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医院内氟康唑耐药性的暴发:克隆传播及长期持续存在的证据

Hospital outbreak of fluconazole-resistant : arguments for clonal transmission and long-term persistence.

作者信息

Fekkar Arnaud, Blaize Marion, Bouglé Adrien, Normand Anne-Cécile, Raoelina Audrey, Kornblum Dimitri, Kamus Laure, Piarroux Renaud, Imbert Sébastien

机构信息

AP-HP, Groupe Hospitalier La Pitié-Salpêtrière, Service de Parasitologie Mycologie, Paris, France

Sorbonne Université, Inserm, CNRS, Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France.

出版信息

Antimicrob Agents Chemother. 2023 May 1;95(5). doi: 10.1128/AAC.02036-20. Epub 2021 Feb 16.

Abstract

The worldwide emergence of multidrug-resistant pathogenic fungi is a threat to human health. At this very moment, an emergence of isolates harbouring a resistance to fluconazole, one of the most popular antifungal drugs, is being described in several countries. We seek to better understanding the epidemiology, pathogenicity and transmission of resistant Faced with an outbreak of invasive infections due to resistant isolates of , we performed a 7-year retrospective and prospective analysis of 283 isolates collected in 240 patients, among who 111 had invasive candidiasis. Study included review of hospital records, genotyping analysis and susceptibility testing that allow determining the type and outcome of infections, as well as the spatial and temporal spread of clusters. Overall the incidence of azole resistance was 7.5%. Genotyping analysis unveiled several previously undetected outbreaks and clonal spread of susceptible and resistant isolates over a long period of time. In comparison with susceptible isolates, resistant ones have a more restricted genetic diversity and seem to be more likely to spread and more frequently associated with invasive infections. In intensive care units, patients with invasive infections due to resistant isolates had poorer outcome (overall mortality at day 30 of 40%; 4/10) than susceptible ones (overall mortality at day 30 of 26.5%; 9/34). Our results suggest that the propensity of to spread on an epidemic fashion is underestimated, which warrants reinforced control and epidemiological survey of this species.

摘要

多重耐药致病真菌在全球范围内的出现对人类健康构成威胁。此时此刻,在多个国家都有报道称出现了对最常用的抗真菌药物之一氟康唑耐药的分离株。我们试图更好地了解耐药菌的流行病学、致病性和传播情况。面对耐药分离株引起的侵袭性感染暴发,我们对240例患者中收集的283株念珠菌分离株进行了为期7年的回顾性和前瞻性分析,其中111例患有侵袭性念珠菌病。研究包括查阅医院记录、基因分型分析和药敏试验,以确定感染的类型和结果,以及菌群的时空传播。总体而言,唑类耐药的发生率为7.5%。基因分型分析揭示了几起以前未被发现的暴发以及敏感和耐药分离株在很长一段时间内的克隆传播。与敏感分离株相比,耐药分离株的遗传多样性更有限,似乎更有可能传播,并且更频繁地与侵袭性感染相关。在重症监护病房,由耐药分离株引起侵袭性感染的患者预后比敏感患者差(30天时的总体死亡率为40%;4/10)(敏感患者30天时的总体死亡率为26.5%;9/34)。我们的结果表明,念珠菌以流行方式传播的倾向被低估了,这就需要加强对该菌种的控制和流行病学调查。

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