Role of empiric treatment in hospitalized patients with Xpert MTB/RIF-negative presumptive pulmonary tuberculosis: A prospective cohort study

Objectives: The ability of clinical algorithms to identify tuberculosis disease and the impact of empiric treatment on survival in people with a negative Xpert MTB/RIF (Xpert) result remains poorly documented.

Methods: Hospitalized Xpert-negative patients (125 initiated on empiric tuberculosis treatment based on a clinical algorithm and 125 in whom tuberculosis treatment was not started) were enrolled. Sputum samples were evaluated for Mycobacterium tuberculosis by culture. All study participants were followed up for 6 months.

Results: Xpert-negative inpatients in whom empiric tuberculosis treatment was initiated were more likely to have microbiological confirmed tuberculosis compared to those in whom empiric tuberculosis treatment was not started (24.8% vs 6.4%, p=0.0001). Six-month risk of death was 5.2%, but the risk was twice as high in people with bacteriological confirmation of TB (10.3% vs 4.3%, p=0.12). Cardinal symptoms of TB were associated with bacteriological confirmation and a decision to start empiric treatment. The positive predictive value of the clinical algorithm was 24.8% and empiric treatment did not affect 6-month risk of death (5.6% vs 4.8%, p=0.78).

Conclusions: Clinical algorithm identifies the majority of confirmed tuberculosis cases among Xpert-negative inpatients. Empiric treatment did not impact survival and resulted in substantial overtreatment. The more sensitive Xpert Ultra assay should be used to eliminate the need for empiric tuberculosis treatment.