Evaluation Of Xpert MTB/RIF On Osteoarticular Tissue For The Diagnosis Of Tuberculosis And Rifampin Resistance

Objective:The Xpert MTB/RIF assay(Xpert; Cepheid, Sunnyvale, CA, USA) is a rapid, endorsed by the World Health Organization for the detection of pulmonary TB, automated PCR test optimised for respiratory specimens that can detect both Mycobacterium tuberculosis(MTB) and rifampicin resistance[1]. Some studies on Xpert have described good performance when testing tissue from various EPTB sites(e.g. lymph node). suggesting that it could be an alternative to culture in tissue specimens,And most of these studies have used only a culture reference standard[2].But the utility of the Xpert MTB/RIF test for the diagnosis of BJTB remains unclear, The aim of the present study was to determine the diagnostic accuracy of Xpert MTB/RIF in a large series of pus amples from patients with suspected BJTB. Evaluate the sensitivity and specificity of Xpert MTB/RIF for the diagnosis of BJTB. Methods:We enrolled consecutive patients that were evaluated for BJTB in the Department of Orthopedics,the 309 th Hospital of PLA, And Beijing Chest Hospital, Capital Medical University. Information on demographics, comorbidities. presenting symptoms and results of diagnostic evaluation were collected prospectively. All recruited patients underwent surgery or punture for evaluation of osteoarticular tissue and the sample was divided into following tests:One specimen was processed with routine diagnostics including fluorescence smear microscopy, liquid cultures(Mycobacterium Growth Indicator Tube; Becton Dickinson. Sparks. MD. USA) and solid cultures(Lo ¨wenstein–Jensen medium), and all positive cultures were tested by phenotypic drug susceptibility testing(DST). and the other in the research laboratory. where the technologist performed the Xpert assay, thus blinding the technologists to the results of other tests. The third sample was evaluated with histopathology. culture is considered the usual diagnostic gold standard. albeit imperfect, as culture are often negative due to the paucibacillary nature of BJTB. Therefore, we have also compared it to a composite reference standard(CRS) to evaluate the true diagnostic potential of the Xpert test for BJTB. The CRS for this study was composed of smear microscopy. culture(both liquid and solid), clinical findings, histology/cytology, site-specific computerized tomography scan/magnetic resonance imaging, and follow-up(FU) after 3 months from the date of enrollment. Based on the CRS. patients were categorized into 4 groups:confirmed TB cases probable TB cases, possible TB cases, and not TB. Xpert sensitivity and specificity results were assessed in comparison to a composite reference standard. Results:Of the 320 recruited patients, there were 8 exclusions, We finally enrolled 312 patients between August 2015 and March 2014. The median age of the patients was 42 years and The male-to-female ratio was 1.3︰1. Of these, 253/312 included patients were diagnosed with BJTB, of whom122 were classified as having definite TBM was culture confirmed. 104 as having probable TBM, 27 as having possible TBM, and 59 as not having TBM. Upon comparison with a composite reference standard, Sensitivities of Xpert, MGIT culture and smear among patients diagnosed with TBM were 78.7%(199 out of 253; 95% CI,73.1-83.5%), 48.2%(122 out of 253; 95% CI41.9-54.6%)and 24.5%(62 out of 253; 95% CI 19.3-30.3%),respectively, And both specificity is 100%(59 out of 59). Xpert detected 121 out of 122 patients with confirmed TB as defined by culture, resulting in a sensitivity of 99.2%(95% CI 95.5%–100%). 253 BJBT sample defineded by CRS, Xpert with a 99.2%(121/122) sensitivity for culture positive cases, a 59.5%(78/131) sensitivity for culture-negative cases. There were 29 sample was RIF resistance by phenotypic DST but 3 of these sample was Xpert sensitive; and 93 sample was RIF sensitive by phenotypic DST but 1 of there samples were Xpert negative and 4 sample was RIF resistance by Xpert;. The sensitivity and specificity of the Xpert test compared to phenotypic DST were found to be 89.7%(26/29) for correctly determining RIF resistance and 94.6%(88/93) for correctly determining RIF susceptibility. Conclution :In conclusion, Culture, however, is limited in its ability to detect BJTB and the comparison to only culture confirmed cases is likely to overestimate the sensitivity of Xpert. we found that the sensitivity of Xpert MTB/RIF was significantly better than that of smear microscopy and the cultur, and is linked to a positive culture. Although the role of culture remains gold standard in the microbiological diagnosis of BJTB, the sensitivity of Xpert in rapidly diagnosing the disease makes it a much better choice compared to culture. The Xpert MTB/RIF represents a significant advance in the early diagnosis of BJTB.