ArticleJournal of clinical microbiology2014
Mixed Mycobacterium tuberculosis complex infections and false-negative results for rifampin resistance by GeneXpert MTB/RIF are associated with poor clinical outcomes.
Article in Journal of clinical microbiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 5 of them syntheses that pooled it.
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Who cites it
83 citing papers in PubMed, 5 syntheses or guidelines pooled it, 145 citations in OpenAlex.
- Pretreatment attrition after rifampicin-resistant tuberculosis diagnosis with Xpert MTB/RIF or ultra in high TB burden countries: a systematic review and meta-analysis.BMJ global health · 2025Pooled it
- Mycobacterium tuberculosis mixed infections and drug resistance in sub-Saharan Africa: a systematic review.African health sciences · 2022Pooled it
- Methods for Detecting Mycobacterial Mixed Strain Infections-A Systematic Review.Frontiers in genetics · 2020Pooled it
- Xpert MTB/RIF assay for the diagnosis of rifampicin resistance in different regions: a meta-analysis.BMC microbiology · 2019Pooled it
- Xpert MTB/RIF and Xpert MTB/RIF Ultra for pulmonary tuberculosis and rifampicin resistance in adults.The Cochrane database of systematic reviews · 2019Pooled it
- Targeted next-generation sequencing of sputum for diagnosis of drug-resistant TB: results of a national survey in Democratic Republic of the Congo.Scientific reports · 2020Trial
- Evaluation of Xpert MTB/RIF assay accuracy for diagnosing TB and detecting rifampin resistance in patients with very low bacterial loads results: a retrospective study in Hunan, China.BMC infectious diseases · 2026Article
- Heteroresistance inFrontiers in cellular and infection microbiology · 2026Review
- Mixed infections and heteroresistance ofEmerging microbes & infections · 2025Article
- Clinical and bacterial determinants of unfavorable tuberculosis treatment outcomes: an observational study in Georgia.Genome medicine · 2025Observational
- Characterization of Drug Resistance Mutations inMicroorganisms · 2025Article
- Ecology, global diversity and evolutionary mechanisms in the Mycobacterium tuberculosis complex.Nature reviews. Microbiology · 2025Review
- The Usefulness of the BD MAX MDR-TB Molecular Test in the Rapid Diagnosis of Multidrug-Resistant Tuberculosis.Pathogens (Basel, Switzerland) · 2025Article
- Investigation of bedaquiline heteroresistance amongMicrobiology spectrum · 2025Article
- Speeding up drug susceptibility testing in Mycobacterium tuberculosis using RNA biomarkers.EBioMedicine · 2025Article
- Signatures of transmission in within-host Mycobacterium tuberculosis complex variation: a retrospective genomic epidemiology study.The Lancet. Microbe · 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
- Assessing the propensity of TB clinical isolates to form viable but non-replicating subpopulations.Scientific reports · 2024Article
- Multi-drug resistant gene mutation analysis inIranian journal of microbiology · 2024Article
- Multi-centric evaluation of Truenat MTB and MTB-RIF Dx assays for diagnosis of extrapulmonary tuberculosis.Scientific reports · 2024Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
Abstract
The Xpert MTB/RIF (Xpert) assay is becoming a principal screening tool for diagnosing rifampin-resistant Mycobacterium tuberculosis complex (MTBC) infection. However, little is known about the performance of the Xpert assay in infections with both drug-sensitive and drug-resistant strains (mixed MTBC infections). We assessed the performance of the Xpert assay for detecting rifampin resistance using phenotypic drug sensitivity testing (DST) as the reference standard in 370 patients with microbiologically proven pulmonary tuberculosis. Mixed MTBC infections were identified genetically through 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) analysis. Logistic regression was used to identify the factors associated with poor (defined as treatment failure, default, and death from any cause) or good (defined as cure or successful treatment completion) clinical outcomes. The analytic sensitivity of the Xpert assay for detecting rifampin resistance was assessed in vitro by testing cultures containing different ratios of drug-sensitive and drug-resistant organisms. Rifampin resistance was detected by the Xpert assay in 52 (14.1%) and by phenotypic DST in 55 (14.9%) patients. Mixed MTBC infections were identified in 37 (10.0%) patients. The Xpert assay was 92.7% (95% confidence interval [CI], 82.4% to 97.9%) sensitive for detecting rifampin resistance and 99.7% (95% CI, 98.3% to 99.9%) specific. When restricted to patients with mixed MTBC infections, Xpert sensitivity was 80.0% (95% CI, 56.3 to 94.3%). False-negative Xpert results (adjusted odds ratio [aOR], 6.6; 95% CI,1.2 to 48.2) and mixed MTBC infections (aOR, 6.5; 95% CI, 2.1 to 20.5) were strongly associated with poor clinical outcome. The Xpert assay failed to detect rifampin resistance in vitro when <90% of the organisms in the sample were rifampin resistant. Our study indicates that the Xpert assay has an increased false-negative rate for detecting rifampin resistance with mixed MTBC infections. In hyperendemic settings where mixed infections are common, the Xpert results might need further confirmation.
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