Xpert MTB/RIF-detected Rifampicin Resistance is a Sub-Optimal Surrogate for Multidrug Resistant Tuberculosis in Eastern Democratic Republic of the Congo: Diagnostic and Clinical Implications.

BACKGROUND Rifampicin (RIF) resistance is highly correlated with isoniazid (INH) resistance and used as proxy for multidrugresistant tuberculosis (MDR-TB). Using MTBDRplus as a comparator, we evaluated the predictive value of Xpert® MTB/RIF (Xpert)detected RIF resistance for MDR-TB in eastern Democratic Republic of the Congo (DRC). METHODS We conducted a cross-sectional study involving data from new or retreatment pulmonary adult TB cases evaluated between July 2013 and December 2016. Separate, paired sputa for smear microscopy and MTBDRplus were collected. Xpert testing was performed subject to the availability of Xpert cartridges on sample remnants after microscopy. RESULTS Among 353 patients, 193 (54.7%) were previously treated and 224 (63.5%) were MTBDRplus TB-positive. Of the 224, 43 (19.2%) were RIFmono-resistant, 11 (4.9%) were INHmono-resistant, 53 (23.7%) had MDR-TB, and 117 (52.2%) were RIF- and INH-susceptible. Overall, among the 96 samples detected by MTBDRplus as RIF-resistant, 53 (55.2%) had MDR-TB. Xpert testing was performed in 179 (50.7%) specimens, and amongst these, 163 (91.1%) were TB-positive and 73 (44.8%) RIF-resistant. Only 45/73 (61.6%) Xpertidentified RIF-resistant isolates had concomitant MTBDRplus-detected INH resistance. Xpert had a sensitivity of 100.0% (95% CI; 92.1-100.0) for detecting RIFresistance but a positive predictive value of only 61.6% (95% CI; 49.5-72.8) for MDR-TB. The most frequent mutations associated with RIF and INH resistance were S531L and S315T1, respectively. CONCLUSIONS In this high-risk MDR-TB study population, Xpert had low positive predictive value for the presence of MDR-TB. Comprehensive resistance testing for both INH and RIF should be performed in this setting.