Background: Persistent or worsening respiratory symptoms during anti-tubercular therapy may reflect superadded bacterial infection rather than tuberculosis alone. Local pathogen distribution, antimicrobial susceptibility, and preventable host factors are insufficiently characterized in high-burden settings. Aims: To estimate the prevalence and spectrum of secondary bacterial infection in active pulmonary tuberculosis, describe antibiotic susceptibility, as identify modifiable risk factors associated with culture positivity. Materials and Methods: This hospital-based cross-sectional study included 90 adults with bacteriologically confirmed pulmonary tuberculosis who had received anti-tubercular therapy for more than two weeks and had clinical deterioration or inadequate improvement. Sputum was evaluated for pyogenic bacterial culture and antibiotic susceptibility. Associations with culture positivity were assessed by Fisher exact/chi-square testing, odds ratios, and multivariable logistic regression. Results: Secondary bacterial culture was positive in 27 patients (30.0%; 95% CI 21.5-40.1). Gram-negative organisms accounted for 66.7% of isolates. Klebsiella pneumoniae was most frequent (33.3%), followed by Pseudomonas aeruginosa and Staphylococcus aureus (18.5% each). Isolate-level multidrug resistance was present in 22.2%. High susceptibility was observed to meropenem (94.4%), ertapenem (91.7%), piperacillin-tazobactam (88.9%), amikacin (73.9%), and doxycycline (71.4%), while resistance was high to ampicillin (91.7%), ciprofloxacin (73.9%), ceftazidime (66.7%), and levofloxacin (59.3%). Current/former smoking independently predicted culture positivity (adjusted odds ratio 4.07, 95% CI 1.36-12.18; p=0.012). Poor oral hygiene showed a strong borderline adjusted association (adjusted odds ratio 2.76, 95% CI 1.00-7.66; p=0.051). Conclusion: One in three clinically non-improving patients with active pulmonary tuberculosis had culture-positive secondary bacterial infection. Gram-negative pathogens and resistance to commonly used antibiotics were prominent. Culture-guided treatment, smoking cessation, and improved oral hygiene should be integrated into the evaluation of such patients.