FREQUENCY AND DISTRIBUTION OF DRUG RESISTANCE-ASSOCIATED MUTATIONS (RPOB, KATG, INHA, GYRA, RRS AND EIS) IN MYCOBACTERIUM TUBERCULOSIS ISOLATES FROM SOUTHERN PUNJAB

Abstract

Background: The emergence of drug-resistant tuberculosis (DR-TB) has become a major challenge to global tuberculosis control programs. Resistance in Mycobacterium tuberculosis is primarily driven by mutations in specific genes associated with first-line and second-line anti-tuberculous drugs. This study aimed to determine the frequency and distribution of drug resistance-associated mutations in M. tuberculosis isolates from tertiary care hospitals of Southern Punjab, Pakistan.

Methods: A cross-sectional study was conducted on sputum samples collected from suspected tuberculosis patients presenting to four tertiary care hospitals in Southern Punjab, Pakistan, including Nishtar Hospital Multan, Bahawal Victoria Hospital Bahawalpur, Sheikh Zayed Hospital Rahim Yar Khan, and DHQ Hospital Dera Ghazi Khan. Molecular diagnostic techniques were employed to detect mutations associated with resistance to first-line and second-line anti-tuberculosis drugs. The analyzed mutations included rpoB, katG, inhA, gyrA, rrs, and eis genes. Statistical analysis was performed to compare mutation frequencies among study sites. Results: Among the detected resistance-associated mutations, rpoB was the most prevalent mutation, identified in 35.8% of isolates, followed by inhA (25.9%), katG (14.8%), gyrA (9.9%), rrs (8.6%), and eis (4.9%). Hospital-wise analysis showed comparable mutation frequencies across all study sites. The prevalence of rpoB mutation ranged from 34.6% to 37.5%, while inhA mutation ranged from 18.8% to 26.9%. No statistically significant differences were observed in the distribution of any mutation among hospitals (p > 0.05).

Conclusion: The predominance of rpoB and inhA mutations indicates a high burden of rifampicin and isoniazid resistance among M. tuberculosis isolates in Southern Punjab. The uniform distribution of resistance-associated mutations across hospitals suggests widespread circulation of resistant strains in the region. Rapid molecular detection of these mutations can facilitate early diagnosis and guide effective treatment strategies for drug-resistant tuberculosis.