意大利血液病患者监测培养曲霉菌株中唑类耐药性的前瞻性多中心研究。

Prospective multicentre study on azole resistance in Aspergillus isolates from surveillance cultures in haematological patients in Italy.

作者信息

Prigitano A, Esposto M C, Grancini A, Passera M, Paolucci M, Stanzani M, Sartor A, Candoni A, Pitzurra L, Innocenti P, Micozzi A, Cascio G Lo, Delia M, Mosca A, Mikulska M, Ossi C, Fontana C, Pizzolante M, Gelmi M, Cavanna C, Lallitto F, Amato G, Vella A, Pagano L, Bandettini R, De Lorenzis G, Cogliati M, Romanò L, Tortorano A

机构信息

Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy.

出版信息

J Glob Antimicrob Resist. 2020 Sep;22:231-237. doi: 10.1016/j.jgar.2020.01.016. Epub 2020 Feb 13.

DOI:10.1016/j.jgar.2020.01.016

PMID:32061880

Abstract

OBJECTIVES

This study was conducted to assess the prevalence of azole resistance in Aspergillus isolates from patients with haematological malignancies or who were undergoing haematopoietic stem cell transplantation and to identify the molecular mechanism of resistance.

METHODS

In this 28-month prospective study involving 18 Italian centres, Aspergillus isolates from surveillance cultures were collected and screened for azole resistance, and mutations in the cyp51A gene were identified. Resistant isolates were genotyped by microsatellite analysis, and the allelic profiles were compared with those of resistant environmental and clinical isolates from the same geographical area that had been previously genotyped.

RESULTS

There were 292 Aspergillus isolates collected from 228 patients. The isolates belonged mainly to the section Fumigati (45.9%), Nigri (20.9%), Flavi (16.8%) and Terrei (4.8%). Three isolates showed itraconazole resistance: Aspergillus fumigatus sensu stricto, Aspergillus lentulus (section Fumigati) and Aspergillus awamori (section Nigri). The itraconazole resistance rates were 1% and 1.48% considering all Aspergillus spp. isolates and the Aspergillus section Fumigati, respectively. The prevalence of azole resistance among all the patients was 1.3%. Among patients harbouring A. fumigatus sensu stricto isolates, the resistance rate was 0.79%. The A. fumigatus isolate, with the TR/L98H mutation, was genotypically distant from the environmental and clinical strains previously genotyped.

CONCLUSIONS

In this study, the Aspergillus azole resistance rate was 1% (3/292). In addition to A. fumigatus sensu stricto, A. lentulus and A. awamori azole-resistant isolates were identified. Therefore, it is important have a correct identification at the species level to address a rapid therapy better, quickly understand the shift towards cryptic species and have an updated knowledge of the local epidemiology.

摘要

目的

本研究旨在评估血液系统恶性肿瘤患者或接受造血干细胞移植患者曲霉菌分离株中唑类耐药的发生率，并确定耐药的分子机制。

方法

在这项涉及18个意大利中心的为期28个月的前瞻性研究中，收集监测培养物中的曲霉菌分离株并筛选唑类耐药性，同时鉴定cyp51A基因中的突变。通过微卫星分析对耐药分离株进行基因分型，并将等位基因谱与先前已进行基因分型的来自同一地理区域的耐药环境和临床分离株的等位基因谱进行比较。

结果

从228例患者中收集到292株曲霉菌分离株。这些分离株主要属于烟曲霉组（45.9%）、黑曲霉组（20.9%）、黄曲霉组（16.8%）和土曲霉组（4.8%）。三株分离株显示对伊曲康唑耐药：狭义烟曲霉、勒图曲霉（烟曲霉组）和泡盛曲霉（黑曲霉组）。考虑所有曲霉菌种分离株和烟曲霉组时，伊曲康唑耐药率分别为1%和1.48%。所有患者中唑类耐药的发生率为1.3%。在携带狭义烟曲霉分离株的患者中，耐药率为0.79%。具有TR/L98H突变的烟曲霉分离株在基因分型上与先前已进行基因分型的环境和临床菌株不同。