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Characteristics of Acquired β-lactamase Gene in Clinical Isolates of Multidrug-resistant Pseudomonas aeruginosa

박종우|신소연|성지연|송정훈|구선회|권계철|고지선|정선양
대한임상미생물학회 (Korean Society of Clinical Microbiology)|2008.10|Annals of Clinical Microbiology|제11권 제2호|pp. 98-106

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키워드

Multidrug resistancePseudomonas aeruginosaMetallo-β-lactamase (MBL)OXA type β-lactamase

초록

배경: 최근 cefepime이나 carbapenem계 항균제에도 내성을 보이는 다제내성 녹농균이 증가하고 있다. 저자들은 충청지역 에서 분리된 다제내성 녹농균을 대상으로 Ambler class A, B 그리고 D 에 속하는 β-lactamase와 그들의 광범위 활성 유도 체의 빈도를 조사하고 대표적인 유전형들을 규명하고자 하였다. 방법: 2006년 3월부터 2007년 5월까지 충남대학교 병원 환자의 임상검체에서 분리된 다제내성 녹농균을 대상으로 하였 다. Metallo-β-lactamase (MBL) 생성은 inhibitor-potentiated disk diffusion 시험으로 확인하였으며 Ambler Class A, B, 그리 고 D에 해당하는 β- lactamase 유전자를 검출하기 위해 중합연쇄반응과 염기서열 분석을 하였다. 또한 돌발감염이 있었 는지를 알아보기 위해서 enterobacterial repetitive intergenic consensus (ERIC)-PCR을 수행하였다. 결과: 시험기간 중 총 37주의 다제내성 녹농균이 환자의 임상검체에서 분리되었다. 37주의 녹농균 중 29주가 blaOXA-10 (56.8%), blaOXA-2 (18.9%), 또는 blaOXA-1 (5.4%)를 가지고 있는 것으로 나타났다. IMP-1을 생성하는 균주는 단 한 주였으며 blaOXA-1도 가지고 있었다. Ambler class A β-lactamase와 class D carbapenemase는 검출되지 않았다. OXA형 β-lactamase를 가지고 있는 균주의 경우 그렇지 않은 균주 보다 aminoglycoside계 항균제에 대한 내성율이 더 높은 것으로 나타났다. ERIC-PCR 결과 OXA-10을 생성하는 19주는 유전적으로 매우 밀접한 것으로 나타났다. 결론: 충청지역의 한 대학병원에서 분리된 다제내성 녹농균에 가장 광범위하게 확산되어 있는 획득성 β-lactamase는 OXA형 β-lactamase였다. 그리고 OXA형 β-lactamase를 갖고 있는 균주들은 β-lactam계 항균제뿐 아니라 aminoglycosie 계 항균제와 qunolone계 항균제등에 대해 내성 높은 내성율을 보였다.

Abstract

Background: Recently, there have been reports of infections with multidrug-resistant Pseudomonas aeruginosa. To determine the mechanism of the resistance, we investigated the prevalence of Ambler class A and D β-lactamases, their extended-spectrum derivatives, and class B and D carbapenemase in multidrug- resistant P. aeruginosa isolates. Methods: During the period of March 2006 to May 2007, clinical isolates of multidrug-resistant P. aeruginosa were collected from patients in Chungnam National University Hospital, Daejeon, Korea. Inhibitor- potentiated disk diffusion tests were used for the screening of metallo-β-lactamase (MBL) production. PCR and DNA sequencing were conducted for the detection of β-lactamase genes. We also employed the enterobacterial repetitive intergenic consensus (ERIC)- PCR method for an epidemiologic study. Results: A total of 37 consecutive, non-duplicate, multidrug-resistant P. aeruginosa were isolated. Twentynine of 37 isolates harbored blaOXA-10 (56.8%), blaOXA-2 (18.9%), and blaOXA-1 (5.4%). Only one isolate produced IMP-1, and it also harbored blaOXA-1. None harbored Ambler class A β-lactamase or class D carbapenemase. The strains producing OXA type β-lactamases showed a significantly higher resistance to aminoglycoside compared to non-producers. The ERIC-PCR pattern of the 19 OXA-10 producing strains indicated that the isolates were closely related in terms of clonality. Conclusion: OXA type β-lactamases are the most prevalent among the acquired β-lactamases produced by multidrug-resistant P. aeruginosa isolated at a university hospital in Chungcheong Province. Besides β-lactam antibiotics, the strains harboring OXA type β-lactamase showed a significantly higher resistance to aminoglycoside and qunolone.

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