Factors associated with extended treatment duration in patients with drug-susceptible pulmonary tuberculosis: a prospective multicentre cohort study in South Korea

The standard treatment for drug-susceptible tuberculosis (TB) is a 6-month short-course regimen; however, extended courses are often used in clinical practice. We aimed to identify factors associated with extended treatment in patients with drug-susceptible TB. We conducted a prospective cohort study across 18 institutions in the Republic of Korea between July 2019 and June 2023 and enrolled patients with drug-susceptible TB who received the standard short-course regimen (isoniazid, rifampin, pyrazinamide, and ethambutol) and achieved treatment success at end of therapy. Patients were categorised by treatment duration: less than 200 days (standard treatment group) and more than 200 days (extended treatment group). Of 854 patients, 334 (39.1%) received extended treatment, and 520 (60.9%) received standard treatment. Baseline characteristics differed between groups (extended vs. standard): diabetes mellitus (31.4% vs. 22.5%; P = 0.01), a history of TB treatment (22.2% vs. 10.4%; P < 0.01), multilobar involvement (47.2% vs. 34.3%; P < 0.01), cavitary lesions on chest radiography (32.1% vs. 12.5%; P < 0.01), acid-fast bacillus (AFB) smear positivity (38.9% vs. 14.2%; P < 0.01), gastrointestinal adverse reactions (48.8% vs. 41.9%; P < 0.05), and treatment interruption > 7 days (11.1% vs. 3.1%; P < 0.01). In weighted logistic regression, previous TB (odds ratio [OR] 2.66, 95% confidence interval [CI] 1.67–4.25; P < 0.01), cavity (OR 2.56, 95% CI 1.63–4.02; P < 0.01), and AFB smear positivity (OR 4.06, 95% CI 2.73–6.04; P < 0.01) were significant baseline predictors of extended treatment. In the time-updated Cox analysis, older age (adjusted hazard ratio [aHR] 0.84, 95% CI 0.75–0.95; P < 0.01) and lower body mass index (aHR 0.95, 0.90–0.99; P = 0.02) were associated with a decreased likelihood of extended treatment. In contrast, cardiovascular disease (aHR 1.20, 1.06–1.36; P = 0.01), chronic lung disease (aHR 1.10, 1.01–1.19; P = 0.03), chronic kidney disease (aHR 1.15, 1.01–1.31; P = 0.03), malignancy (aHR 1.16, 1.03–1.30; P = 0.01), previous TB (aHR 1.09, 1.02–1.15; P = 0.01), and cavity (aHR 1.06, 1.01–1.12; P = 0.03) were positively associated with extended treatment. Among time-dependent factors, leucopenia (aHR 1.08, 1.02–1.16; P = 0.02) and 2-month culture positivity (aHR 1.09, 1.01–1.18; P = 0.03) were associated with an increased likelihood of extended treatment, whereas neuropathy (aHR 0.89, 0.80–0.98; P = 0.02) and nephrotoxicity (aHR 0.89, 0.80–0.98; P = 0.02) were associated with a decreased likelihood. This study identified patient and treatment factors associated with extended therapy for drug-susceptible TB in the Republic of Korea, underscoring the need for targeted interventions and strengthened monitoring to optimise treatment outcomes. This study was registered with the Clinical Research Information Service (CRIS), Republic of Korea (https://cris.nih.go.kr, registration number KCT0002594) on 1 November 2017.