Second Time's the Charm? Assessing the Sensitivity and Yield of Inpatient Diagnostic Algorithms for Pulmonary Tuberculosis in a Low-Prevalence Setting.

Background: For persons with suspected pulmonary tuberculosis, the guidelines of the Centers for Disease Control and Prevention recommend collecting 3 respiratory specimens 8 to 24 hours apart for acid-fast bacilli (AFB) smear and culture, in addition to 1 nucleic acid amplification test (NAAT). However, data supporting this approach are limited. Our objective was to estimate the performance of 1, 2, or 3 AFB smears with or without NAATs to detect pulmonary tuberculosis in a low-prevalence setting. Methods: We conducted a retrospective study of hospitalized persons at 8 Massachusetts acute care facilities who underwent mycobacterial culture on 1 or more respiratory specimens between July 2016 and December 2022. We evaluated percentage positivity and yield on serial AFB smears and NAATs among people with growth of Results: Among 104 participants with culture-confirmed pulmonary tuberculosis, the first AFB smear was positive in 41 cases (39%). A second AFB smear was positive in 11 (22%) of the 49 cases in which it was performed. No third AFB smears were positive following 2 initial negative smears. Of 52 smear-negative cases, 36 had a NAAT performed, leading to 23 additional diagnoses. Overall sensitivity to detect tuberculosis prior to culture positivity was higher in any strategy involving 1 or 2 NAATs (74%-79%), even without AFB smears, as compared with 3 smears alone (60%). Conclusions: Tuberculosis diagnostic testing with 2 AFB smears offered the same yield as 3 AFB smears while potentially reducing laboratory burden and duration of airborne infection isolation. Use of 1 or 2 NAATs increased sensitivity to detect culture-positive pulmonary tuberculosis when added to AFB smear-based diagnostic testing alone.