Abstract
BACKGROUND: Drug-resistant tuberculosis (TB) poses a major challenge to global TB control. Understanding local resistance patterns and their determinants is essential for designing effective control strategies. This study investigated the prevalence and risk factors associated with drug-resistant Mycobacterium tuberculosis among patients with pulmonary TB in selected hospitals across Ghana. METHODOLOGY: This prospective, multi-center, cross-sectional study was conducted in selected hospitals in the southern and northern parts of Ghana between August 2019 and August 2020. Sputum samples were collected from tuberculosis-suspected patients and screened for Mycobacterium tuberculosis using GeneXpert MTB/RIF. GeneXpert-positive samples were cultured in Mycobacterial Growth Indicator Tube (MGIT). M. tuberculosis isolates were tested for susceptibility to first-line anti-tuberculosis drugs using MGIT. TB risk factors and demographic data were collected using a structured questionnaire. Data were analyzed using SPSS version 26. RESULTS: Of 167 M. tuberculosis isolates, 17.4% showed resistance to at least one first-line drug. Resistance to rifampicin, isoniazid, streptomycin, and ethambutol was 13.2%, 9.0%, 6.0%, and 5.4%, respectively. Mono-resistance (resistance to only one first-line drug) occurred in 8.4% of isolates, while MDR/RR-TB accounted for 13.2%. Most MDR-TB cases (12.0%) were from new patients. Resistance rates were significantly higher in southern Ghana sites than in northern sites. Southern location was the only independent predictor of resistance (aOR 4.04; 95% CI: 1.57–10.37; p = 0.004), with no associations for sex, age, or alcohol use. CONCLUSION: The relatively high prevalence of rifampicin and isoniazid resistance, along with an MDR/RR-TB rate of 13.2%, underscores a concerning public health challenge. The regional disparity observed suggests the need for enhanced surveillance, targeted interventions, and strengthened treatment monitoring in southern Ghana to curb the spread of resistant TB strains. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-025-12503-z.