High frequency of ofloxacin resistance patterns of Mycobacterium leprae from India: An indication to revisit second line anti-leprosy treatment regimen

• Published in: Journal of global antimicrobial resistance. 2023-12, Vol.35, p.262-267
• Main Authors: Chhabra, Seema, Narang, Tarun, Sahu, Smrity, Sharma, Keshav, Shilpa, Shilpa, Sharma, Ayush, Jain, Sejal, Singh, Itu, Yadav, Rakesh, Kaur, Manjot, Sharma, Rahul, Nadeem, Mohd, Pandey, Pragati, Minz, Ranjana W, Dogra, Sunil
• Format: Article
• Language: English
• Subjects: Cross-Sectional Studies; Dapsone - pharmacology; Dapsone - therapeutic use; Drug resistance; Drug Resistance, Bacterial - genetics; Drug Therapy, Combination; Humans; India - epidemiology; Leprostatic Agents - pharmacology; Leprostatic Agents - therapeutic use; Leprosy; Leprosy - drug therapy; Leprosy - epidemiology; Mycobacterium leprae - genetics; North India; Ofloxacin; Ofloxacin - pharmacology; Persistent skin lesions; Relapse; Rifampin - pharmacology; Rifampin - therapeutic use
• ISSN: 2213-7165; 2213-7173
• DOI: 10.1016/j.jgar.2023.10.006

Drug resistance in leprosy is an emerging concern, leading to treatment failures, recurrences, and potential spread of resistant Mycobacterium leprae in the community. In this study, we aimed to assess drug resistance prevalence and patterns amongst leprosy patients at a tertiary care referral hospital in India. Mutations in drug resistance determining regions for dapsone, rifampicin, and ofloxacin of the M. leprae genome in DNA extracted from skin biopsies of 136 leprosy patients (treatment-naive = 67, with persistent skin lesions = 35, with recurrence = 34) were analysed by polymerase chain reaction followed by Sanger sequencing. Wild-type strain (Thai-53) was used as a reference strain. Resistance mutations were identified in a total of 23 patients, constituting 16.9% of the cohort. Within this subset of 23 cases, resistance to ofloxacin was observed in 17 individuals (12.5%), while resistance to both dapsone and rifampicin was detected in three patients each (2.2% for both). The occurrence of ofloxacin resistance showed minimal disparity between recurrent and treatment-naive cases, at 17.6% and 16.4%, respectively. Dapsone resistance emerged in two treatment-naive cases and one case with persistent skin lesions. Notably, none of the treatment-naive cases or those with recurrence/relapse exhibited rifampicin resistance. Subsequently, no statistically significant correlation was identified between other clinical variables and the presence of antimicrobial resistance. The occurrence of resistance to the current multidrug therapy regimen (specifically dapsone and rifampicin) and to ofloxacin, a secondary antileprosy medication in M. leprae, represents a concerning scenario. This calls for an expansion towards bactericidal drug options and the establishment of robust surveillance for drug resistance in countries burdened with high leprosy rates. Moreover, the introduction of stringent antimicrobial stewardship initiatives is imperative. As a single centre study, it represents a limited, cross-sectional view of the real situation in the field.