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

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

  • Yum, Jong Hwa (Department of Clinical Laboratory Science, Dongeui University)
  • Received : 2019.09.22
  • Accepted : 2019.10.08
  • Published : 2019.12.31

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.

주요 획득성 metallo-β-lactamase (MBL) 유전자에 의해 매개되는 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%)주가 imipenem-EDTA+SMA double disk synergy (DDS) 시험에 양성이었다. blaVIM-2 allele와 blaIMP-2 allele 검출을 위한 중합효소연쇄반응과 염기서열분석을 시행한 결과, A. baumannii와 A. calcoaceticus에서 각각 29주와 1주가 blaVIM-2를 갖고 있었고, A. baumannii 16주와 A. calcoaceticus 2주가 blaIMP-1을 갖고 있었다. A. genomospecies 3는 blaVIM-2와 blaAIM-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 kb에서 3.2 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 integron의 전파로 imipenem이나 meropenem과 같은 carbapenem 내성을 포함하여 다제 내성 그람음성 세균의 증가가 예상된다. 또한, 위중한 Acinetobacter spp. 감염증 치료를 위한 새로운 항균제 개발이 필요하다.

Keywords

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