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국내 대학병원에서 분리된 Metallo-β-Lactamase (MBL) 생성 Acinetobacter spp. 분리주의 높은 출현율과 유전형 특징

High Prevalence and Genotypic Characterization of Metallo-β-Lactamase (MBL)-Producing Acinetobacter spp. Isolates Disseminated in a Korean Hospital

염종화
대한임상검사과학회 (Korean Society for Clinical Laboratory Science)|2019.12|대한임상검사과학회지 (Korean Journal of Clinical Laboratory Science)|제51권 제4호|pp. 444-452|DOI 10.15324/kjcls.2019.51.4.444

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키워드

Acinetobacter spp.blaIMP-6blaVIM-2Carbapenem resistant Metallo-β-lactamase
주제분류기타자연과학

초록

주요 획득성 metallo--lactamase (MBL) 유전자에 의해매개되는 carbapenem 내성, 특히 Acinetobacter spp. 균종의 임상 분리주에 대한 보고가 증가하고 있다. 본 연구에서 임상에서 비 중복으로 분리된 carbapenem 비감수성 Acinetobacter spp. 191주 중 125 (65.4%)주가 imipenem 혹은 meropenem- Hodge 변법시험에 양성이었고, 49 (25.7%)주가imipenem-EDTA+SMA double disk synergy (DDS) 시험에 양성이었다. blaVIM-2 allele와 blaIMP-2 allele 검출을 위한 중합효소연쇄반응과 염기서열분석을 시행한 결과, A. baumannii 와 A. calcoaceticus에서 각각 29주와 1주가 blaVIM-2를 갖고있었고, A. baumannii 16주와 A. calcoaceticus 2주가blaIMP-1을 갖고 있었다. A. genomospecies 3는 blaVIM-2와blaAIM-1을 동시에 갖고 있었다. 이들 MBL 유전자는 모두 class 1 integron에 있었다. blaVIM-2 혹은 blaIMP-6를 갖는 class 1 integron의 크기는 A. baumannii 분리주에서는 2.8 kb에서3.2 kb이었고, A. genomospecies 3 분리주에서는 3.2 kb에서 3.5 kb이었다. blaVIM-2는 대부분 class 1 integron에 첫번째 혹은 두번째에 위치하였고, aacA4를 흔히 가지고 있었다. 다양한 내성 유전자를 가질 수 있는 MBL 생성 Acinetobacter spp.뿐 아니라 다양한 내성 유전자를 가질 수 있는 integron의전파로 imipenem이나 meropenem과 같은 carbapenem 내성을 포함하여 다제 내성 그람음성 세균의 증가가 예상된다. 또한, 위중한 Acinetobacter spp. 감염증 치료를 위한 새로운항균제 개발이 필요하다.

Abstract

Carbapenem resistance, mediated by the major acquired metallo-β-lactamase (MBL) genes, has been increasingly reported, particularly for clinical isolates of Acinetobacter spp. Of the 191 nonduplicate clinical isolates of the carbapenem-nonsusceptible Acinetobacter spp. evaluated, 125 isolates (65.4%) were positive for the modified imipenem or meropenem-Hodge test, and 49 isolates (25.7%) were positive for the imipenem-EDTA+SMA double disk synergy test (DDS). PCR and sequencing of the blaVIM-2-allele and blaIMP-1-allele showed that 29 A. baumannii isolates and 1 A. calcoaceticus isolate had blaVIM-2, whereas 16 A. baumannii isolates and 2 A. calcoaceticus isolates had blaIMP-6; 1 isolate of the A. genomospecies 3 had blaVIM-2 and blaAIM-1. All the above MBL genes belong to class 1 integron. The size of class 1 integron encompassing blaVIM-2 or blaIMP-6 ranges from 2.8 kb to 3.2 kb in clinical isolates of A. baumannii, and 3.2 kb to 3.5 kb in clinical isolates of A.genomospecies 3. blaVIM-2 was most often located first or second in the class 1 integron, and these integrons often included aacA4. Due to dispersion of the MBL-producing Acinetobacter spp. as well as integron, which may encompass various resistance genes, there is an expectation for the increase of multidrug resistant Gram-negative bacteria, including resistance of carbapenems such as imipenem or meropenem. Hence, the development of new antimicrobial agents for treating severe Acinetobacter spp. infections is needed.

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1·2차 의료기관 임상 검체에서 분리된 Acinetobacter spp.의 항균제 내성과 Metallo-β-Lactamase 생성주 검출김봉수, 유용선, 유재일, 이영선, 이점규대한감염학회 · Infection and Chemotherapy2004 · 제36권 제5호Pseudomonas aeruginosa 와 Acinetobacter baumannii 에서의 Metallo-β-lactamase의 유병률김재룡, 류남희, 전동석, 하정숙대한임상미생물학회 · Annals of Clinical Microbiology2010 · 제13권 제4호Metallo-β-lactamase 생성 녹농균에서 Class 1 Integron의 유전형 분석고지선, 구선회, 권계철, 박종우, 성지연, 송정훈, 신소연대한임상미생물학회 · Annals of Clinical Microbiology2009 · 제12권 제1호한 대학병원에서 다년간 수집된 Imipenem 내성 Acinetobacterbaumannii와 Pseudomonas aeruginosa의 Carbapenemase와Integrase 내성유전자 보유율박건, 김원용, 문대수, 박영진, 신성희, 오혜룡, 유봉남, 이학민, 장숙진대한임상미생물학회 · Annals of Clinical Microbiology2007 · 제10권 제2호IMP-1과 OXA -lactamase를 생성하는 Carbapenem 내성 Acinetobacter baumanni 의 확산고지선, 구선회, 권계철, 김연숙, 김종완, 김지명, 박종우, 성지연, 송정훈, 신경섭, 신소연대한진단검사의학회 · Annals of Laboratory Medicine2008 · 제28권 제1호2006년 서울과 경기지역 4개 병원에서 분리된 Carbapenem 내성 Acinetobacter spp.의 내성 기전과 분자역학김창기, 노경호, 염종화, 용동은, 이경원, 이창규, 임채승, 정석훈, 정윤섭, 조윤정대한임상미생물학회 · Annals of Clinical Microbiology2010 · 제13권 제1호

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