Accuracy of Xpert MTB/RIF Ultra for the Diagnosis of Pleural TB in a Multicenter Cohort Study.

The Xpert MTB/RIF (Xpert) assay has greatly improved the diagnosis of TB and identification of resistance to rifampicin (RIF). However, sensitivity of Xpert remains poor for pleural fluid detection. This study evaluated the performance of the novel next-generation Xpert MTB/RIF Ultra (Xpert Ultra) in comparison with Xpert for pleural TB diagnosis. Patients with suspected pleural TB were enrolled consecutively in four hospitals, and pleural fluids were subjected to smear, culture, and Xpert. Defrosted pleural fluid (-80°C) was examined using Xpert Ultra. Drug susceptibility testing (DST) was conducted for all of the recovered isolates. In total, 317 individuals with suspected pleural TB were recruited; 208 of them were diagnosed with pleural TB according to the composite reference standard, which was composed of clinical, laboratory, histopathologic, and radiologic examination features and ≥ 12 months of follow-up data. The direct head-to-head comparison for Mycobacterium tuberculosis detection showed that Xpert Ultra (44.23%, 92 of 208) produced a higher sensitivity than culture (26.44%, 55 of 208, P < .001), Xpert (19.23%, 40 of 208, P < .001), and smear (1.44%, three of 208, P < .001). When Xpert Ultra outcomes were integrated, the percentage of definite pleural TB cases increased from 56.25% (117 of 208) to 64.90% (135 of 208). The specificities of smear, culture, Xpert, and Xpert Ultra were 100% (84 of 84), 100% (84 of 84), 98.67% (83 of 84), and 98.67% (83 of 84), respectively. Xpert Ultra was 100% concordant with phenotype DST for the detection of RIF resistance. Xpert Ultra has great potential in diagnosis of pleural TB and its RIF resistance, which could speed up the initiation of appropriate treatment.

Wang G ，Wang S ，Yang X ，Sun Q ，Jiang G ，Huang M ，Huo F ，Ma Y ，Chen X ，Huang H ... -  《-》

Diagnostic value of Xpert MTB/RIF Ultra for osteoarticular tuberculosis.

The diagnosis of osteoarticular tuberculosis (TB) remains challenging and results in under- or over-diagnosis. The aim of the present study was to evaluate performance of the novel next-generation Xpert MTB/RIF Ultra (Xpert Ultra) in comparison to culture and Xpert MTB/RIF (Xpert) for osteoarticular TB diagnosis in high burden settings. Osteoarticular TB suspected cases were enrolled consecutively during June 2017 to June 2018 at Beijing Chest Hospital and their pus specimens were subjected to smear, culture, Xpert and Xpert Ultra. Drug susceptibility testing (DST) was conducted for all of the recovered isolates. The performances of Xpert Ultra and Xpert were evaluated using composite reference standard (CRS) as gold standard, which included clinical, laboratory, histopathological, radiological and ≥6 months' follow-up data. In total, 186 patients were recruited, and 132 of them were diagnosed with osteoarticular TB according to CRS. The direct head-to-head performance comparison for M. tuberculosis detection showed that Xpert Ultra (90.91%, 120/132) produced a higher sensitivity than Xpert (78.79%, 104/132, P = 0.006) and culture (39.39%, 52/132, P < 0.001). When Xpert Ultra outcomes were integrated, the percentage of confirmed osteoarticular TB case increased from 84.09% (111/132) to 93.94% (124/132). The specificities of Xpert and Xpert Ultra were 100% (34/34) and 97.06% (33/34), respectively. Both Xpert Ultra and Xpert accurately identified all of the 9 rifampicin (RIF)-resistant and 38 RIF-sensitive cases defined by phenotypic DST. Therefore, Xpert Ultra was 100% concordant with phenotypic DST for the detection of RIF resistance. Xpert Ultra detected significantly more osteoarticular TB cases than Xpert or culture, making it a useful tool for rapid diagnosis of osteoarticular TB.

Sun Q ，Wang S ，Dong W ，Jiang G ，Huo F ，Ma Y ，Huang H ，Wang G ... -  《-》

Xpert MTB/RIF Ultra and Xpert MTB/RIF assays for extrapulmonary tuberculosis and rifampicin resistance in adults.

