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希腊某大学医院产碳青霉烯酶肺炎克雷伯菌β-内酰胺酶 2 的肺炎克雷伯菌感染暴发:分子特征、流行病学和结局。

An outbreak of infection due to beta-Lactamase Klebsiella pneumoniae Carbapenemase 2-producing K. pneumoniae in a Greek University Hospital: molecular characterization, epidemiology, and outcomes.

机构信息

4th Dept of Internal Medicine, University General Hospital ATTIKON, 1 Rimini Str 124 62, Chaidari, Greece.

出版信息

Clin Infect Dis. 2010 Feb 1;50(3):364-73. doi: 10.1086/649865.

Abstract

BACKGROUND

We describe the emergence and spread of Klebsiella pneumoniae carbapenemase 2 (KPC-2)-producing K. pneumoniae at a Greek University hospital.

METHODS

Isolates with a carbapenem minimum inhibitory concentration >1 microg/mL and a negative EDTA-imipenem disk synergy test result were submitted to boronic acid disk test and to polymerase chain reaction (PCR) for KPC gene and sequencing. Records from patients who had KPC-2-producing K. pneumoniae isolated were retrospectively reviewed. Clinical isolates were submitted to molecular typing using pulsed-field gel electrophoresis, and the beta-lactamase content was studied using isoelectric focusing and PCR.

RESULTS

From January 2007 through December 2008, 50 patients (34 in the intensive care unit [ICU]) were colonized (n = 32) or infected (n = 18) by KPC-2-producing K. pneumoniae. Increasing prevalence of KPC-2-producing K. pneumoniae coincided with decreasing prevalence of metallo-beta lactamase-producing isolates in our ICU. Multidrug resistance characterized the studied isolates, with colistin, gentamicin, and fosfomycin being the most active agents. Besides KPC-2, clinical isolates encoded TEM-1-like, SHV-11, SHV-12, CTX-M-15, and LEN-19 enzymes. Four different clonal types were detected; the predominant one comprised 41 single patient isolates (82%). Sporadic multiclonal cases of KPC-2-producing K. pneumoniae infection were identified from September 2007 through May 2008. The outbreak strain was introduced in February 2008 and disseminated rapidly by cross-transmission; 38 patients (76%) were identified after August 2008. Fourteen cases of bacteremia, 2 surgical site infections, 2 lower respiratory tract infections (1 bacteremic), and 1 urinary tract infection were identified. Most patients received a colistin-containing combination treatment. Crude mortality was 58.8% among ICU patients and 37.5% among non-ICU patients, but attributable mortality was 22.2% and 33.3%, respectively.

CONCLUSIONS

The emergence of KPC-2-producing K. pneumoniae in Greek hospitals creates an important challenge for clinicians and hospital epidemiologists, because it is added to the already high burden of antimicrobial resistance.

摘要

背景

我们描述了希腊一家大学医院出现和传播产碳青霉烯酶 2 (KPC-2) 的肺炎克雷伯菌。

方法

对碳青霉烯类药物最低抑菌浓度(MIC)>1μg/mL,EDTA-亚胺培南纸片协同试验结果阴性的分离株进行硼酸纸片试验和聚合酶链反应(PCR)检测 KPC 基因和测序。回顾性分析了分离出产 KPC-2 肺炎克雷伯菌的患者的病历记录。采用脉冲场凝胶电泳对临床分离株进行分子分型,采用等电聚焦和 PCR 研究β-内酰胺酶含量。

结果

2007 年 1 月至 2008 年 12 月,50 例(34 例在重症监护病房[ICU])患者定植(32 例)或感染(18 例)产 KPC-2 的肺炎克雷伯菌。KPC-2 产肺炎克雷伯菌的流行率增加与 ICU 中金属β-内酰胺酶产菌株的流行率降低同时发生。研究分离株表现出多药耐药性,多粘菌素、庆大霉素和磷霉素是最有效的药物。除 KPC-2 外,临床分离株还编码 TEM-1 样、SHV-11、SHV-12、CTX-M-15 和 LEN-19 酶。共检测到 4 种不同的克隆类型,主要类型包括 41 例单例患者分离株(82%)。2007 年 9 月至 2008 年 5 月,发现了散发的多克隆产 KPC-2 肺炎克雷伯菌感染病例。2008 年 2 月,暴发菌株传入并迅速通过交叉传播扩散;2008 年 8 月后共发现 38 例患者(76%)。14 例菌血症、2 例手术部位感染、2 例下呼吸道感染(1 例菌血症)和 1 例尿路感染。大多数患者接受了含多粘菌素的联合治疗。ICU 患者的粗死亡率为 58.8%,非 ICU 患者为 37.5%,但归因死亡率分别为 22.2%和 33.3%。

结论

产 KPC-2 肺炎克雷伯菌在希腊医院的出现给临床医生和医院流行病学家带来了重要挑战,因为它增加了已经很高的抗菌药物耐药性负担。

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