Clinical Characteristics of Active Tuberculosis Diagnosed after Starting Treatment for Latent Tuberculosis Infection

BACKGROUND: Efforts to expand treatment of latent tuberculosis infection (LTBI) raise concerns for missed subclinical active tuberculosis (TB) and acquired drug-resistance. METHODS: We conducted a retrospective cohort review of patients who began LTBI therapy between January 1, 2006 and December 31, 2017 at the Denver Metro TB Clinic, Colorado, USA. Electronic databases and chart review were used for data collection. Subsequent active TB diagnoses in this cohort were determined using the state of Colorado TB database through June 30, 2018. RESULTS: 8472 patients started LTBI treatment during the study period with 46% prescribed nine months of isoniazid and 43% four months of rifampin. 24 (0.28%) developed active TB, 10 during and 14 after LTBI therapy. Culture confirmation was obtained for 13 (54%) and none had acquired drug-resistance. Patients diagnosed during (n=10) versus after treatment (n=14) were less likely to be culture-confirmed (30% versus 71%) and less likely to have pulmonary disease (20% vs 57%). CONCLUSIONS: Subclinical TB missed by symptom screening and chest radiography was rare in our mostly HIV-negative cohort. Culture negative, extrapulmonary disease was more common with TB diagnosed during than after LTBI treatment. We found no evidence for acquired drug resistance in LTBI patients subsequently diagnosed with active TB.