Impact of Xpert MTB/RIF Testing on Tuberculosis Management and Outcomes in Hospitalized Patients in Uganda

Rationale: The clinical impact of Xpert MTB/RIF for tuberculosis (TB) diagnosis in high HIV-prevalence settings is unknown. Objective: To determine the diagnostic accuracy and impact of Xpert MTB/RIF among high-risk TB suspects. Methods: We prospectively enrolled consecutive, hospitalized, Ugandan TB suspects in two phases: baseline phase in which Xpert MTB/RIF results were not reported to clinicians and an implementation phase in which results were reported. We determined the diagnostic accuracy of Xpert MTB/RIF in reference to culture (solid and liquid) and compared patient outcomes by study phase. Results: 477 patients were included (baseline phase 287, implementation phase 190). Xpert MTB/RIF had high sensitivity (187/237, 79%, 95% CI: 73-84%) and specificity (190/199, 96%, 95% CI: 92-98%) for culture-positive TB overall, but sensitivity was lower (34/81, 42%, 95% CI: 31-54%) among smear-negative TB cases. Xpert MTB/RIF reduced median days-to-TB detection for all TB cases (1 [IQR 0-26] vs. 0 [IQR 0-1], p < 0.001), and for smear-negative TB (35 [IQR 22-55] vs. 22 [IQR 0-33], p = 0.001). However, median days-to-TB treatment was similar for all TB cases (1 [IQR 0-5] vs. 0 [IQR 0-2], p = 0.06) and for smear-negative TB (7 [IQR 3-53] vs. 6 [IQR 1-61], p = 0.78). Two-month mortality was also similar between study phases among 252 TB cases (17% vs. 14%, difference +3%, 95% CI: -21% to +27%, p = 0.80), and among 87 smear-negative TB cases (28% vs. 22%, difference +6%, 95% CI: -34 to +46%, p = 0.77). Conclusions: Xpert MTB/RIF facilitated more accurate and earlier TB diagnosis, leading to a higher proportion of TB suspects with a confirmed TB diagnosis prior to hospital discharge in a high HIV/low MDR TB prevalence setting. However, our study did not detect a decrease in two-month mortality following implementation of Xpert MTB/RIF possibly because of insufficient powering, differences in empiric TB treatment rates, and disease severity between study phases.