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首页> 外文期刊>The Journal of Antimicrobial Chemotherapy >Pseudomonas aeruginosa carbapenem resistance mechanisms in Spain: impact on the activity of imipenem, meropenem and doripenem.
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Pseudomonas aeruginosa carbapenem resistance mechanisms in Spain: impact on the activity of imipenem, meropenem and doripenem.

机译：西班牙的铜绿假单胞菌碳青霉烯耐药机制：对亚胺培南，美罗培南和多立培南活性的影响。

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OBJECTIVES: To investigate the mechanisms of carbapenem resistance in the 175 Pseudomonas aeruginosa isolates (39%; 175/448) showing non-susceptibility (European Committee on Antimicrobial Susceptibility Testing breakpoints) to imipenem (35%), meropenem (33%) and/or doripenem (33%) recovered in 2008-09 from 16 Spanish hospitals during the Comparative Activity of Carbapenem Testing (COMPACT) surveillance study. METHODS: MICs (Etest), clonal relatedness (PFGE) and metallo-beta-lactamase (MBL) production (Etest-MBL, PCR and sequencing) were determined. Mutation-driven resistance was studied in 60 non-MBL producers according to the doripenem MICs (15 isolates from each of four MIC groups: /= 32 mg/L). The expression of ampC, mexB, mexY, mexD and mexF was determined by real-time reverse transcription-PCR and the presence of mutations in oprD by PCR and sequencing. Isogenic mutants expressing combinations of mutation-driven carbapenem resistance were constructed. RESULTS: Twelve (6.9%) isolates were MBL (VIM-20, VIM-2 or VIM-13) producers and all showed high-level resistance (MIC 32 mg/L) to all three carbapenems. Regarding mutation-driven resistance, all but 1 of the 60 isolates were non-susceptible (MIC >32 mg/L) to imipenem, linked to oprD inactivation. In addition, 50% of the isolates overexpressed ampC, 33% mexY, 32% mexB and 15% mexF, while none overexpressed mexD. Increasing prevalence of ampC overexpression correlated with increasing doripenem MICs (/= 32, 73%) while overexpression of efflux pumps correlated only with moderate resistance. Doripenem showed slightly higher activity than meropenem against isolates overexpressing ampC, especially mexB or mexY. The analysis of a collection of isogenic laboratory mutants supported this finding. CONCLUSIONS: Although the prevalence of MBL producers is increasing, mutation-driven resistance is still more frequent in Spain. Imipenem resistance was driven by OprD inactivation, while additional AmpC and particularly efflux pump hyperproduction had a lower impact on the activity of doripenem compared with meropenem.
机译：目的：研究175株铜绿假单胞菌（39％; 175/448）对碳青霉烯耐药性的机制，这些分离株对亚胺培南（35％），美罗培南（33％）和//对亚胺培南（欧洲抗菌药物敏感性试验断点）无敏感性或2008年9月，在碳青霉烯测试比较活动（COMPACT）监测研究中从16家西班牙医院中回收的多立培南（33％）。方法：测定MIC（Etest），克隆相关性（PFGE）和金属β-内酰胺酶（MBL）产生（Etest-MBL，PCR和测序）。在60个非MBL生产者中，根据多瑞培南MICs（来自四个MIC组的15种分离株： / = 32 mg / L）研究了突变驱动的抗性。通过实时逆转录PCR确定ampC，mexB，mexY，mexD和mexF的表达，并通过PCR和测序确定oprD中突变的存在。构建表达突变驱动的碳青霉烯抗性组合的同基因突变体。结果：MBL（VIM-20，VIM-2或VIM-13）的生产者中有十二个（6.9％）分离株对所有三个碳青霉烯均表现出高水平抗药性（MIC 32 mg / L）。关于突变驱动的抗药性，在60株分离株中，除1株对亚胺培南不敏感（MIC> 32 mg / L），与oprD失活有关。此外，有50％的分离株过表达ampC，33％的mexY，32％的mexB和15％的mexF，而没有一个过表达mexD。 ampC过表达的患病率增加与多瑞培南MIC的增加有关（ / = 32，73％），而外排泵的过表达仅与中等抵抗力。多瑞培南对过表达ampC的分离株，特别是mexB或mexY，显示出比美罗培南稍高的活性。对等基因实验室突变体集合的分析支持了这一发现。结论：尽管MBL生产者的流行正在增加，但在西班牙突变驱动的抗性仍然更加频繁。亚胺培南耐药性是由OprD失活驱动的，与美罗培南相比，额外的AmpC尤其是外排泵超量生产对多利培南的活性影响较小。

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