Emergence of bedaquiline resistance among clinical isolates of Multi-Drug Resistant-Mycobacterium tuberculosis from Northern part of India

<bold>Background:</bold> Bedaquiline (BDQ) is a key component in all-oral short regimens for multi-drug resistant tuberculosis (MDR-TB), but BDQ resistance is a growing concern. Despite the reports from numerous countries, frequency of BDQ resistance among MDR-TB patients remains uncertain in India, a country that accounts for 27% of global burden of MDR-TB. <bold>Aim:</bold> Present study aims to determine the frequency and genetic diversity of BDQ resistance among MDR-TB isolates from North India. <bold>Methods:</bold> A total of 243 MDR-Mycobacterium tuberculosis isolates of pulmonary TB patients from North India were collected and subjected to BDQ drug susceptibility testing at World Health Organization recommended critical concentration (MIC≥0.25μg/ml) on 7H11 agar medium. Genomic diversity among BDQ resistant isolates was studied using spoligotyping method. <bold>Results:</bold> The rate of BDQ resistance among MDR-TB isolates was found to be 1.64% (4/243). The frequency of BDQ resistance was higher in patients with medical history of BDQ treatment (7.14%; 1/14) as compared to naïve cases (1.35%, 3/221). Spoligotyping revealed that BDQ resistant isolates belonged to Beijing (SIT1), CAS1_Del (SIT 141), CAS (SIT 2591) and MANU (SIT1318) families. <bold>Conclusions:</bold> Present study provides the baseline data and first evidence for the existence and genotypes of BDQ resistant strains among MDR-TB patients in India. Study highlights that continuous surveillance, strengthening of laboratory capability for BDQ-DST, molecular typing and tracing of resistant strains are urgently needed for better understanding of transmission dynamics and effective management of BDQ resistance in India.