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.
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.
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.
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).
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
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% (95% CrI 97% to 99%). As an
add-on test following a negative smear microscopy result (14 studies,
5719 participants), Xpert yielded a pooled sensitivity of 67% (95% CrI
58% to 74%) and pooled specificity of 98% (95% CrI 97% to 99%). In
clinical subgroups, we found the following accuracy estimates: the
pooled sensitivity was 98% (95% CrI 97% to 99%) for smear-positive,
culture-positive TB and 68% (95% CrI 59% to 75%) for smear-negative,
culture-positive TB (15 studies); the pooled sensitivity was 80% (95%
CrI 67% to 88%) in people living with HIV and 89% (95% CrI 81% to 94%)
in people without HIV infection (four studies). For rifampicin
resistance detection (11 studies, 2340 participants), Xpert achieved a
pooled sensitivity of 94% (95% CrI 87% to 97%) and pooled specificity of
98% (95% CrI 97% to 99%). In a separate analysis, Xpert could
distinguish between TB and nontuberculous mycobacteria (NTM) in clinical
samples with high accuracy: among 139 specimens with NTM, Xpert was
positive in only one specimen that grew NTM.
In a hypothetical cohort of 1000 individuals suspected of having
rifampicin resistance (a proxy for MDR-TB), where the prevalence of
rifampicin resistance is 30%, we estimated that on average Xpert would
wrongly identify 14 patients as being rifampicin resistant. In
comparison, where the prevalence of rifampicin resistance is only 2%, we
estimated that the number of individuals wrongly identified as
rifampicin resistant would increase to 20, an increase of 43%.
This review shows that Xpert used as an initial diagnostic test for TB
detection and rifampicin resistance detection in patients suspected of
having TB, MDR-TB, or HIV-associated TB is sensitive and specific. Xpert
may also be valuable as an add-on test following microscopy for patients
who have previously been found to be smear-negative. An Xpert result
that is positive for rifampicin resistance should be carefully
interpreted and take into consideration the risk of MDR-TB in a given
patient and the expected prevalence of MDR-TB in a given setting.
Studies in this review mainly assessed sensitivity and specificity of
the test when used in reference laboratories in research investigations.
Most studies were performed in high TB burden countries. Ongoing use of
Xpert in high TB burden countries will contribute to the evidence base
on the diagnostic accuracy and clinical impact of Xpert in routine
programmatic and peripheral health care settings, including settings
where the test is performed at the point of care.
Steingart, K.R.; Sohn, H.; Schiller, I.; Kloda, L.A.; Boehme, C.C.; Pai, M.; Dendukuri, N. Xpert® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database of Systematic Reviews (2013) (Issue 1) Art. No.: CD009593. [DOI: 10.1002/14651858.CD009593.pub2]
Xpert® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults.