ArticleScientific reports2019
Fluoroquinolone heteroresistance in Mycobacterium tuberculosis: detection by genotypic and phenotypic assays in experimentally mixed populations.
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 34 papers, 3 of them syntheses that pooled it.
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Who cites it
34 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Global trends and research profile of antibiotic heteroresistance: a bibliometric and visual analysis.Frontiers in microbiology · 2026Pooled 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
- Antibiotic heteroresistance in Mycobacterium tuberculosis isolates: a systematic review and meta-analysis.Annals of clinical microbiology and antimicrobials · 2021Pooled it
- Within-host pathogen population diversity predicts treatment response in Tuberculosis.medRxiv : the preprint server for health sciences · 2026Article
- Multiplex fluorescent PCR-based detection of Helicobacter pylori nucleic acid and antibiotic resistance genes in clinical stool samples: a performance evaluation from Gansu Province, China.BMC infectious diseases · 2026Article
- Screening for heterogeneous drug resistance in tuberculosis and its impact on clinical prognosis: A comprehensive review.iScience · 2026Review
- Multicentre field evaluation of Xpert MTB/XDR in sub-Saharan Africa.ERJ open research · 2026Article
- Heteroresistance inFrontiers in cellular and infection microbiology · 2026Review
- Speeding up drug susceptibility testing in Mycobacterium tuberculosis using RNA biomarkers.EBioMedicine · 2025Article
- Genetic Characterization and Population Structure of Drug-ResistantAntibiotics (Basel, Switzerland) · 2024Article
- Impacts of MDR/XDR-TB on the global tuberculosis epidemic: Challenges and opportunities.Current research in microbial sciences · 2024Review
- Rapid Diagnosis of Drug-Resistant Tuberculosis-Opportunities and Challenges.Pathogens (Basel, Switzerland) · 2023Review
- Mixed infections in genotypic drug-resistant Mycobacterium tuberculosis.Scientific reports · 2023Article
- Quantification of Isoniazid-Heteroresistant Mycobacterium tuberculosis Using Droplet Digital PCR.Journal of clinical microbiology · 2023Article
- Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a 2023 TBnet/RESIST-TB consensus statement.The Lancet. Infectious diseases · 2023Review
- Spatial Distribution of Drug-ResistantPathogens (Basel, Switzerland) · 2023Article
- Comparative Study on Tuberculosis Drug Resistance and Molecular Detection Methods Among Different Mycobacterium Tuberculosis Lineages.Infection and drug resistance · 2023Article
- Updating the WHO target product profile for next-generation Mycobacterium tuberculosis drug susceptibility testing at peripheral centres.PLOS global public health · 2023Article
- Development and Assessment of a Novel Whole-Gene-Based Targeted Next-Generation Sequencing Assay for Detecting the Susceptibility of Mycobacterium tuberculosis to 14 Drugs.Microbiology spectrum · 2022Article
- Detection of Mixed Populations of Clarithromycin-Susceptible and -Resistant Mycobacterium abscessus Strains.Journal of clinical microbiology · 2022Article
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heteroresistance - the simultaneous presence of drug-susceptible and -resistant organisms - is common in Mycobacterium tuberculosis. In this study, we aimed to determine the limit of detection (LOD) of genotypic assays to detect gatifloxacin-resistant mutants in experimentally mixed populations. A fluoroquinolone-susceptible M. tuberculosis mother strain (S) and its in vitro selected resistant daughter strain harbouring the D94G mutation in gyrA (R) were mixed at different ratio's. Minimum inhibitory concentrations (MICs) against gatifloxacin were determined, while PCR-based techniques included: line probe assays (Genotype MTBDRsl and GenoScholar-FQ + KM TB II), Sanger sequencing and targeted deep sequencing. Droplet digital PCR was used as molecular reference method. A breakpoint concentration of 0.25 mg/L allows the phenotypic detection of ≥1% resistant bacilli, whereas at 0.5 mg/L ≥ 5% resistant bacilli are detected. Line probe assays detected ≥5% mutants. Sanger sequencing required the presence of around 15% mutant bacilli to be detected as (hetero) resistant, while targeted deep sequencing detected ≤1% mutants. Deep sequencing and phenotypic testing are the most sensitive methods for detection of fluoroquinolone-resistant minority populations, followed by line probe assays (provided that the mutation is confirmed by a mutation band), while Sanger sequencing proved to be the least sensitive method.
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