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印度麻风分枝杆菌氧氟沙星耐药模式的高频率:重新审视二线抗麻风病治疗方案的指征。

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

机构信息

Department of Immunopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh, India.

Department of Dermatology, Venereology & Leprology, PGIMER, Sector-12, Chandigarh, India.

出版信息

J Glob Antimicrob Resist. 2023 Dec;35:262-267. doi: 10.1016/j.jgar.2023.10.006. Epub 2023 Oct 16.

DOI:10.1016/j.jgar.2023.10.006
PMID:37852372
Abstract

OBJECTIVES

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

目的

麻风病的耐药性是一个新出现的问题,导致治疗失败、复发以及社区中潜在耐药麻风分枝杆菌的传播。本研究旨在评估印度一家三级转诊医院麻风病患者的耐药率和耐药模式。

方法

对 136 例麻风病患者(初治患者=67 例,持续皮肤病变患者=35 例,复发患者=34 例)皮肤活检中提取的 DNA 进行药物耐药决定区的突变分析,采用聚合酶链反应(PCR)和 Sanger 测序。野生型菌株(泰国-53)被用作参考菌株。

结果

在总共 23 名患者中发现了耐药突变,占该队列的 16.9%。在这 23 例病例中,有 17 例(12.5%)对氧氟沙星耐药,3 例(2.2%)对二氨苯砜和利福平均耐药。复发和初治病例的氧氟沙星耐药发生率分别为 17.6%和 16.4%,差异极小。二氨苯砜耐药出现在 2 例初治病例和 1 例持续皮肤病变病例中。值得注意的是,初治病例或复发/复发病例中均未发现利福平耐药。随后,未发现其他临床变量与抗菌药物耐药性之间存在统计学相关性。

结论

当前多药治疗方案(特别是二氨苯砜和利福平)和麻风分枝杆菌二线抗麻风药物氧氟沙星耐药的发生令人担忧。这就需要扩大杀菌药物的选择范围,并在麻风病负担较重的国家建立耐药监测。此外,必须采取严格的抗菌药物管理措施。由于这是一项单中心研究,因此只能代表实地情况的有限的横断面观点。

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