Ferrreira Cynthia de Oliveira, Leturiondo André Luiz, Dos Santos Camila Gurgel, da Silva Jaqueline Bentes, Souza Michelle Fernanda de Andrade, Rego Catherine Bianca Oliveira, de Souza Guilherme Caldas, Pinheiro Thamires Bastos, Melo Gisely Cardoso, Rosa Patricia Sammarco, Mira Marcelo Távora, Avanzi Charlotte, Talhari Carolina
Laboratório de Biologia Molecular, Fundação Hospitalar Alfredo da Matta-FUHAM, Manaus, Amazonas, Brazil.
Genomic Health Surveillance Network: Optimization of Assistance and Research in the State of Amazon (REGESAM), Manaus, Amazonas, Brazil.
Antimicrob Agents Chemother. 2025 Jul 2;69(7):e0155024. doi: 10.1128/aac.01550-24. Epub 2025 May 20.
Multidrug therapy for leprosy is highly effective and the recommended standard of care for leprosy worldwide. However, reports of antimicrobial resistance (AMR) have emerged globally. This study aimed to estimate the frequency of primary and secondary AMR associated with leprosy in patients treated at the Alfredo da Matta Foundation, Manaus, Amazonas, Brazil, as well as to determine the circulating subtypes of in this population. A total of 315 biopsy samples were investigated for variants in leprosy AMR-associated genes (); a subset of 163 samples was also investigated for 5 additional candidate genes: , and . Patients were categorized into new cases, relapses, and suspected treatment failures. For statistical analysis, Pearson's chi-square or Fisher's exact test was employed for categorical variables, while mean and SD were calculated for continuous variables, with a significance level of 5%. Variant analysis detected 10 resistant isolates displaying mutations in the (2, 0.6%) and (8, 2.5%) genes. In addition, variants in (1, 0.6%), (6, 3.7%), (4, 2.4%), and (15, 9.2%) were detected. Nine out of 10 resistant isolates were observed in the relapse group ( = 0,0014). Despite the low variant frequencies observed, variant detection highlights the need for expanded antimicrobial monitoring and surveillance. The impact of mutations in and on therapeutic response remains unclear, underscoring the need for further research. Genotyping revealed subtype-4 predominance (79.6%). Our findings highlight the importance of comprehensive AMR monitoring, particularly in relapse cases.
麻风病的多药疗法非常有效，是全球推荐的麻风病标准治疗方法。然而，全球已出现抗菌药物耐药性（AMR）的报告。本研究旨在估计在巴西亚马孙州马瑙斯的阿尔弗雷多·达马塔基金会接受治疗的麻风病患者中，原发性和继发性AMR的发生频率，并确定该人群中循环的亚型。共对315份活检样本进行了麻风病AMR相关基因（）变异的调查；还对163份样本的子集进行了另外5个候选基因的调查：、和。患者被分为新发病例、复发病例和疑似治疗失败病例。对于统计分析，分类变量采用Pearson卡方检验或Fisher精确检验，连续变量计算均值和标准差，显著性水平为5%。变异分析检测到10株耐药分离株，其在基因（2株，0.6%）和（8株，2.5%）中显示突变。此外，还检测到基因（1株，0.6%）、（6株，3.7%）、（4株，2.4%）和（15株，9.2%）的变异。在复发组中观察到10株耐药分离株中的9株（=0.0014）。尽管观察到的变异频率较低，但变异检测突出了扩大抗菌药物监测和 surveillance 的必要性。和基因中的突变对治疗反应的影响仍不清楚，这凸显了进一步研究的必要性。基因分型显示4型为主（79.6%）。我们的研究结果强调了全面AMR监测的重要性，特别是在复发病例中。