Xpert MTB/RIF Ultra (Xpert Ultra) and Xpert MTB/RIF are World Health Organization (WHO)-recommended rapid nucleic acid amplification tests (NAATs) widely used for simultaneous detection of Mycobacterium tuberculosis complex and rifampicin resistance in sputum. To extend our previous review on extrapulmonary tuberculosis (Kohli 2018), we performed this update to inform updated WHO policy (WHO Consolidated Guidelines (Module 3) 2020). To estimate diagnostic accuracy of Xpert Ultra and Xpert MTB/RIF for extrapulmonary tuberculosis and rifampicin resistance in adults with presumptive extrapulmonary tuberculosis. Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, Web of Science, Latin American Caribbean Health Sciences Literature, Scopus, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, the International Standard Randomized Controlled Trial Number Registry, and ProQuest, 2 August 2019 and 28 January 2020 (Xpert Ultra studies), without language restriction. Cross-sectional and cohort studies using non-respiratory specimens. Forms of extrapulmonary tuberculosis: tuberculous meningitis and pleural, lymph node, bone or joint, genitourinary, peritoneal, pericardial, disseminated tuberculosis. Reference standards were culture and a study-defined composite reference standard (tuberculosis detection); phenotypic drug susceptibility testing and line probe assays (rifampicin resistance detection). Two review authors independently extracted data and assessed risk of bias and applicability using QUADAS-2. For tuberculosis detection, we performed separate analyses by specimen type and reference standard using the bivariate model to estimate pooled sensitivity and specificity with 95% credible intervals (CrIs). We applied a latent class meta-analysis model to three forms of extrapulmonary tuberculosis. We assessed certainty of evidence using GRADE. 69 studies: 67 evaluated Xpert MTB/RIF and 11 evaluated Xpert Ultra, of which nine evaluated both tests. Most studies were conducted in China, India, South Africa, and Uganda. Overall, risk of bias was low for patient selection, index test, and flow and timing domains, and low (49%) or unclear (43%) for the reference standard domain. Applicability for the patient selection domain was unclear for most studies because we were unsure of the clinical settings. Cerebrospinal fluid Xpert Ultra (6 studies) Xpert Ultra pooled sensitivity and specificity (95% CrI) against culture were 89.4% (79.1 to 95.6) (89 participants; low-certainty evidence) and 91.2% (83.2 to 95.7) (386 participants; moderate-certainty evidence). Of 1000 people where 100 have tuberculous meningitis, 168 would be Xpert Ultra-positive: of these, 79 (47%) would not have tuberculosis (false-positives) and 832 would be Xpert Ultra-negative: of these, 11 (1%) would have tuberculosis (false-negatives). Xpert MTB/RIF (30 studies) Xpert MTB/RIF pooled sensitivity and specificity against culture were 71.1% (62.8 to 79.1) (571 participants; moderate-certainty evidence) and 96.9% (95.4 to 98.0) (2824 participants; high-certainty evidence). Of 1000 people where 100 have tuberculous meningitis, 99 would be Xpert MTB/RIF-positive: of these, 28 (28%) would not have tuberculosis; and 901 would be Xpert MTB/RIF-negative: of these, 29 (3%) would have tuberculosis. Pleural fluid Xpert Ultra (4 studies) Xpert Ultra pooled sensitivity and specificity against culture were 75.0% (58.0 to 86.4) (158 participants; very low-certainty evidence) and 87.0% (63.1 to 97.9) (240 participants; very low-certainty evidence). Of 1000 people where 100 have pleural tuberculosis, 192 would be Xpert Ultra-positive: of these, 117 (61%) would not have tuberculosis; and 808 would be Xpert Ultra-negative: of these, 25 (3%) would have tuberculosis. Xpert MTB/RIF (25 studies) Xpert MTB/RIF pooled sensitivity and specificity against culture