Performance of the G4 Xpert® MTB/RIF assay for the detection of Mycobacterium tuberculosis and rifampin resistance: a retrospective case-control study of analytical and clinical samples from high- and low-tuberculosis prevalence settings

Abstract

BackgroundThe Xpert® MTB/RIF (Xpert) assay is a rapid PCR-based assay for the detection of Mycobacterium tuberculosis complex DNA (MTBc) and mutations associated with rifampin resistance (RIF). An updated version introduced in 2011, the G4 Xpert, included modifications to probe B and updated analytic software.MethodsAn analytical study was performed to assess Xpert detection of mutations associated with rifampin resistance in rifampin-susceptible and -resistant isolates. A clinical study was performed in which specimens from US and non-US persons suspected of tuberculosis (TB) were tested to determine Xpert performance characteristics. All specimens underwent smear microscopy, mycobacterial culture, conventional drug-susceptibility testing and Xpert testing; DNA from isolates with discordant rifampin resistance results was sequenced.ResultsAmong 191 laboratory-prepared isolates in the analytical study, Xpert sensitivity for detection of rifampin resistance associated mutations was 97.7% and specificity was 90.8%, which increased to 99.0% after DNA sequencing analysis of the discordant samples. Of the 1,096 subjects in the four clinical studies, 49% were from the US. Overall, Xpert detected MTBc in 439 of 468 culture-positive specimens for a sensitivity of 93.8% (95% confidence interval [CI]: 91.2%–95.7%) and did not detect MTBc in 620 of 628 culture-negative specimens for a specificity of 98.7% (95% CI: 97.5%–99.4%). Sensitivity was 99.7% among smear-positive cases, and 76.1% among smear-negative cases. Non-determinate MTBc detection and false-positive RIF resistance results were low (1.2 and 0.9%, respectively).ConclusionsThe updated Xpert assay retained the high sensitivity and specificity of the previous assay versions and demonstrated low rates of non-determinate and RIF resistance false positive results.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-2039-4) contains supplementary material, which is available to authorized users.

Improving tuberculosis management in prisons: Impact of a rapid molecular point-of-care test

“…In TB POC diagnosis raw sputa must be used. in the first part of our study, we demonstrated that the performances of Xpert on raw and decontaminated sputum are similar as already published [19], and that implementation of this NAAT in prison hospitals should be considered. In the second part of our study, three volunteer physicians at the prison hospital were trained.…”

Xpert^®MTB/RIF para el diagnóstico de tuberculosis en condiciones programáticas en una región de alta endemicidad en México

“…La versión del cartucho (G1, G2, G3, G4) no parece afectar la sensibilidad o especificidad de los resultados. [4][5][6] Sin embargo, estos valores de sensibilidad deben ser tomados con reserva ya que los métodos fenotípicos no constituyen un adecuado estándar de oro para determinar la sensibilidad del Xpert  MTB/RIF. Un metaanálisis que incluyó 10 estudios con 1,381 cepas reportó una sensibilidad analítica para detección de MTB mediante el cultivo MGIT de 81.5 y 67% para el cultivo sólido de Lowenstein-Jensen, 7 por lo que seguramente los valores de sensibilidad del Xpert  MTB/ RIF son superiores a lo actualmente reportado utilizando al cultivo como estándar de referencia.…”

GeneXpert: a game changer in the detection and diagnosis of childhood tuberculosis

“…GeneXpert assay is more sensitive than direct smear but as accurate as culture with less turanaround time. [13][14][15][16][17][18][19] The focus of these studies were on pulmonary tuberculosis while there is limited data on the diagnostic utility of extrapulmonary tuberculosis. [20][21][22][23][24][25][26][27] Studies of diagnostic utility of geneXpert study in the pediatric population is limited, more so from Indian population.…”