Senda K, Arakawa Y, Nakashima K, Ito H, Ichiyama S, Shimokata K, Kato N, Ohta M
Department of Bacteriology, Nagoya University School of Mecicine, Japan.
Antimicrob Agents Chemother. 1996 Feb;40(2):349-53. doi: 10.1128/AAC.40.2.349.
A total of 3,700 Pseudomonas aeruginosa isolates were collected from 17 general hospitals in Japan from 1992 to 1994. Of these isolates, 132 carbapenem-resistant strains were subjected to DNA hybridization analysis with the metallo-beta-lactamase gene (blaIMP)-specific probe. Fifteen strains carrying the metallo-beta-lactamase gene were identified in five hospitals in different geographical areas. Three strains of P. aeruginosa demonstrated high-level imipenem resistance (MIC, > or = 128 micrograms/ml), two strains exhibited low-level imipenem resistance (MIC, < or = 4 micrograms/ml), and the rest of the strains were in between. These results revealed that the acquisition of a metallo-beta-lactamase gene alone does not necessarily confer elevated resistance to carbapenems. In several strains, the metallo-beta-lactamase gene was carried by large plasmids, and carbapenem resistance was transferred from P. aeruginosa to Escherichia coli by electroporation in association with the acquisition of the large plasmid. Southern hybridization analysis and genomic DNA fingerprinting profiles revealed different genetic backgrounds for these 15 isolates, although considerable similarity was observed for the strains isolated from the same hospital. These findings suggest that the metallo-beta-lactamase-producing P. aeruginosa strains are not confined to a unique clonal lineage but proliferated multifocally by plasmid-mediated dissemination of the metallo-beta-lactamase gene in strains of different genetic backgrounds. Thus, further proliferation of metallo-beta-lactamase-producing strains with resistance to various beta-lactams may well be inevitable in the future, which emphasizes the need for early recognition of metallo-beta-lactamase-producing strains, rigorous infection control, and restricted clinical use of broad-spectrum beta-lactams including carbapenems.
1992年至1994年期间，从日本17家综合医院共收集了3700株铜绿假单胞菌分离株。在这些分离株中，132株对碳青霉烯耐药的菌株用金属β-内酰胺酶基因（blaIMP）特异性探针进行了DNA杂交分析。在不同地理区域的5家医院中鉴定出15株携带金属β-内酰胺酶基因的菌株。3株铜绿假单胞菌表现出对亚胺培南的高水平耐药（MIC，≥128μg/ml），2株表现出低水平亚胺培南耐药（MIC，≤4μg/ml），其余菌株的耐药水平介于两者之间。这些结果表明，仅获得金属β-内酰胺酶基因并不一定会导致对碳青霉烯类药物的耐药性升高。在几株菌株中，金属β-内酰胺酶基因由大质粒携带，并且通过电穿孔法，随着大质粒的获得，碳青霉烯耐药性从铜绿假单胞菌转移到了大肠杆菌。Southern杂交分析和基因组DNA指纹图谱显示，这15株分离株具有不同的遗传背景，尽管从同一家医院分离出的菌株有相当大的相似性。这些发现表明，产生金属β-内酰胺酶的铜绿假单胞菌菌株并不局限于单一的克隆谱系，而是通过质粒介导的金属β-内酰胺酶基因在不同遗传背景的菌株中多灶性传播而增殖。因此，未来产金属β-内酰胺酶且对各种β-内酰胺类药物耐药的菌株进一步增殖很可能是不可避免的，这强调了早期识别产金属β-内酰胺酶菌株、严格的感染控制以及限制包括碳青霉烯类药物在内的广谱β-内酰胺类药物临床使用的必要性。
