OXA-48 型β-内酰胺酶在克罗地亚的流行传播。

Epidemic spread of OXA-48 beta-lactamase in Croatia.

机构信息

1School of Medicine, University of Zagreb, Croatia.

2University Hospital Center Zagreb, Croatia.

出版信息

J Med Microbiol. 2018 Aug;67(8):1031-1041. doi: 10.1099/jmm.0.000777. Epub 2018 Jun 21.

DOI:10.1099/jmm.0.000777

PMID:29927373

Abstract

PURPOSE

A dramatic increase in OXA-48 β-lactamase was observed recently not only in large hospital centres, but also in smaller suburban hospital centres in geographic areas bordering Croatia. The aim of the study was to analyse the epidemiology, the mechanisms of antibiotic resistance and the routes of spread of OXA-48 carbapenemase in Croatia.

METHODS

Carbapenemase and other β-lactamase and fluoroquinolone resistance genes were detected by PCR and sequencing. Whole-genome sequencing (WGS) was performed on five representative isolates. The isolates were genotyped by PFGE.

RESULTS

Forty-eight isolates positive for OXA-48, collected from seven hospital centres in Croatia from May 2016 to May 2017, were analysed (40 Klebsiella pneumoniae, 5 Enterobacter cloacae, 2 Escherichia coli and one Citrobacter freundii). Thirty-three isolates were ESBL positive and harboured group 1 CTX-M 1 β-lactamases. In addition to the β-lactam resistance genes detected by PCR (blaSHV-1, blaOXA-48 and blaOXA-1), WGS of five representative isolates revealed the presence of genes encoding aminoglycoside resistance, aadA2 and aph3-Ia, fluoroquinolone resistance determinants aac(6)Ib-c, oqxA and oqxB, the sulfonamide resistance gene sul1, and fosA (fosfomycin resistance). IncL plasmid was found in all isolates. Two K. pneumoniae isolates belonged to ST16, two E. cloacae to ST66 and E. coli to ST354. K. pneumoniae isolates were allocated to five clusters by PFGE which occured in different hospitals, indicating epidemic spread.

CONCLUSIONS

The OXA-48-positive organisms found in this study showed wide variability in antibiotic susceptibility, β-lactamase content and PFGE banding patterns. This study revealed a switch from the predominance of VIM-1 in 2012-2013 to that of OXA-48 in the 2015 to 2017.

摘要

目的

最近不仅在大型医院中心，而且在与克罗地亚接壤的地理区域的较小郊区医院中心，都观察到 OXA-48β-内酰胺酶急剧增加。本研究的目的是分析 OXA-48 碳青霉烯酶在克罗地亚的流行病学、抗生素耐药机制和传播途径。

方法

通过 PCR 和测序检测碳青霉烯酶和其他β-内酰胺酶和氟喹诺酮耐药基因。对 5 个代表性分离株进行全基因组测序（WGS）。通过 PFGE 对分离株进行基因分型。

结果

从 2016 年 5 月至 2017 年 5 月，在克罗地亚的七个医院中心收集了 48 株对 OXA-48 呈阳性的分离株（40 株肺炎克雷伯菌、5 株阴沟肠杆菌、2 株大肠埃希菌和 1 株弗氏柠檬酸杆菌）。33 株分离株为 ESBL 阳性，携带组 1 CTX-M 1β-内酰胺酶。除了通过 PCR 检测到的β-内酰胺耐药基因（blaSHV-1、blaOXA-48 和 blaOXA-1）外，对 5 个代表性分离株的 WGS 显示存在编码氨基糖苷类耐药基因 aadA2 和 aph3-Ia、氟喹诺酮耐药决定子 aac(6)Ib-c、oqxA 和 oqxB、磺胺类耐药基因 sul1 和 fosA（磷霉素耐药）的基因。所有分离株均发现 IncL 质粒。2 株肺炎克雷伯菌分离株属于 ST16，2 株阴沟肠杆菌属于 ST66，1 株大肠埃希菌属于 ST354。PFGE 将 2 株肺炎克雷伯菌分离株分为 5 个簇，这些簇发生在不同的医院，表明存在流行传播。