Abstract
Background: our objective was to determine the incidence of toxicity among veterans initiating isoniazid therapy for latent tuberculosis infection (LTBI) and determine whether advancing age was a risk factor for toxicity. Methods: we performed a retrospective cohort study among all adults initiating isoniazid treatment for LTBI at a Veterans Medical Center from 1999 to 2005. We collected data on patient demographics, co-morbidities, site of initiation, and treatment outcome. Results: 219 patients initiated isoniazid therapy for LTBI during the period of observation, and the completion of therapy was confirmed in 100 patients (46%). Among 18/219 patients (8%) that discontinued therapy due to a documented suspected toxicity, the median time to onset was 3 months (IQR 1–5 months). In an adjusted Cox regression model, there was no association between discontinuation due to suspected toxicity and advancing age (HR 1.03, 95% CI 0.99, 1.07). In contrast, hepatitis C infection was a significant predictor of cessation due to toxicity in the adjusted analysis (HR 3.03, 95% CI 1.08, 8.52). Conclusions: cessation of isoniazid therapy due to suspected toxicity was infrequently observed among a veteran population and was not associated with advancing age. Alternative LTBI treatment approaches should be further examined in the veteran population.
Highlights
According to World Health Organization estimates, onethird of the world’s population is latently infected with M. tuberculosis, and 10% of immunocompetent individuals will progress from latent to active tuberculosis infection within their lifetimes [1]
219 veterans initiated isoniazid therapy for latent tuberculosis infection (LTBI), with a median age of 53 years. ere were 18 patients (8%) with therapy discontinued due to suspected toxicity, patients (46%) with successful completion of therapy, and patients (46%) with therapy discontinued for unknown reasons
Isoniazid completion rates were higher among residents of the long-term care facility compared with nonresidents (64% versus 44%, PP P PPPP), with similar rates of discontinuation for suspected toxicity between these two groups (9% versus 8%, PP P PPPP)
Summary
According to World Health Organization estimates, onethird of the world’s population is latently infected with M. tuberculosis, and 10% of immunocompetent individuals will progress from latent to active tuberculosis infection within their lifetimes [1]. Subsequent studies of isoniazid toxicity have compared the risk of hepatotoxicity between adults less than and greater than 35 years of age [4,5,6,7,8,9,10], and a meta-analysis of these studies demonstrated a small but statistically signi cant increased risk of hepatotoxicity among adults greater than age 35 [11] Because of these concerns, providers may be more reluctant to initiate isoniazid therapy in older patients with LTBI, in the presence of comorbid illnesses [12]
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