Genotypic analysis of multidrug-resistant tuberculosis isolates from extra pulmonary tuberculosis cases in tertiary care centers in Northern India

Objective/background: Multidrug-resistant tuberculosis (MDR-TB) is a major public health problem. The diagnosis of MDR-TB is of paramount importance in establishing appropriate clinical management and infection control measures. Rapid detection of MDR-TB allows the establishment of an effective treatment regimen, minimizes the risk of further resistance, and limits the spread of drug-resistant strains. The aim of this study is to determine the genotypic characterization of MDR-TB isolates from extra pulmonary tuberculosis (EPTB) cases in tertiary care centers in Northern India.

Methods: This study was a prospective study. In total, 756 extra pulmonary specimens were collected from patients with suspected tuberculosis in two tertiary care hospitals in Northern India. Specimens were processed for Ziehl-Neelsen staining, culture, and first-line drug susceptibility test using BacT/ALERT 3D system and GenoType MTBDRplus assay for genotypic analysis of MDR-TB. MDR-TB strains were further processed by novel multiplex polymerase chain reaction for rapid identification of Beijing and non-Beijing strains associated with MDR-TB.

Results: Of these 164 Mycobacterium tuberculosis complex isolates, 100 (60.9%) strains were fully susceptible and 64 (39.1%) strains were resistant. We noted that the prevalence of MDR-TB among EPTB was 22 (13.4%). The prevalence of MDR-TB was 11.4% in new cases and 19.1% in previously treated cases (p<0.05). Ser531Leu mutation was the predominant mutation noted, and Ser315Thr mutation was more prevalent among the MDR-TB isolates (p<0.05). The proportion of Beijing strains was significantly higher among MDR-TB strains (72.7%, p<0.05).

Conclusion: The prevalence (13.4%) of MDR-TB among EPTB was high, and the most prominent mutations in rpoB, katG, and inhA genes were S531L (67.3%), S315T1 (94.5%), and C15T (20%), respectively. Beijing stains are significantly associated with MDR-TB among EPTB in this region. We found that the transmission of prominent mutations contributes to an unexpected increase in primary resistance, including MDR-TB cases in Northern India.