Second time’s the charm? Assessing the sensitivity and yield of inpatient diagnostic algorithms for pulmonary tuberculosis in a low-prevalence setting

Abstract

Abstract Background Among persons with suspected pulmonary tuberculosis, CDC guidelines recommend collecting three respiratory specimens 8-24 hours apart for acid-fast bacilli (AFB) smear and culture, in addition to one nucleic acid amplification test (NAAT). However, data supporting this approach are limited. Our objective was to estimate the performance of one, two, or three AFB smears +/- NAAT to detect pulmonary tuberculosis in a low-prevalence setting. Methods We conducted a retrospective study of hospitalized persons at eight Massachusetts acute care facilities who underwent mycobacterial culture on one or more respiratory specimens between July 2016–December 2022. We evaluated percent positivity and yield on serial AFB smears and on NAAT among people with growth of Mycobacterium tuberculosis on mycobacterial cultures. Results Among 104 participants with culture-confirmed pulmonary tuberculosis, the first AFB smear was positive in 41/104 cases (39%). A second AFB smear was positive in 11/49 cases (22%) in which it was performed. No third AFB smears were positive following two initial negative smears. 36/52 smear-negative cases had NAAT performed, leading to 23 additional diagnoses. Overall sensitivity to detect tuberculosis prior to culture positivity was higher in any strategy involving one or two NAATs (74-79%), even without AFB smears, compared with three smears alone (60%). Conclusions Tuberculosis diagnostic testing with two AFB smears offered the same yield as three AFB smears while potentially reducing laboratory burden and duration of airborne infection isolation. Use of one or two NAATs increased sensitivity to detect culture-positive pulmonary tuberculosis when added to AFB smear-based diagnostic testing alone.