OXA-23 혹은 IMP-1 β-Lactamase 생성 Acinetobacter baumannii에 의한 감염의 분자 역학
Molecular Epidemiology of Infection Caused by OXA-23 or IMP-1β-Lactamase-Producing Acinetobacter baumannii
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배경:본 연구에서는 부산의 한 종합병원에서 분리된 Acinetobacter baumannii를 대상으로 imipenem 내성현황을 조사하고 내성획득 기전을 규명하고자 하였다. 방법:2004년 6월에서 9월에 부산의 한 종합병원 환자의 임상검체에서 분리된 A. baumannii를 대상으로 하였다. 항균제 감수성은 디스크 확산법과 한천희석법으로 시험하였다. Carbapenemase와 metallo-β-lactamase 생성균주의 선별을 위하여 Hodge 변법과 EDTA-disk synergy 시험을 시행하였다. IMP, VIM 및 OXA형 유전자 검출을 위한 중합연쇄반응(polymerase chain reaction, PCR)을 시행하였으며, PCR 산물의 염기서열 분석을 통하여 유전형을 확인하였다. Isoelectric focusing으로 β-lactamase의 등전점을 측정하였으며, enterobacterial repetitive intergenic consensus (ERIC) PCR로 균주의 역학적 연관성을 조사하였다. 결과:시험기간 중 총 58주의 A. baumannii가 임상검체에서 분리되었으며, 이 중 14주 (24.1%)가 imipenem에 내성이었다. Imipenem 내성 14주 중 9주는 Hodge 변법에 양성이었으며, 이 중 2주는 EDTA-disk synergy법도 양성이었다. Hodge 변법에 양성인 7주는 blaOXA-23 유전자를 지니고 있었으며, 나머지 두주는 blaIMP-1 유전자를 지니고 있었다. OXA-23을 생성하는 7주와 IMP-1을 생성하는 2주는 ERIC PCR에서 각각 동일한 band 양상을 보였다. 결론:임상검체에서 분리된 A. baumannii 9주는 OXA-23 혹은 IMP-1 β-lactamase 생성에 의해서imipenem 내성을 획득하였음을 확인할 수 있었으며, ERIC PCR을 통하여 OXA-23과 IMP-1 생성 균주는 각각 동일감염원에서 유래되었음을 확인할 수 있었다.
Abstract
Background: The purposes of this study were to investigate the prevalence of imipenem-resistant clinical Acinetobacter baumanniiisolates and to determine the mechanism of the resistance. Methods: During the period of June to September 2004, susceptibility to imipenem of A. baumannii isolates from a hospital in Busan, Korea were investigated. The isolates were screened for the production of carbapenemase and metallo-β-lactamase by Modified-Hodge and EDTA-disk synergy tests, respectively; minimum inhibitory concentrations (MICs) were determined by agar dilution method. Genes coding for GES, IMP, VIM, SMP-1, GIM-1 and OXA type β-lactamases were searched by PCR amplification, and the PCR products were subjected to direct sequencing. Isoelectric points of β-lactamases were estimated by isoelectric focusing and the epidemiological relationships of isolates were investigated by enterobacterial repetitive intergenic consensus (ERIC) PCR. Results: Fifty eight strains of A. baumannii were isolated from clinical specimens during the surveillance period, and 14 isolates (24.1%) were resistant to imipenem. Of the 14 isolates, 9 were tested positive in Modified-Hodge test and 2 were also positive in EDTA-disk synergy test. Genes encoding OXA-23 and IMP-1 were detected in 7 and 2 isolates, respectively. In IEF studies, OXA-23 and IMP-1 enzymes had corresponding pIs at 6.7 and 9.0, respectively. Seven OXA-23-producing and 2 IMP-1-producing isolates showed the same ERIC PCR patterns. Conclusion: It is concluded that 7 and 2 A. baumannii isolates from the patients in a hospital in Busan acquired resistance to imipenem by producing OXA-23 and IMP-1 β-lactamases, respectively. The isolates producing these β-lactamases might be originated from a common source.
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