2006년 서울과 경기지역 4개 병원에서 분리된 Carbapenem 내성 Acinetobacter spp.의 내성 기전과 분자역학
Carbapenem Resistance Mechanisms and Molecular Epidemiology of Acinetobacter spp. from Four Hospitals in Seoul and Gyeonggi Province in 2006
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배경: 최근 carbapenem을 포함한 다약제 내성 Acinetobacter spp.가 증가하고 있어 심각한 문제가 되고 있다. 본 연구에서는 국내 4개 병원에서 분리되는 Acinetobacter spp.의 항균제 내성 양상과 carbapenem 내성 기전 및 분자역학적 성상을규명하고자 하였다. 방법: 2006년 5월에서 11월까지 서울의 세 지역과 경기의 한 지역에 위치한 4개 중대형병원 환자에서 분리된Acinetobacter spp. 균주를 수집하였다. CLSI 디스크 확산법과 한천희석법으로 항균제 감수성을 시험하였고, PCR 검사로metallo-β-lactamase와 OXA형 carbapenemase 생성균을 검출하였다. OXA형과 ISAba1의 유무에 따른 carbapenem 내성과가수분해능을 비교하였고, OXA형 carbapenemase 생성균의 염색체 DNA의 pulsed-field gel electrophoresis (PFGE) 성상을분석하였다. 결과: Acinetobacter spp.의 carbapenem 비감수성률은 10∼67%로 일부 병원에서 이미 높았다. OXA carbapenemase를 생성하는 151주는 ISAb1이 없는 blaOXA-51형 51주, ISAba1 동시양성인 blaOXA-51형 75주, ISAba1, blaOXA-51과 blaOXA-23 동시 양성인 균주 25주로 구성되어 있었다. blaOXA-51형 중 ISAba1이 존재하는 균주가 carbapenem MIC가 높았으며, blaOXA-51 단독존재보다 blaOXA-23 동시 존재 균주가 carbapenem MIC가 높았다. 가수분해 활성도 측정에서도 blaOXA-51형 중 ISAba1이 존재하는 균주와 blaOXA-23가 동시 존재 균주가 oxacillin에 강한 분해활성을 보였고, carbapenem에 대해서도 상대적인 활성도가 높았다 Tigecycline에는 대부분의 시험균주가, colistin에는 시험 균주 모두가 감수성이었다. PFGE분석으로 blaOXA-23형과 blaOXA-51형 유전자 양성 균주에 의한 집단발생이 흔함을 알 수 있었다. 결론: 국내 분리 Acinetobacter spp. 중에 carbapenem 내성균주와 OXA형 carbapenemase 생성 균주는 매우 흔하였고 병원내 집단 발생이 종종 있음을 추정할 수 있었다. OXA형 carbapenemase 생성 균주의 확산은 carbapenem 내성 Acinetobacter spp.에 의한 감염증 치료를 어렵게 할 것이므로 이에 대한 향후 대책이 시급할 것으로 생각한다. [대한임상미생물학회지2010;13:27-33]
Abstract
Background: Increasing numbers of Acinetobacter spp. resistant to multiple drugs, including carbapenem,has been a serious problem. The aims of this study were to determine carbapenem resistance patterns and mechanisms, as well as to study the molecular epidemiology of Acinetobacter spp. Methods: Clinical isolates of Acinetobacter spp. were collected from May to November in 2006. Antimicrobial susceptibility testing was performed using CLSI disk diffusion and agar dilution methods. Metallo-β-lactamase- and OXA carbapenemase-producing isolates were detected by PCR. Carbapenem resistance and hydrolytic activities were compared according to OXA type and presence of ISAba1. Pulsed-field gel electrophoresis (PFGE) was performed to determine the epidemiologic features. Results: The imipenem non-susceptible rates were variable from 10% to 67%. Among 151 isolates carrying blaOXA-51-like, 75 isolates carried both blaOXA-51-like and ISAba1, and 25 isolates had both blaOXA-51-like,blaOXA-23-like, and ISAba1. Carbapenem MICs of both blaOXA-51-like and ISAba1-carrying isolates were higher than those with blaOXA-51-like only. Carbapenem MICs of blaOXA-23-like-carrying isolates were higher than those with both blaOXA-51-like and ISAba1. Both blaOXA-51-like and ISAba1-carrying isolates and blaOXA-51-like, blaOXA-23-like,and ISAba1-carrying isolates demonstrated higher hydrolysis activities in oxacillin and carbapenems. Most of the tested isolates were susceptible to tigecycline,and all of them were susceptible to colistin. Pulsed-field gel electrophoresis suggested that there had been several outbreaks of blaOXA-23-like and blaOXA-51-like-positive strains. Conclusion: Carbapenem non-susceptible Acinetobacter isolates and OXA carbapenemase-producing isolates were prevalent. Dissemination of blaOXA-harboring isolates may make it difficult to treat infections due to carbapenem-resistant Acinetobacter spp. Further surveillance studies are required to prevent the spread of carbapenem resistance. (Korean J Clin Microbiol 2010;13:27-33)
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