ArticleAntimicrobial agents and chemotherapy2012
Mycobacterium tuberculosis population structure determines the outcome of genetics-based second-line drug resistance testing.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Pooled it
- Analysis of Drug Resistance Characteristics and Risk Factors of Cavitary Tuberculosis Based on Whole Genome Sequencing and Machine Learning.Open forum infectious diseases · 2026Article
- The potential of molecular testing and mutation analysis for detecting isoniazid and rifampicin-resistant Mycobacterium tuberculosis in Thailand.Revista do Instituto de Medicina Tropical de Sao Paulo · 2026Article
- Diagnostic Accuracy of LiquidArray MTB-XDR VER 1.0 for the Detection of Mycobacterium tuberculosis Complex, Fluoroquinolone, Amikacin, Ethambutol, and Linezolid Susceptibility.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Article
- Population structure and emergence of resistance to new and repurposed drugs in XDR-TB: insights from a 10-year genomic study in the Western Cape, South Africa review.Frontiers in cellular and infection microbiology · 2025Article
- Evaluation of T-NGS, Xpert Ultra, and Line Probe Assay on Clinical Samples for the Diagnosis of Drug-Resistant Pulmonary Tuberculosis in Rio de Janeiro.Revista da Sociedade Brasileira de Medicina Tropical · 2025Article
- Diagnostic accuracy of LiquidArray MTB-XDR VER1.0 for the detection ofResearch square · 2024Article
- Effect of mixed Mycobacterium tuberculosis infection on rapid molecular diagnostics among patients starting MDR-TB treatment in Uganda.BMC infectious diseases · 2024Article
- Effect of mixed Mycobacterium tuberculosis infection on rapid molecular diagnostics among patients starting MDR-TB treatment in Uganda.Research square · 2023Article
- Mortality from drug-resistant tuberculosis in high-burden countries comparing routine drug susceptibility testing with whole-genome sequencing: a multicentre cohort study.The Lancet. Microbe · 2021Article
- Resistance-Conferring Mutations on Whole-Genome Sequencing of Fluoroquinolone-resistant and -Susceptible Mycobacterium tuberculosis Isolates: A Proposed Threshold for Identifying Resistance.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Article
- Evaluation of Anyplex™ II MTB/MDR kit's performance to rapidly detect isoniazid and rifampicin resistant Mycobacterium tuberculosis from various clinical specimens.Molecular biology reports · 2020Article
- Whole genome sequencing of Mycobacterium tuberculosis: current standards and open issues.Nature reviews. Microbiology · 2019Review
- Fluoroquinolone heteroresistance in Mycobacterium tuberculosis: detection by genotypic and phenotypic assays in experimentally mixed populations.Scientific reports · 2019Article
- Genomic characterization of MDR/XDR-TB in Kazakhstan by a combination of high-throughput methods predominantly shows the ongoing transmission of L2/Beijing 94-32 central Asian/Russian clusters.BMC infectious diseases · 2019Article
- Deciphering Within-Host Microevolution ofMicrobiology and molecular biology reviews : MMBR · 2019Review
- Whole-Genome Sequencing for Drug Resistance Profile Prediction inAntimicrobial agents and chemotherapy · 2019Article
- Mycobacterium tuberculosis Subculture Results in Loss of Potentially Clinically Relevant Heteroresistance.Antimicrobial agents and chemotherapy · 2017Article
- Cryptic Microheteroresistance Explains Mycobacterium tuberculosis Phenotypic Resistance.American journal of respiratory and critical care medicine · 2017Article
- Genomic Analysis of the Evolution of Fluoroquinolone Resistance in Mycobacterium tuberculosis Prior to Tuberculosis Diagnosis.Antimicrobial agents and chemotherapy · 2016Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
The global emergence of multidrug-resistant tuberculosis has highlighted the need for the development of rapid tests to identify resistance to second-line antituberculosis drugs. Resistance to fluoroquinolones and aminoglycosides develops through nonsynonymous single nucleotide polymorphisms in the gyrA and gyrB genes and the rrs gene, respectively. Using DNA sequencing as the gold standard for the detection of mutations conferring resistance, in conjunction with spoligotyping, we demonstrated heteroresistance in 25% and 16.3% of Mycobacterium tuberculosis isolates resistant to ofloxacin and amikacin, respectively. Characterization of follow-up isolates from the same patients showed that the population structure of clones may change during treatment, suggesting different phases in the emergence of resistance. The presence of underlying mutant clones was identified in isolates which failed to show a correlation between phenotypic resistance and mutation in the gyrA or rrs gene. These clones harbored previously described mutations in either the gyrA or rrs gene, suggesting that rare mutations conferring resistance to ofloxacin or amikacin may not be as important as was previously thought. We concluded that the absence of a correlation between genotypic and phenotypic resistance implies an early phase in the emergence of resistance within the patient. Thus, the diagnostic utility of genetics-based drug susceptibility tests will depend on the proportion of patients whose bacilli are in the process of acquiring resistance in the study setting. These data have implications for the interpretation of molecular and microbiological diagnostic tests for patients with drug-susceptible and drug-resistant tuberculosis who fail to respond to treatment and for those with discordant results.
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