ArticleScientific reports2019
Variable ability of rapid tests to detect Mycobacterium tuberculosis rpoB mutations conferring phenotypically occult rifampicin resistance.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 56 citations in OpenAlex.
- Genomic insights into low-level rifampicin resistance mediated by borderlineMicrobiology spectrum · 2026Article
- Phenotypic discordance in rifampicin resistance detection amongMicrobiology spectrum · 2026Review
- Targeted Next-Generation Sequencing in Drug-Resistant Tuberculosis: WHO Guidance and Practical Implementation Priorities.Biomedicines · 2026Review
- Beyond Hotspot Mutations: Diagnostic Relevance of High Frequency, Low Frequency, and DisputedPathogens (Basel, Switzerland) · 2025Review
- Variability in intrinsic drug tolerance inAntimicrobial agents and chemotherapy · 2025Article
- Accuracy of SAM-TB Platform as a Diagnostic Assay for Detection of Mycobacterium tuberculosis Drug Resistance Versus TB-Proflier, PhyResSE, and Mykrobe: A Head-to-Head Comparison.Current microbiology · 2025Article
- Engineered Mycobacteriophage TM4::GeNL Rapidly Determines Bedaquiline, Pretomanid, Linezolid, Rifampicin, and Clofazimine Sensitivity in Mycobacterium tuberculosis Clinical Isolates.The Journal of infectious diseases · 2025Article
- Discordance in genotypic and phenotypic drug susceptibility results: time to reconsider critical concentration of rifampicin.Microbiology spectrum · 2025Article
- Speeding up drug susceptibility testing in Mycobacterium tuberculosis using RNA biomarkers.EBioMedicine · 2025Article
- Drug-resistant tuberculosis: a persistent global health concern.Nature reviews. Microbiology · 2024Review
- Detection of multidrug-resistance in Mycobacterium tuberculosis by phenotype- and molecular-based assays.Annals of clinical microbiology and antimicrobials · 2024Article
- Whole-genome sequencing of clinical isolates from tuberculosis patients in India: real-world data indicates a high proportion of pre-XDR cases.Microbiology spectrum · 2024Article
- Unraveling resistance mechanisms in combination therapy: A comprehensive review of recent advances and future directions.Heliyon · 2024Review
- Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach.Nature communications · 2024Article
- Phenotype versus genotype discordant rifampicin susceptibility testing in tuberculosis: implications for a diagnostic accuracy.Microbiology spectrum · 2024Article
- Effect of mixed Mycobacterium tuberculosis infection on rapid molecular diagnostics among patients starting MDR-TB treatment in Uganda.BMC infectious diseases · 2024Article
- Insights into the in-vitro Susceptibility and Drug-Drug Interaction Profiles Against Drug-Resistant and SusceptibleInfection and drug resistance · 2024Article
- Effects of sputum bacillary load and age on GeneXpert and traditional methods in pulmonary tuberculosis: a 4-year retrospective comparative study.BMC infectious diseases · 2023Article
- Performance of the MeltPro TB assay as initial test for diagnosis of pulmonary tuberculosis with drug-resistance detection.Molecular medicine (Cambridge, Mass.) · 2023Article
- Quantitative measurement of antibiotic resistance inResearch square · 2023Article
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We compared the ability of commercial and non-commercial, phenotypic and genotypic rapid drug susceptibility tests (DSTs) to detect rifampicin resistance (RR)-conferring 'disputed' mutations frequently missed by Mycobacterium Growth Indicator Tube (MGIT), namely L430P, D435Y, L452P, and I491F. Strains with mutation S450L served as positive control while wild-types were used as negative control. Of the 38 mutant strains, 5.7% were classified as RR by MGIT, 16.2% by Trek Sensititre MYCOTB MIC plate, 19.4% by resazurin microtiter plate assay (REMA), 50.0% by nitrate reductase assay (NRA), and 62.2% by microscopic observation direct susceptibility testing (MODS). Reducing MGIT rifampicin concentration to 0.5 µg/ml, and/or increasing incubation time, enhanced detection of disputed mutations from 5.7% to at least 65.7%, particularly for mutation I491F (from 0.0 to 75.0%). Compared with MGIT at standard pre-set time with 0.25 µg/ml ECOFF as breakpoint, we found a statistically significant increase in the ability of MGIT to resolve disputed mutants and WT strains at extended incubation period of 15 and 21 days, with 0.5 µg/ml and 1 µg/ml ECOFF respectively. MODS detected 75.0% of the I491F strains and NRA 62.5%, while it was predictably missed by all molecular assays. Xpert MTB/RIF, Xpert Ultra, and GenoscholarTB-NTM + MDRTB detected all mutations within the 81 bp RR determining region. Only GenoType MTBDRplus version 2 missed mutation L430P in 2 of 11 strains. Phenotypic and genotypic DSTs varied greatly in detecting occult rifampicin resistance. None of these methods detected all disputed mutations without misclassifying wild-type strains.
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