Management of false-positive rifampicin resistant Xpert MTB/RIF

We read the study by Jean Claude Semuto Ngabonziza and colleagues1Ngaboninza JCS Decroo T Migambi P et al.Prevalence and drivers of false-positive rifampicin-resistant Xpert MTB/RIF results: a prospective observational study in Rwanda.Lancet Microbe. 2020; 1: e74-e83Summary Full Text Full Text PDF Scopus (15) Google Scholar in The Lancet Microbe, in which the authors identified an association between false-positive rifampicin-resistant Xpert MTB/RIF (Xpert; G4 cartridge; Cepheid, Sunnyvale, CA, USA) results and a very low bacillary load.1Ngaboninza JCS Decroo T Migambi P et al.Prevalence and drivers of false-positive rifampicin-resistant Xpert MTB/RIF results: a prospective observational study in Rwanda.Lancet Microbe. 2020; 1: e74-e83Summary Full Text Full Text PDF Scopus (15) Google Scholar This association has previously been described,2Ocheretina O Byrt E Mabou M-M et al.False-positive rifampin resistant results with Xpert MTB/RIF version 4 assay in clinical samples with a low bacterial load.Diagn Microbiol Infect Dis. 2016; 85: 53-55Crossref PubMed Scopus (46) Google Scholar, 3Sahrin M Rahman A Uddin MKM et al.Discordance in XpertR MTB/RIF assay results among low bacterial load clinical specimens in Bangladesh.Int J Tuberc Lung Dis. 2018; 22: 1056-1062Crossref PubMed Scopus (10) Google Scholar, 4Huo F Ma Yifeng Liu R et al.Interpretation of discordant rifampicin susceptibility test results obtained using GeneXpert vs phenotypic drug susceptibility testing.Open Forum Infect Dis. 2020; 7: 1-7Crossref Scopus (9) Google Scholar and Xpert rifampicin-resistant results associated with a very low bacillary load were recommended to be confirmed by testing a second specimen. Ngaboninza and colleagues1Ngaboninza JCS Decroo T Migambi P et al.Prevalence and drivers of false-positive rifampicin-resistant Xpert MTB/RIF results: a prospective observational study in Rwanda.Lancet Microbe. 2020; 1: e74-e83Summary Full Text Full Text PDF Scopus (15) Google Scholar suggested that these patients should be managed with a drug susceptible tuberculosis regimen until confirmatory results are available. We did a study in Western Cape, South Africa between Jan 1, 2015, and Nov 30, 2016, describing discordance regarding rifampicin between results from Xpert (G4) and GenoType MTBDRplus lineprobe assay (Hain Lifesciences, Nehren, Germany). We found that a very low bacillary load measured by Xpert was associated with false rifampicin resistance.5Ghebrekristos Y Characterization of Mycobacterium tuberculosis isolates with discordant rifampicin susceptibility test results. University of Cape Town, 2018: 69Google Scholar Compared with the study by Ngaboninza and colleagues,1Ngaboninza JCS Decroo T Migambi P et al.Prevalence and drivers of false-positive rifampicin-resistant Xpert MTB/RIF results: a prospective observational study in Rwanda.Lancet Microbe. 2020; 1: e74-e83Summary Full Text Full Text PDF Scopus (15) Google Scholar in which a very low bacillary load was found to be present in 61% of samples tested with Xpert, we found that only 16% of all Xpert tests with rifampicin resistance had a very low bacillary load. In addition, of the 239 specimens with a very low bacillary load, only 47 (19·6%; 95% CI 15·1–25·2%) were confirmed as false rifampicin resistant by sequencing the rifampicin-resistance determining region of the rpoB gene.5Ghebrekristos Y Characterization of Mycobacterium tuberculosis isolates with discordant rifampicin susceptibility test results. University of Cape Town, 2018: 69Google Scholar Therefore, we agree with Ngaboninza and colleagues that a rifampicin-resistant Xpert result associated with a very low bacillary load requires confirmation by testing another specimen. However, in our setting we would not recommend managing these patients with a drug-susceptible tuberculosis regimen because 80% of patients have rifampicin-resistant tuberculosis. Recommendations for patient management should be setting-specific and based on local evidence. We declare no competing interests. Prevalence and drivers of false-positive rifampicin-resistant Xpert MTB/RIF results: a prospective observational study in RwandaThe Xpert testing algorithm should include an assessment of bacillary load and retesting in case rifampicin resistance is detected on a paucibacillary sputum sample. Only when rifampicin resistance has been confirmed on repeat testing should multidrug-resistant tuberculosis treatment be started. When rifampicin resistance has not been confirmed on repeat testing, we propose that patients should be given first-line anti-tuberculosis drugs and monitored closely during treatment, including by baseline culture, pDST, and further Xpert testing. Full-Text PDF Open AccessManagement of falsepositive rifampicin resistant Xpert MTB/RIF – Authors' replyWe thank Natalie Beylis and colleagues for highlighting the importance of adapting guidelines on the interpretation of Xpert MTB/RIF (Xpert) rifampicin-resistance results for local settings. The positive predictive value—the proportion of true rifampicin resistance in patients with a very low bacillary load on Xpert—ranged between nine (14%) of 63 patients in Rwanda and 192 (80%) of 239 patients in South Africa.1 The positive predictive value is strongly correlated with the pretest probability, which depends on the prevalence of rifampicin resistance (lower in Rwanda than in South Africa) and indications for Xpert testing. 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