Risk Factors for Treatment Failure of Drug-Susceptible Pulmonary Tuberculosis in Lithuania over 22 Years

<i>Background and Objectives</i>: This study aimed to evaluate the treatment outcomes of adults with pulmonary drug-susceptible tuberculosis (DS-TB) in Lithuania over 22 years, and to examine associations between treatment outcomes, various risk factors, and temporal trends. <i>Materials and Methods</i>: A retrospective cohort analysis was conducted using data from the National Tuberculosis Information System from 2000 to 2021. A total of 18,697 adult patients with DS-TB were included. Patients were grouped into three time periods: Period I (2000-2007), Period II (2008-2015), and Period III (2016-2021). Treatment outcomes were categorized as successful (treatment completed with recovery) or unsuccessful (patients who encountered treatment failure, died during treatment, or converted to drug-resistant tuberculosis). Associations with individual risk factors, including smoking, alcohol use, comorbidities, and sociodemographic variables, were analyzed. <i>Results</i>: Treatment success rates improved steadily across the study periods: 82.3% in Period I, 84.4% in Period II, and 87.6% in Period III. Mortality rates declined over time but remained substantial: 17.1%, 15.2%, and 12.0% in Periods I, II, and III, respectively. Non-lethal treatment failures decreased slightly (0.6%, 0.4%, and 0.4%). Multivariate analysis identified significant associations between treatment failure and multiple risk factors, including low BMI, male gender, unemployment, homelessness, smoking, alcohol and substance use, and comorbid conditions such as cancer, cardiovascular disease, chronic lung disease, diabetes mellitus, HIV, and renal failure. <i>Conclusions</i>: Treatment outcomes for DS-TB in Lithuania have improved over the past two decades; however, certain modifiable risk factors-such as low BMI, homelessness, substance use, and comorbidities-remain strongly linked to treatment failure. To further improve outcomes, targeted interventions such as nutritional support, housing programs, and integrated addiction services should be prioritized for high-risk groups within national TB control efforts.