were 49.5% (39.8 to 59.9) (644 participants; low-certainty evidence) and 98.9% (97.6 to 99.7) (2421 participants; high-certainty evidence). Of 1000 people where 100 have pleural tuberculosis, 60 would be Xpert MTB/RIF-positive: of these, 10 (17%) would not have tuberculosis; and 940 would be Xpert MTB/RIF-negative: of these, 50 (5%) would have tuberculosis. Lymph node aspirate Xpert Ultra (1 study) Xpert Ultra sensitivity and specificity (95% confidence interval) against composite reference standard were 70% (51 to 85) (30 participants; very low-certainty evidence) and 100% (92 to 100) (43 participants; low-certainty evidence). Of 1000 people where 100 have lymph node tuberculosis, 70 would be Xpert Ultra-positive and 0 (0%) would not have tuberculosis; 930 would be Xpert Ultra-negative and 30 (3%) would have tuberculosis. Xpert MTB/RIF (4 studies) Xpert MTB/RIF pooled sensitivity and specificity against composite reference standard were 81.6% (61.9 to 93.3) (377 participants; low-certainty evidence) and 96.4% (91.3 to 98.6) (302 participants; low-certainty evidence). Of 1000 people where 100 have lymph node tuberculosis, 118 would be Xpert MTB/RIF-positive and 37 (31%) would not have tuberculosis; 882 would be Xpert MTB/RIF-negative and 19 (2%) would have tuberculosis. In lymph node aspirate, Xpert MTB/RIF pooled specificity against culture was 86.2% (78.0 to 92.3), lower than that against a composite reference standard. Using the latent class model, Xpert MTB/RIF pooled specificity was 99.5% (99.1 to 99.7), similar to that observed with a composite reference standard. Rifampicin resistance Xpert Ultra (4 studies) Xpert Ultra pooled sensitivity and specificity were 100.0% (95.1 to 100.0), (24 participants; low-certainty evidence) and 100.0% (99.0 to 100.0) (105 participants; moderate-certainty evidence). Of 1000 people where 100 have rifampicin resistance, 100 would be Xpert Ultra-positive (resistant): of these, zero (0%) would not have rifampicin resistance; and 900 would be Xpert Ultra-negative (susceptible): of these, zero (0%) would have rifampicin resistance. Xpert MTB/RIF (19 studies) Xpert MTB/RIF pooled sensitivity and specificity were 96.5% (91.9 to 98.8) (148 participants; high-certainty evidence) and 99.1% (98.0 to 99.7) (822 participants; high-certainty evidence). Of 1000 people where 100 have rifampicin resistance, 105 would be Xpert MTB/RIF-positive (resistant): of these, 8 (8%) would not have rifampicin resistance; and 895 would be Xpert MTB/RIF-negative (susceptible): of these, 3 (0.3%) would have rifampicin resistance. Xpert Ultra and Xpert MTB/RIF may be helpful in diagnosing extrapulmonary tuberculosis. Sensitivity varies across different extrapulmonary specimens: while for most specimens specificity is high, the tests rarely yield a positive result for people without tuberculosis. For tuberculous meningitis, Xpert Ultra had higher sensitivity and lower specificity than Xpert MTB/RIF against culture. Xpert Ultra and Xpert MTB/RIF had similar sensitivity and specificity for rifampicin resistance. Future research should acknowledge the concern associated with culture as a reference standard in paucibacillary specimens and consider ways to address this limitation.

Kohli M ，Schiller I ，Dendukuri N ，Yao M ，Dheda K ，Denkinger CM ，Schumacher SG ，Steingart KR ... -  《Cochrane Database of Systematic Reviews》

Comparison of Xpert MTB/RIF with other nucleic acid technologies for diagnosing pulmonary tuberculosis in a high HIV prevalence setting: a prospective study.

Scott LE ，McCarthy K ，Gous N ，Nduna M ，Van Rie A ，Sanne I ，Venter WF ，Duse A ，Stevens W ... -  《-》

Xpert(®) MTB/RIF assay for extrapulmonary tuberculosis and rifampicin resistance.

Kohli M ，Schiller I ，Dendukuri N ，Dheda K ，Denkinger CM ，Schumacher SG ，Steingart KR ... -  《Cochrane Database of Systematic Reviews》