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최근 4년간 한 대학병원에서 분리된 Carbapenemase 생성 Enterobacteriaceae의 분자 역학과 특성 분석

Molecular Epidemiology and Characterization of Carbapenemase-Producing Enterobacteriaceae Isolated at a University Hospital in Korea during 4-Year Period

김현수|김명숙|박은숙|이경원|최준용|서영희|성지연|황연지|용동은|안선영|종소리|하은진
대한임상미생물학회 (Korean Society of Clinical Microbiology)|2016.06|Annals of Clinical Microbiology|제19권 제2호|pp. 39-47

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EnterobacteriaceaeKlebsiella pneumoniaeBeta-lactamase KPCCarbapenem resistance

초록

배경: Carbapenemase 생성 장내세균속(carbapenemase-producing Enterobacteriaceae, CPE)에 의한 감염증은 최근 10년간 전세계적으로 증가하였으며, 이러한 내성균에 의한 감염은 예후가 좋지 않고 전파 위험이 있어 감염 관리의 중요한 사안이되었다. CPE의 역학과 특성은 기관마다 다를 수 있기에 본 연구에서는 한 대학병원에서 최근 4년간 분리 동정된 CPE의분자역학 특성을 분석하였다. 방법: 2011년 10월부터 2015년 9월까지 세브란스병원의 임상 및 감시 배양 검체에서 분리된 CPE의 임상적 특성 및 항균제 감수성 결과를 분석하였다. Klebsiella pneumoniae carbapenemase (KPC) 생성 Klebsiella pneumoniae는 pulsed-field gel electrophoresis (PFGE)와 multilocus sequence typing (MLST)를 추가로 시행하였다. 결과: 연구기간 동안 carbapenem 내성 장내세균속은 총 222주가 분리되었고, 그 중 CPE는 25주(11%)였다. 가장 많은 수를 차지한 것은 KPC 생성 K. pneumonia였는데 2015년에 14주가 집중하여 분리되었고, 그 외 IMP-1형, VIM-2형, NDM-1 형, OXA-48형 CPE가 확인되었다. CPE의 carbapenem 최소억제농도(minimal inhibitory concentration, MIC)는 다양하였다. KPC 생성 K. pneumoniae는 ST307과 ST11이었고, PFGE에서는 시기별로 특정 clone의 outbreak를 시사하였다. 결론: 최근 4년간 본 기관에서 CPE 발생은 증가하였고, 가장 많은 균주는 KPC 생성 K. pneumoniae이었다. Carbapenem 내성 확산을 방지하기 위하여 CPE에 대한 지속적인 감시와 강화된 감염 관리가 필요하다.

Abstract

Background: Carbapenemase-producing Enterobacteriaceae (CPE) has been increasingly reported worldwide in the past 10 years, which is an important infection control concern. Since the epidemiology and characteristics of these CPEs vary according to institutes, we aimed to characterize CPEs in a university hospital during the recent 4 years. Methods: From October 2011 to September 2015, CPE isolates from clinical specimens and hospital surveillance cultures were collected. Carbapenem resistance was confirmed by disk diffusion method and Minimal Inhibitory Concentration (MIC) was determined by agar dilution method. Carbapenemase production was tested by double disk test using aminophenylboronic acid and dipicolic acid. PCR and sequence analysis were performed to detect blaKPC, blaIMP-1, blaVIM-2, blaNDM-1-like genes and blaOXA-48 gene. Pulsed-field gel electrophoresis (PFGE) and Multilocus sequence typing (MLST) were conducted for KPCproducing Klebsiella pneumoniae isolates. Results: Twenty-five isolates (11%) of CPE were identified among 222 carbapenem-resistant Enterobacteriacae isolates during the study period. The most prevalent CPE was KPC-producing K. pneumonia and others were IMP-1, VIM-2, NDM-1 type and OXA-48 producing CPEs. Most of these CPEs showed resistance to carbapenems with variable MICs. The sequence types (STs) of KPC-producing K. pneumoniae were ST307 and ST11. The PFGE of ST11 and ST307 showed clonality in each group suggesting the possibility of in-hospital outbreak. Conclusion: The prevalence of CPE has been increasing. In our institute, KPC-producing K. pneumoniae was the most frequently isolated CPE in the recent 4 years. CPE including KPC producers can easily transfer their resistance. Therefore continuous monitoring and more intensified infection control for CPE should be considered.

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