Xpert® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults

Abstract

Background Accurate and rapid detection of tuberculosis (TB) and drug resistance are critical for improving patient care and decreasing the spread of TB. Xpert® MTB/RIF assay (Xpert) is a rapid, automated test that can detect both TB and rifampicin resistance, within two hours after starting the test, with minimal hands-on technical time, but is more expensive than conventional sputum microscopy. Objectives To assess the diagnostic accuracy of Xpert for pulmonary TB (TB detection), both where Xpert was used as an initial test replacing microscopy, and where Xpert was used as an add-on test following a negative smear microscopy result. To assess the diagnostic accuracy of Xpert for rifampicin resistance detection where Xpert was used as the initial test, replacing conventional culture-based drug susceptibility testing. The population of interest was adults suspected of having pulmonary TB or multidrug-resistant TB (MDR-TB), with or without HIV infection. Search methods We performed a comprehensive search of the following databases: Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; ISI Web of Knowledge; MEDION; LILACS; BIOSIS; and SCOPUS. We also searched the metaRegister of Controlled Trials (mRCT) and the search portal of the WHO International Clinical Trials Registry Platform to identify ongoing trials. We performed searches on 25 September 2011 and we repeated them on 15 December 2011, without language restriction. Selection criteria We included randomized controlled trials, cross-sectional, and cohort studies that used respiratory specimens to compare Xpert with culture for detecting TB and Xpert with conventional phenotypic drug susceptibility testing for detecting rifampicin resistance. Data collection and analysis For each study, two review authors independently extracted a set of data using a standardized data extraction form. When possible, we extracted data for subgroups by smear and HIV status. We assessed the quality of studies using the QUADAS-2 tool. We carried out meta-analyses to estimate the pooled sensitivity and specificity of Xpert separately for TB detection and rifampicin resistance detection using a bivariate random-effects model. We estimated the median pooled sensitivity and specificity and their 95% credible intervals (CrI). Main results We identified 18 unique studies as eligible for this review, including two multicentre international studies, one with five and the other with six distinct study centres. The majority of studies (55.6%) were performed in low-income and middle-income countries. In 17 of the 18 studies, Xpert was performed by trained technicians in reference laboratories. When used as an initial test replacing smear microscopy (15 studies, 7517 participants), Xpert achieved a pooled sensitivity of 88% (95% CrI 83% to 92%) and pooled specificity of 98% (9...

Discordance between Xpert MTB/RIF Assay and Bactec MGIT 960 Culture System for Detection of Rifampin-Resistant Mycobacterium tuberculosis Isolates in a Country with a Low Tuberculosis (TB) Incidence

“…The data presented here on 452 samples show that the Xpert assay correctly identified RMP susceptibility in 451 of 452 patients. This is excellent performance, considering that the pooled sensitivity and specificity of the Xpert assay for RMP resistance detection in pulmonary samples have been reported as 95% and 98%, respectively (17). The data also support the high (99%) negative predictive value of the Xpert assay for RMP resistance detection, as suggested by the WHO data for settings with a low prevalence of RMP resistance (10).…”

Point-of-Care System for Detection of Mycobacterium tuberculosis and Rifampin Resistance in Sputum Samples

“…We have shown that the sample extraction process workflow is capable of processing the most purulent portion of sputum (the "core"), and this tended to generate the best PCR amplification profiles in comparison to samples taken from the more fluid peripheral parts of the sputum samples. However, other factors, such as the condition of the specimen (fresh versus frozen) or the specimen preparation (decontamination), were found to alter the performance of the Genedrive system to some degree (data not shown), as has been reported for the GeneXpert system (20). An advantage of the sample processing workflow in the Genedrive instructions for use is the ability to use a small sample volume.…”

Simplified Microarray System for Simultaneously Detecting Rifampin, Isoniazid, Ethambutol, and Streptomycin Resistance Markers in Mycobacterium tuberculosis

“…Since the incidence of genotypic false-positive RIF resistance depends on the prevalence of RIF resistance in a given population (34,35), the unresolved clinical questions are how to accurately correlate genotype with drug susceptibility phenotypes while fulfilling the medical community's requirements for and desired attributes of a rapid molecular TB test (3,36,37). The answer to these questions is especially important when the prevalence of drug resistance in a population is low (Ͻ5%), when RIF resistance alone is used as a surrogate marker for MDR M. tuberculosis, or when the availability of second-line drugs is limited.…”