicrobial Sensitivity TestsMycobacterium tuberculosisOxidoreductasesTuberculosisAntitubercular AgentsBacterial ProteinsCatalaseInhA protein, MycobacteriumIsoniazidkatG protein, Mycobacterium tuberculosisOxidoreductases

Identifiers

PMID29459669
PMCPMC5818527
OpenAlexW2794372577

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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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.