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麻风分枝杆菌耐药性:2009-2015 年世卫组织监测网络开展的首次前瞻性开放性调查结果。

Antimicrobial resistance in leprosy: results of the first prospective open survey conducted by a WHO surveillance network for the period 2009-15.

机构信息

Université Paris Diderot, UMR 1137 IAME Inserm, APHP-Lariboisière, APHP-Pitie-Salpêtrière, Centre de Référence des Mycobactéries et de la résistance des mycobactéries aux antituberculeux, Paris, France.

American Leprosy Missions, Greenville, SC, USA.

出版信息

Clin Microbiol Infect. 2018 Dec;24(12):1305-1310. doi: 10.1016/j.cmi.2018.02.022. Epub 2018 Mar 1.

Abstract

OBJECTIVES

Antimicrobial resistance (AMR) is a priority for surveillance in bacterial infections. For leprosy, AMR has not been assessed because Mycobacterium leprae does not grow in vitro. We aim to obtain AMR data using molecular detection of resistance genes and to conduct a prospective open survey of resistance to antileprosy drugs in countries where leprosy is endemic through a WHO surveillance network.

METHODS

From 2009 to 2015, multi-bacillary leprosy cases at sentinel sites of 19 countries were studied for resistance to rifampicin, dapsone and ofloxacin by PCR sequencing of the drug-resistance-determining regions of the genes rpoB, folP1 and gyrA.

RESULTS

Among 1932 (1143 relapse and 789 new) cases studied, 154 (8.0%) M. leprae strains were found with mutations conferring resistance showing 182 resistance traits (74 for rifampicin, 87 for dapsone and 21 for ofloxacin). Twenty cases showed rifampicin and dapsone resistance, four showed ofloxacin and dapsone resistance, but no cases were resistant to rifampicin and ofloxacin. Rifampicin resistance was observed among relapse (58/1143, 5.1%) and new (16/789, 2.0%) cases in 12 countries. India, Brazil and Colombia reported more than five rifampicin-resistant cases.

CONCLUSIONS

This is the first study reporting global data on AMR in leprosy. Rifampicin resistance emerged, stressing the need for expansion of surveillance. This is also a call for vigilance on the global use of antimicrobial agents, because ofloxacin resistance probably developed in relation to the general intake of antibiotics for other infections as it is not part of the multidrug combination used to treat leprosy.

摘要

目的

抗微生物药物耐药性(AMR)是细菌感染监测的重点。由于麻风分枝杆菌无法在体外生长,因此尚未对麻风分枝杆菌的 AMR 进行评估。我们的目标是通过耐药基因的分子检测获得 AMR 数据,并通过世卫组织监测网络在流行麻风病的国家对利福平、氨苯砜和氧氟沙星抗麻风病药物耐药性进行前瞻性开放调查。

方法

2009 年至 2015 年,对 19 个国家监测点的多菌型麻风病例进行了利福平、氨苯砜和氧氟沙星耐药性的研究,方法是通过耐药基因 rpoB、folP1 和 gyrA 的耐药决定区的 PCR 测序检测耐药性。

结果

在所研究的 1932 例(1143 例复发和 789 例新发病例)中,发现 154 株(8.0%)麻风分枝杆菌菌株具有耐药性突变,表现出 182 种耐药表型(利福平 74 种、氨苯砜 87 种、氧氟沙星 21 种)。20 例显示利福平和氨苯砜耐药,4 例显示氧氟沙星和氨苯砜耐药,但没有利福平与氧氟沙星耐药的病例。在 12 个国家中,1143 例复发病例中有 58 例(5.1%)和 789 例新发病例中有 16 例(2.0%)出现利福平耐药。印度、巴西和哥伦比亚报告的利福平耐药病例超过 5 例。

结论

这是第一项报告全球麻风分枝杆菌 AMR 数据的研究。利福平耐药性的出现强调了扩大监测的必要性。这也呼吁警惕全球抗菌药物的使用,因为氧氟沙星耐药性可能与其他感染的抗生素常规使用有关,因为它不是用于治疗麻风病的多药联合用药的一部分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c24/6286419/b5805f683d9d/fx1.jpg

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