Retrospective Cohort Analysis for Identification of Discordant Rifampicin-resistant Xpert MTB/RIF Assay Results in South Kivu, Eastern Democratic Republic of the Congo, a High Burden Tuberculosis Setting.

Background The Xpert assay has revolutionized the rapid detection of resistance to rifampicin. However, Xpert has its pitfalls. We explored potential determinants of false-positive rifampicin resistance when using Xpert, aiming to refine the precision of tuberculosis diagnostics and subsequently con...

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Detalles Bibliográficos
Publicado en:Clinical Infectious Diseases Vol. 82; no. 2; pp. 274 - 282
Autores principales: Bisimwa, Bertin C, Kiselinova, Maja, Cuella-Martin, Isabel, Rigouts, Leen, Bulabula, André N H, Byela, Valéry, Chirambiza, Jean-Paul, Mulume, Eric, Birembano, Freddy, Katoto, Patrick D M C
Formato: research tables/charts Journal Article
Publicado: Oxford University Press / USA 2/15/2026
Acceso en línea:Ver este registro en EBSCOhost
Descripción
Sumario:Background The Xpert assay has revolutionized the rapid detection of resistance to rifampicin. However, Xpert has its pitfalls. We explored potential determinants of false-positive rifampicin resistance when using Xpert, aiming to refine the precision of tuberculosis diagnostics and subsequently contribute to better patient outcomes. Methods This is a retrospective cross-sectional analysis of archived Xpert files from the South Kivu province, used to diagnose Mycobacterium tuberculosis (MTB) between 2013 and 2018. Xpert cycle threshold was extracted for each molecular beacon probe, and Δ Ct was calculated. We used the MTBDR plus line-probe assay, which covers the same 81-bp RRDR, as a reference test. Results Of 1900 samples positive for MTB, 220 (11.2%) were rifampicin resistant. Of the 141 patients' sputum samples that had results for both Xpert and MTBDR plus , 45 (31.9%) showed discordant results with Xpert, indicating rifampicin resistance while MTBDR plus indicated rifampicin susceptibility, suggesting false-positive rifampicin resistance detection by Xpert, predominantly in samples with very low (Ct > 28, odds ratio [OR] = 2.23, 95% CI: 1.30–3.82) or low (Ct 22–28, OR = 1.81, 95% CI: 1.21–2.71) bacterial loads. Probe E was the most frequently missed probe, followed by multiple probe dropouts or absence of probe binding (OR = 1.5, 95% CI:.731–3.076). Conclusions Our findings indicate that low and very low MTB bacterial loads in sputum are strongly associated with discordant rifampicin resistance results when using Xpert. Further research into underlying mechanisms is needed to establish causality definitively.