Epidemiology and carbapenem resistance mechanisms of carbapenem-non-susceptible Pseudomonas aeruginosa collected during 2009-11 in 14 European and Mediterranean countries
Epidemiology and carbapenem resistance mechanisms of carbapenem-non-susceptible Pseudomonas aeruginosa collected during 2009-11 in 14 European and Mediterranean countries
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DOI：
10.1093/jac/dku048
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发表时间：
2014-07-01
影响因子：
5.2
通讯作者：
Jones, Ronald N.
中科院分区：
文献类型：
--
作者：
Castanheira, Mariana;Deshpande, Lalitagauri M.;Jones, Ronald N.
目的评价2009- 2011年在欧洲和地中海14个国家收集的碳青霉烯非敏感铜绿假单胞菌的遗传亲缘关系及耐药机制。检测多利培南非敏感（MIC > 2 mg/L）分离株对亚胺培南、美罗培南、多利培南、唑曲南、头孢他啶和头孢吡肟的敏感性，同时检测是否含苯基精氨酸- β -萘酰胺（PA β N）（外排抑制剂）和/或氯西林（AmpC抑制剂）。碳青霉烯酶筛选通过PCR和测序。以铜绿假单胞菌（P. aeruginosa PAO1）或一组敏感菌株为基线，采用实时荧光定量PCR检测染色体ampC、mexA、mexC、mexE和mexX的表达。通过PFGE和多位点序列分型评估克隆性。529株（25.6%）对碳青霉烯不敏感的铜绿假单胞菌（P. aeruginosa）中，金属β -内酰胺酶（M β L）编码VIM-2（76株）、VIM-4（14株）、VIM-1（7株）和VIM-5（5株）基因阳性106株。在1株菌株中检测到IMP-15和3个新的M β l （IMP-33、VIM-36和VIM-37）。与前几年（2009年和2010年分别为13.4%和12.3%）相比，2011年M β L生产者的患病率有所上升（30.6%）。分离株具有较高的遗传多样性，共检测到401个独特的基因图谱。在产生M β l的群体中检测到CC235和ST111。PA β N/cloxacillin效应范围为90.0% ~ 56.5%/ 1.3% ~ 21.2%。OprD减少/丢失是最普遍的内在机制，在94.9%的铜绿假单胞菌中检测到，其次是AmpC（44.4%）和MexAB-OprM（20.1%）。当使用敏感组分离株作为基线时，MexAB-OprM与OprD减少/丢失一样普遍。在欧洲各国，不断增加的β L患病率令人担忧；然而，高度遗传多样性的碳青霉烯不敏感铜绿假单胞菌群体的内在耐药机制可能是这些国家更值得关注的问题。
To evaluate the genetic relatedness and carbapenem resistance mechanisms among carbapenem-non-susceptible Pseudomonas aeruginosa collected during 2009-11 in 14 European and Mediterranean countries.Doripenem-non-susceptible (MIC > 2 mg/L) isolates were tested for susceptibility to imipenem, meropenem, doripenem, aztreonam, ceftazidime and cefepime with and without phenyl-arginine-beta-naphthylamide (PA beta N) (efflux inhibitor) and/or cloxacillin (AmpC inhibitor). Carbapenemase screening was performed by PCR and sequencing. Expression of chromosomal ampC, mexA, mexC, mexE and mexX was determined by quantitative real-time PCR using P. aeruginosa PAO1 or a group of susceptible isolates as baseline. Clonality was evaluated by PFGE and multilocus sequence typing.Among 529 (25.6% overall) carbapenem-non-susceptible P. aeruginosa, 106 were positive for metallo-beta-lactamase (M beta L) genes encoding VIM-2 (76 strains), VIM-4 (14), VIM-1 (7) and VIM-5 (5). IMP-15 and three new M beta Ls (IMP-33, VIM-36 and VIM-37) were detected in one strain each. An increasing prevalence of M beta L producers was noted in 2011 (30.6%) compared with previous years (13.4% and 12.3% in 2009 and 2010, respectively). Isolates displayed high genetic diversity, with 401 unique profiles detected. CC235 and ST111 were detected among M beta L-producing clusters. The PA beta N/cloxacillin effect ranged from 90.0% to 56.5%/from 1.3% to 21.2%. OprD decrease/loss was the most prevalent intrinsic mechanism and was detected among 94.9% of the P. aeruginosa, followed by AmpC (44.4%) and MexAB-OprM (20.1%). When using the susceptible group of isolates as baseline, MexAB-OprM became as prevalent as OprD decrease/loss.Increasing M beta L prevalence is worrisome in various European countries; however, intrinsic resistance mechanisms in a highly genetically diverse population of carbapenem-non-susceptible P. aeruginosa are probably a matter for greater concern in these countries.