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

Abstract

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 Xpertnegative 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.

Early Empirical Tuberculosis Treatment in HIV-Positive Patients Admitted to Hospital in South Africa: An Observational Cohort Study

“…Two observational studies from sub-Saharan Africa suggested that empirical TB treatment may reduce mortality in smear-negative inpatients; however, these were both conducted prior to the availability of Xpert [ 20 , 21 ]. An Ethiopian study of Xpert-negative hospitalized patients (21% HIV-positive) found substantial overtreatment but no differences in survival [ 22 ]. Data from outpatients have also reported widespread empirical TB treatment despite good availability of Xpert, but similar clinical outcomes, including mortality, between empirically treated and microbiologically confirmed TB patients [ 23 , 24 ].…”

The value of lateral flow urine lipoarabinomannan assay and empirical treatment in Xpert MTB/RIF ultra negative patients with presumptive TB: a prospective cohort study

“…This analysis is a secondary analysis of a cohort study that aimed to determine the role of empiric treatment among hospitalized adults (age ≥ 18 years) with symptoms of pulmonary TB (current cough, night sweats, fever, and weight loss) who could produce a sputum sample and tested negative on the Xpert MTB/RIF assay 24 . For the cohort study, all consecutive hospitalized Xpert MTB/RIF-negative patients were followed to determine if they were started on TB treatment.…”

The Value of Lateral Flow Urine Lipoarabinomannan Assay and Empirical Treatment in the Xpert MTB/RIF Ultra Era: a Prospective Cohort Study

“…This analysis is a secondary analysis of a cohort study that aimed to determine the role of empiric treatment among hospitalized adults (age ≥ 18 years) with symptoms of pulmonary TB (current cough, night sweats, fever, and weight loss) who tested negative on the Xpert MTB/RIF assay [21]. The cohort study enrolled 125 patients treated empirically for active TB and 125 patients in whom the physician decided not to treat for TB.…”