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侵袭性近平滑念珠菌复合体分离株的物种分布、唑类耐药性及相关分子机制:21 年来氟康唑耐药性的增加。

Species distribution, azole resistance and related molecular mechanisms in invasive Candida parapsilosis complex isolates: Increase in fluconazole resistance in 21 years.

机构信息

Medical Microbiology Department, Hacettepe University Faculty of Medicine, Ankara, Turkey.

出版信息

Mycoses. 2021 Aug;64(8):823-830. doi: 10.1111/myc.13296. Epub 2021 May 15.

DOI:10.1111/myc.13296
PMID:33934400
Abstract

BACKGROUND

Candida parapsilosis complex consists of three species, the prevalence and geographical distribution of which might vary. Increasing rates of fluconazole resistance among C. parapsilosis complex were reported from various centres.

OBJECTIVES

Aim of this study was to identify invasive C. parapsilosis complex strains up to species level, explore rates and molecular mechanisms of azole resistance and analyse temporal changes at a single centre.

METHODS

Isolates from blood cultures from 1997 to 2017 were included. Species were identified using RFLP of the SADH gene and confirmed with ITS sequencing when needed. In vitro susceptibility to fluconazole, voriconazole and posaconazole was tested and evaluated using EUCAST guidelines. Sequences of ERG11 and MRR1 genes were analysed for fluconazole non-susceptible isolates.

RESULTS

A total of 283 isolates from 181 patients were tested for azole susceptibility. All were C. parapsilosis sensu stricto, except one C. orthopsilosis. All three azoles were effective against 213 of the isolates from 135 patients, including one C. orthopsilosis. Fluconazole resistance was 13.3% (24/181 patients). While the first fluconazole-resistant isolates were detected in 2004, increase was evident after 2011. In ERG11, Y132F mutation was the most common among fluconazole non-susceptible isolates (71.7%), followed by G458S (10.9%) and D421N (4.3%). In MRR1, R405K (56.5%) and G927C (8.7%) were detected. However, association of these mutations to azole resistance is yet to be investigated.

CONCLUSIONS

Rising azole resistance rates in C. parapsilosis sensu stricto isolates particularly after 2011 were of concern. The well-known Y132F mutation was the predominant mechanism of azole resistance while accompanied with other genetic mutations.

摘要

背景

近平滑念珠菌复合体由三个物种组成,其流行和地理分布可能有所不同。从不同中心报告称,近平滑念珠菌复合体中氟康唑耐药率不断增加。

目的

本研究旨在鉴定至种水平的侵袭性近平滑念珠菌复合体菌株,探讨唑类耐药的发生率和分子机制,并分析单一中心的时间变化。

方法

纳入了 1997 年至 2017 年血培养的分离株。使用 SADH 基因的 RFLP 鉴定物种,并在需要时使用 ITS 测序进行确认。使用 EUCAST 指南测试和评估氟康唑、伏立康唑和泊沙康唑的体外药敏性。分析氟康唑非敏感性分离株中 ERG11 和 MRR1 基因的序列。

结果

对来自 181 名患者的 283 株分离株进行了唑类药物敏感性测试。除一株近平滑念珠菌外,所有分离株均为近平滑假丝酵母。三种唑类药物均对来自 135 名患者的 213 株分离株有效,其中包括一株近平滑假丝酵母。氟康唑耐药率为 13.3%(181 名患者中有 24 名)。虽然第一个氟康唑耐药分离株于 2004 年被检测到,但自 2011 年以来耐药率明显增加。在 ERG11 中,Y132F 突变是氟康唑非敏感性分离株中最常见的突变(71.7%),其次是 G458S(10.9%)和 D421N(4.3%)。在 MRR1 中,检测到 R405K(56.5%)和 G927C(8.7%)。然而,这些突变与唑类耐药的相关性尚待研究。

结论

尤其自 2011 年以来,近平滑假丝酵母敏感株中唑类耐药率的上升令人担忧。众所周知的 Y132F 突变是唑类耐药的主要机制,同时伴有其他遗传突变。

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