Role of empiric treatment in hospitalized patients with Xpert MTB/RIF-negative presumptive pulmonary tuberculosis
Wakjira Kebede1, 2, 4, Gemeda Abebe1, 2, Esayas Kebede Gudina3, Elise De Vos4, Emmanuel Riviere4, Annelies Van Rie4
1 Mycobacteriology Research Center, Jimma University, Ethiopia; 2 School of Medical Laboratory Science, Institute of Health, Jimma University, Ethiopia; 3Department of Internal Medicine, Jimma University Medical Center, Jimma University, Ethiopia; 4Department of Epidemiology and Social Medicine, Faculty of Medicine and Health sciences, University of Antwerp, Antwerp, Belgium
Introduction: The ability of clinical algorithms to accurately identify tuberculosis disease and the impact of empiric treatment on survival in people with a negative Xpert MTB/RIF (Xpert) result remains poorly documented. This study aimed at determining the ability of clinical algorithms to detect tuberculosis disease and ascertaining the influence of empiric therapy on survival in people with a negative Xpert MTB/RIF (Xpert) result. Sputum samples from 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 examined for Mycobacterium tuberculosis by liquid and solid culture. All study participants were followed up for six months to document survival. The positive predictive value of the clinical algorithm for diagnosis of bacteriological confirmed tuberculosis was evaluated. Logistic regression was used to identify factors associated with bacteriological confirmation and empiric tuberculosis treatment initiation. 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 tuberculosis (10.3% vs 4.3%, p = 0.12). Even though cardinal symptoms of tuberculosis were associated with both bacteriological confirmation and a decision to start empiric treatment, the predictive value of the clinical algorithm was poor (positive predictive value = 24.8%) and empiric treatment did not affect six-month risk of death (5.6% vs 4.8%, p = 0.78). Clinical algorithm led to recognition of the majority of confirmed tuberculosis cases among Xpert-negative inpatients. Per observations, there was no effect of empiric treatment on survival but it resulted in substantial overtreatment. They emphasize employing more sensitive Xpert Ultra assay to eliminate the necessity for empiric tuberculosis treatment.