ArticleThe Journal of antimicrobial chemotherapy2022
Ancient and recent differences in the intrinsic susceptibility of Mycobacterium tuberculosis complex to pretomanid.
Article in The Journal of antimicrobial chemotherapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 64 citations in OpenAlex.
- Bedaquiline-Pretomanid-Linezolid Regimens for Drug-Resistant Tuberculosis.The New England journal of medicine · 2022Trial
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- Future-proofing tuberculosis therapy: framework for concurrent drug and resistance testing development.The Lancet. Infectious diseases · 2026Review
- Reference-free clustering as an epidemiological tool forMicrobial genomics · 2026Article
- Exploiting DprE2 pathway redundancy to enhance potency and overcome resistance to pretomanid in Mycobacterium tuberculosis.npj antimicrobials and resistance · 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
- Integrating chemical, genetic, and feasibility assessments for anti-tubercular target validation.EMBO molecular medicine · 2026Review
- Article
- High efficacy of BPaL among patients infected withIJTLD open · 2026Article
- Whole-Genome Sequencing and Phenotypic Drug Susceptibility Testing of Bedaquilin, Delamanid, Pretomanid, and Linezolid in Drug-ResistantPathogens (Basel, Switzerland) · 2026Article
- Associating Mycobacterium tuberculosis genomic variants with minimum inhibitory concentrations to delamanid and pretomanid.PloS one · 2026Article
- Mycobacterium tuberculosis biology, pathogenicity and interaction with the host.Nature reviews. Microbiology · 2025Review
- Pretomanid for the treatment of drug resistant pulmonary tuberculosis: a comprehensive review.Archives of microbiology · 2025Review
- Article
- Mycobacterium tuberculosis complex Lineage 1: A neglected cause of tuberculosis.PLoS neglected tropical diseases · 2025Review
- Ecology, global diversity and evolutionary mechanisms in the Mycobacterium tuberculosis complex.Nature reviews. Microbiology · 2025Review
- Engineered Mycobacteriophage TM4::GeNL Rapidly Determines Bedaquiline, Pretomanid, Linezolid, Rifampicin, and Clofazimine Sensitivity in Mycobacterium tuberculosis Clinical Isolates.The Journal of infectious diseases · 2025Article
- Performance of a broth microdilution assay for routine minimum inhibitory concentration determination of 14 anti-tuberculous drugs against theAntimicrobial agents and chemotherapy · 2025Article
- Identification of bacterial determinants of tuberculosis infection and treatment outcomes: a phenogenomic analysis of clinical strains.The Lancet. Microbe · 2024Article
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Authors and funding
27 authors at 12 institutions in 9 countries.
Funding
Abstract
objectivesTo develop a robust phenotypic antimicrobial susceptibility testing (AST) method with a correctly set breakpoint for pretomanid (Pa), the most recently approved anti-tuberculosis drug.
methodsThe Becton Dickinson Mycobacterial Growth Indicator Tube™ (MGIT) system was used at six laboratories to determine the MICs of a phylogenetically diverse collection of 356 Mycobacterium tuberculosis complex (MTBC) strains to establish the epidemiological cut-off value for pretomanid. MICs were correlated with WGS data to study the genetic basis of differences in the susceptibility to pretomanid.
resultsWe observed ancient differences in the susceptibility to pretomanid among various members of MTBC. Most notably, lineage 1 of M. tuberculosis, which is estimated to account for 28% of tuberculosis cases globally, was less susceptible than lineages 2, 3, 4 and 7 of M. tuberculosis, resulting in a 99th percentile of 2 mg/L for lineage 1 compared with 0.5 mg/L for the remaining M. tuberculosis lineages. Moreover, we observed that higher MICs (≥8 mg/L), which probably confer resistance, had recently evolved independently in six different M. tuberculosis strains. Unlike the aforementioned ancient differences in susceptibility, these recent differences were likely caused by mutations in the known pretomanid resistance genes.
conclusionsIn light of these findings, the provisional critical concentration of 1 mg/L for MGIT set by EMA must be re-evaluated. More broadly, these findings underline the importance of considering the global diversity of MTBC during clinical development of drugs and when defining breakpoints for AST.
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