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在没有选择压力的情况下出现喹诺酮类药物耐药:亚马逊森林中一个非常偏远社区的经验。

Quinolone resistance in absence of selective pressure: the experience of a very remote community in the Amazon forest.

机构信息

Dipartimento di Biotecnologie, Sezione di Microbiologia, Università di Siena, Siena, Italy.

出版信息

PLoS Negl Trop Dis. 2012;6(8):e1790. doi: 10.1371/journal.pntd.0001790. Epub 2012 Aug 28.

Abstract

BACKGROUND

Quinolones are potent broad-spectrum bactericidal agents increasingly employed also in resource-limited countries. Resistance to quinolones is an increasing problem, known to be strongly associated with quinolone exposure. We report on the emergence of quinolone resistance in a very remote community in the Amazon forest, where quinolones have never been used and quinolone resistance was absent in 2002.

METHODS

The community exhibited a considerable level of geographical isolation, limited contact with the exterior and minimal antibiotic use (not including quinolones). In December 2009, fecal carriage of antibiotic resistant Escherichia coli was investigated in 120 of the 140 inhabitants, and in 48 animals reared in the community. All fluoroquinolone-resistant isolates were genotyped and characterized for the mechanisms of plasmid- and chromosomal-mediated quinolone resistance.

PRINCIPAL FINDINGS

Despite the characteristics of the community remained substantially unchanged during the period 2002-2009, carriage of quinolone-resistant E. coli was found to be common in 2009 both in humans (45% nalidixic acid, 14% ciprofloxacin) and animals (54% nalidixic acid, 23% ciprofloxacin). Ciprofloxacin-resistant isolates of human and animal origin showed multidrug resistance phenotypes, a high level of genetic heterogeneity, and a combination of GyrA (Ser83Leu and Asp87Asn) and ParC (Ser80Ile) substitutions commonly observed in fluoroquinolone-resistant clinical isolates of E. coli.

CONCLUSIONS

Remoteness and absence of antibiotic selective pressure did not protect the community from the remarkable emergence of quinolone resistance in E. coli. Introduction of the resistant strains from antibiotic-exposed settings is the most likely source, while persistence and dissemination in the absence of quinolone exposure is likely mostly related with poor sanitation. Interventions aimed at reducing the spreading of resistant isolates (by improving sanitation and water/food safety) are urgently needed to preserve the efficacy of quinolones in resource-limited countries, as control strategies based only on antibiotic restriction policies are unlikely to succeed in those settings.

摘要

背景

喹诺酮类药物是一种强效广谱杀菌药物,在资源有限的国家也越来越多地使用。对喹诺酮类药物的耐药性是一个日益严重的问题,已知与喹诺酮类药物的暴露有很强的相关性。我们报告了在亚马逊雨林一个非常偏远的社区中出现的喹诺酮类耐药性,该社区从未使用过喹诺酮类药物,并且在 2002 年也没有出现喹诺酮类耐药性。

方法

该社区地理位置非常孤立,与外界接触有限,抗生素使用量也很少(不包括喹诺酮类药物)。2009 年 12 月,对 140 名居民中的 120 人和社区内饲养的 48 只动物进行了粪便中携带抗生素耐药性大肠杆菌的调查。所有氟喹诺酮类耐药分离株均进行了基因分型,并对质粒和染色体介导的喹诺酮类耐药机制进行了特征描述。

主要发现

尽管 2002 年至 2009 年期间社区的特征基本保持不变,但 2009 年人类(萘啶酸 45%,环丙沙星 14%)和动物(萘啶酸 54%,环丙沙星 23%)中均发现携带喹诺酮类耐药大肠杆菌的情况很常见。来自人类和动物来源的环丙沙星耐药分离株表现出多药耐药表型、高度的遗传异质性,以及氟喹诺酮类耐药大肠杆菌临床分离株中常见的 GyrA(Ser83Leu 和 Asp87Asn)和 ParC(Ser80Ile)取代的组合。

结论

偏远和缺乏抗生素选择压力并不能保护社区免受大肠杆菌中喹诺酮类耐药性的显著出现。来自抗生素暴露环境的耐药菌株的引入是最有可能的来源,而在没有喹诺酮类药物暴露的情况下,耐药菌株的持续存在和传播可能主要与卫生条件差有关。迫切需要采取干预措施减少耐药分离株的传播(通过改善卫生和水/食品安全),以维护资源有限国家中喹诺酮类药物的疗效,因为仅基于抗生素限制政策的控制策略在这些环境中不太可能成功。

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