Comparative Analysis of Culture and Sputum Smear Conversion Timelines and Their Associated Factors in Smokers Versus Non-smokers With Drug-Resistant Tuberculosis

Background Drug-resistant tuberculosis (DR-TB) is a global health challenge, with smoking potentially affecting treatment outcomes. Smoking compromises immune function and may interfere with the pharmacokinetics of anti-TB drugs. Delayed sputum smear and culture conversion are key indicators of prolonged treatment and infectiousness. This study explores the impact of smoking on these conversion timelines in DR-TB patients. Objective To identify and assess the overall treatment outcomes and the factors associated with delayed culture and sputum smear conversion in smokers compared to non-smokers among patients with drug-resistant tuberculosis. Methods This prospective cohort study was conducted at the Programmatic Management of Drug-Resistant TB (PMDT) unit at Mardan Medical Complex in Khyber-Pakhtunkhwa, Pakistan, from June 2020 to December 2024. All patients diagnosed with drug-resistant tuberculosis (DR-TB) were categorized into two groups based on their smoking status: smokers and non-smokers. Patient demographic and clinical information was collected through structured interviews and standardized questionnaires. The time to sputum smear and culture conversion (SCC) was longitudinally measured from the start of treatment until the patient achieved two consecutive negative smears and three consecutive negative cultures, respectively. Cox proportional hazards analysis was employed to evaluate the relationship between smoking status and time to SCC, adjusting for potential confounding factors. Kaplan-Meier survival curves were used to compare the time to SCC between the two groups, with statistical significance set at p < 0.05. Analyses were performed using SPSS software (version 29.0). Results Out of 281 DR-TB patients, 138 were smokers (49.12%) and 143 were non-smokers (50.88%). Non-smokers achieved faster sputum and culture conversion, with survival proportions dropping to 0.000 by 90 and 70 days, respectively. In contrast, smokers showed slower declines, with sputum conversion at 0.137 and culture conversion at 0.035 by 120 days. The mean sputum conversion time was 59 days for non-smokers and 104 days for smokers, while culture conversion took 43 days for non-smokers and 98 days for smokers. Multivariate analysis identified significant determinants for both groups: older age (≥36 years), lower BMI (<16 kg/m²), and higher sputum smear grades. Non-smokers were adversely affected by gastrointestinal upset and nephrotoxicity, while smokers were more negatively impacted by higher cigarette consumption, diabetes, and lung lesions. Long-term treatment regimens and resistance to antibiotics like levofloxacin and moxifloxacin reduced conversion rates in both groups. Conclusion Smoking not only impairs immune function but also influences the pharmacokinetics of anti-TB drugs, potentially leading to more prolonged and complicated treatment courses.