SynthesisThe Journal of antimicrobial chemotherapy2020
Systematic review of mutations associated with resistance to the new and repurposed Mycobacterium tuberculosis drugs bedaquiline, clofazimine, linezolid, delamanid and pretomanid.
Synthesis in The Journal of antimicrobial chemotherapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 4 of them syntheses that pooled it.
What it found
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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.
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.
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Who cites it
118 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Updates on the Treatment of Drug-Susceptible and Drug-Resistant Tuberculosis: An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline.American journal of respiratory and critical care medicine · 2025Guideline
- Opportunities and limitations of genomics for diagnosing bedaquiline-resistant tuberculosis: a systematic review and individual isolate meta-analysis.The Lancet. Microbe · 2024Pooled it
- Delamanid-containing regimens and multidrug-resistant tuberculosis: A systematic review and meta-analysis.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2022Pooled it
- Genetic variants and their association with phenotypic resistance to bedaquiline inThe Lancet. Microbe · 2021Pooled it
- Synthesis and evaluation of novel 3,5-dinitrobenzoyl substituted amino acid hydrazides againstRSC medicinal chemistry · 2026Article
- No phenotypic resistance observed for most group-3 and -4 variants inMicrobiology spectrum · 2026Article
- Rapid detection of treatment-emergent resistance to bedaquiline and pretomanid inMicrobiology spectrum · 2026Article
- Resistance to Linezolid and Pretomanid in the Era of Modern Drug-Resistant Tuberculosis Treatment in South Africa: A Systematic Review and Meta-Analysis.Antibiotics (Basel, Switzerland) · 2026Review
- Bedaquiline Resistance in Drug-Resistant Tuberculosis in South Africa: A Systematic Review and Meta-Analysis of Emerging Trends.Antibiotics (Basel, Switzerland) · 2026Review
- Whole-Genome Sequencing and Phenotypic Drug Susceptibility Testing of Bedaquilin, Delamanid, Pretomanid, and Linezolid in Drug-ResistantPathogens (Basel, Switzerland) · 2026Article
- A tiled amplicon protocol for culture-free whole-genome sequencing ofJournal of clinical microbiology · 2026Article
- Acquired linezolid resistance in DR-TB: genotype-phenotype discordance and molecular heterogeneity in a retrospective cohort.BMC infectious diseases · 2026Article
- A Short-Course Regimen Containing Delamanid, Bedaquiline and Linezolid for the Treatment of Drug-Resistant Tuberculosis: A Retrospective Study from China.Infection and drug resistance · 2026Article
- The AcasR-FadD9 regulatory axis modulates iron homeostasis and susceptibility to the anti-mycobacterial compound ACA.Frontiers in tuberculosis · 2026Article
- Relapse and Emergent Resistance With Novel Short-Course Regimens for Multidrug-Resistant Tuberculosis, United States, 2022-2024.Open forum infectious diseases · 2026Article
- A Frameshift Mutation in the MethyltransferaseComputational and structural biotechnology journal · 2026Article
- Associating Mycobacterium tuberculosis genomic variants with minimum inhibitory concentrations to delamanid and pretomanid.PloS one · 2026Article
- Tracking the evolution of an extensively drug-resistant cross-borderEuro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin · 2025Article
- Article
- Quality control and considering systematic MIC shifts are key when evaluating the role ofAntimicrobial agents and chemotherapy · 2025Article
58 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
backgroundImproved genetic understanding of Mycobacterium tuberculosis (MTB) resistance to novel and repurposed anti-tubercular agents can aid the development of rapid molecular diagnostics.
methodsAdhering to PRISMA guidelines, in March 2018, we performed a systematic review of studies implicating mutations in resistance through sequencing and phenotyping before and/or after spontaneous resistance evolution, as well as allelic exchange experiments. We focused on the novel drugs bedaquiline, delamanid, pretomanid and the repurposed drugs clofazimine and linezolid. A database of 1373 diverse control MTB whole genomes, isolated from patients not exposed to these drugs, was used to further assess genotype-phenotype associations.
resultsOf 2112 papers, 54 met the inclusion criteria. These studies characterized 277 mutations in the genes atpE, mmpR, pepQ, Rv1979c, fgd1, fbiABC and ddn and their association with resistance to one or more of the five drugs. The most frequent mutations for bedaquiline, clofazimine, linezolid, delamanid and pretomanid resistance were atpE A63P, mmpR frameshifts at nucleotides 192-198, rplC C154R, ddn W88* and ddn S11*, respectively. Frameshifts in the mmpR homopolymer region nucleotides 192-198 were identified in 52/1373 (4%) of the control isolates without prior exposure to bedaquiline or clofazimine. Of isolates resistant to one or more of the five drugs, 59/519 (11%) lacked a mutation explaining phenotypic resistance.
conclusionsThis systematic review supports the use of molecular methods for linezolid resistance detection. Resistance mechanisms involving non-essential genes show a diversity of mutations that will challenge molecular diagnosis of bedaquiline and nitroimidazole resistance. Combined phenotypic and genotypic surveillance is needed for these drugs in the short term.
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