Centre National de Référence de la Résistance aux Antibiotiques, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France.
J Antimicrob Chemother. 2013 Aug;68(8):1772-80. doi: 10.1093/jac/dkt098. Epub 2013 Apr 14.
Pseudomonas aeruginosa can become resistant to carbapenems by both intrinsic (mutation-driven) and transferable (β-lactamase-based) mechanisms. Knowledge of the prevalence of these various mechanisms is important in intensive care units (ICUs) in order to define optimal prevention and therapeutic strategies.
A total of 109 imipenem-non-susceptible (MIC >4 mg/L) strains of P. aeruginosa were collected in June 2010 from the ICUs of 26 French public hospitals. Their resistance mechanisms were characterized by phenotypic, enzymatic, western blotting and molecular methods.
Single or associated imipenem resistance mechanisms were identified among the 109 strains. Seven isolates (6.4%) were found to produce a metallo-β-lactamase (one VIM-1, four VIM-2, one VIM-4 and one IMP-29). Porin OprD was lost in 94 (86.2%) strains as a result of mutations or gene disruption by various insertion sequences (ISPa1635, ISPa1328, IS911, ISPs1, IS51, IS222 and ISPa41). Thirteen other strains were shown to be regulatory mutants in which down-regulation of oprD was coupled with overexpressed efflux pumps CzcCBA (n = 1), MexXY (n = 9) and MexEF-OprN (n = 3). The lack of OprD was due to disruption of the oprD promoter by ISPsy2 in one strain and alteration of the porin signal sequence in another.
Imipenem resistance in ICU P. aeruginosa strains may result from multiple mechanisms involving metallo-β-lactamase gene acquisition and genetic events (mutations and ISs) inactivating oprD, turning down its expression while increasing efflux activities or preventing insertion of porin OprD in the outer membrane. This diversity of mechanisms allows P. aeruginosa, more than any other nosocomial pathogen, to rapidly adapt to carbapenems in ICUs.
铜绿假单胞菌可以通过内在（由突变驱动）和可转移（基于β-内酰胺酶）机制对碳青霉烯类药物产生耐药性。了解这些不同机制的流行情况对于重症监护病房（ICU）非常重要，以便确定最佳的预防和治疗策略。
2010 年 6 月，从法国 26 家公立医院的 ICU 中收集了 109 株对亚胺培南不敏感（MIC>4mg/L）的铜绿假单胞菌。通过表型、酶学、western blot 和分子方法对其耐药机制进行了表征。
在 109 株菌中发现了一种或多种亚胺培南耐药机制。7 株（6.4%）分离株产生金属β-内酰胺酶（1 株 VIM-1、4 株 VIM-2、1 株 VIM-4 和 1 株 IMP-29）。由于各种插入序列（ISPa1635、ISPa1328、IS911、ISPs1、IS51、IS222 和 ISPa41）引起的突变或基因缺失，94 株（86.2%）菌株失去了孔蛋白 OprD。另外 13 株菌被证明是调节突变体，其中 oprD 的下调与过度表达的外排泵 CzcCBA（n=1）、MexXY（n=9）和 MexEF-OprN（n=3）相关。一株菌中 oprD 启动子被 ISPsy2 破坏，另一株菌中孔蛋白信号序列发生改变，导致 oprD 缺失。
ICU 铜绿假单胞菌菌株对亚胺培南的耐药性可能由多种机制引起，包括获得金属β-内酰胺酶基因以及失活 oprD 的遗传事件（突变和 ISs），从而降低其表达水平，同时增加外排活性或阻止外膜中孔蛋白 OprD 的插入。这种机制的多样性使铜绿假单胞菌比任何其他医院病原体都能更快地适应 ICU 中的碳青霉烯类药物。
