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作为MagicBullet临床试验的一部分,在希腊、意大利和西班牙,从呼吸机相关性肺炎患者中分离出的多重耐药和广泛耐药铜绿假单胞菌菌株的高发生率。

High incidence of MDR and XDR Pseudomonas aeruginosa isolates obtained from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the MagicBullet clinical trial.

作者信息

Pérez Astrid, Gato Eva, Pérez-Llarena José, Fernández-Cuenca Felipe, Gude María José, Oviaño Marina, Pachón María Eugenia, Garnacho José, González Verónica, Pascual Álvaro, Cisneros José Miguel, Bou Germán

机构信息

Microbiology Department, Biomedical Research Institute A Coruña (INIBIC), University Hospital A Coruña (CHUAC), University of A Coruña (UDC), A Coruña, Spain.

Unidad de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena, Seville, Spain.

出版信息

J Antimicrob Chemother. 2019 May 1;74(5):1244-1252. doi: 10.1093/jac/dkz030.

Abstract

OBJECTIVES

To characterize the antimicrobial susceptibility, molecular epidemiology and carbapenem resistance mechanisms in Pseudomonas aeruginosa isolates recovered from respiratory tract samples from patients with ventilator-associated pneumonia enrolled in the MagicBullet clinical trial.

METHODS

Isolates were collected from 53 patients from 12 hospitals in Spain, Italy and Greece. Susceptibility was determined using broth microdilution and Etest. MALDI-TOF MS was used to detect carbapenemase activity and carbapenemases were identified by PCR and sequencing. Molecular epidemiology was investigated using PFGE and MLST.

RESULTS

Of the 53 isolates, 2 (3.8%) were considered pandrug resistant (PDR), 19 (35.8%) were XDR and 16 (30.2%) were MDR. Most (88.9%) of the isolates from Greece were MDR, XDR or PDR, whereas fewer of the isolates from Spain (33.3%) and Italy (43.5%) showed antibiotic resistance. Three Greek isolates were resistant to colistin. Overall, the rates of resistance of P. aeruginosa isolates to imipenem, ciprofloxacin, ceftolozane/tazobactam and ceftazidime/avibactam were 64.1%, 54.7%, 22.6% and 24.5%, respectively. All isolates resistant to ceftolozane/tazobactam and ceftazidime/avibactam (Greece, n = 10; and Italy, n = 2) carried blaVIM-2. Spanish isolates were susceptible to the new drug combinations. Forty-eight restriction patterns and 27 STs were documented. Sixty percent of isolates belonged to six STs, including the high-risk clones ST-111, ST-175 and ST-235.

CONCLUSIONS

MDR/XDR isolates were highly prevalent, particularly in Greece. The most effective antibiotic against P. aeruginosa was colistin, followed by ceftolozane/tazobactam and ceftazidime/avibactam. blaVIM-2 is associated with resistance to ceftolozane/tazobactam and ceftazidime/avibactam, and related to highly resistant phenotypes. ST-111 was the most frequent and disseminated clone and the clonal diversity was lower in XDR and PDR strains.

摘要

目的

对从参与MagicBullet临床试验的呼吸机相关性肺炎患者呼吸道样本中分离出的铜绿假单胞菌菌株的抗菌药物敏感性、分子流行病学及碳青霉烯类耐药机制进行特征分析。

方法

从西班牙、意大利和希腊12家医院的53例患者中收集菌株。采用肉汤微量稀释法和Etest法测定敏感性。使用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF MS)检测碳青霉烯酶活性,并通过聚合酶链反应(PCR)和测序鉴定碳青霉烯酶。采用脉冲场凝胶电泳(PFGE)和多位点序列分型(MLST)研究分子流行病学。

结果

53株菌株中,2株(3.8%)被认为对所有药物耐药(PDR),19株(35.8%)为广泛耐药(XDR),16株(30.2%)为多重耐药(MDR)。希腊分离出的菌株中大多数(88.9%)为MDR、XDR或PDR,而西班牙(33.3%)和意大利(43.5%)分离出的菌株中显示抗生素耐药的较少。3株希腊分离株对黏菌素耐药。总体而言,铜绿假单胞菌菌株对亚胺培南、环丙沙星、头孢洛扎/他唑巴坦和头孢他啶/阿维巴坦的耐药率分别为64.1%、54.7%、22.6%和24.5%。所有对头孢洛扎/他唑巴坦和头孢他啶/阿维巴坦耐药的菌株(希腊,n = 10;意大利,n = 2)均携带blaVIM-2。西班牙分离株对新的药物组合敏感。记录了48种限制性酶切图谱和27种序列型。60%的菌株属于6种序列型,包括高危克隆ST-111、ST-175和ST-235。

结论

MDR/XDR菌株高度流行,尤其是在希腊。针对铜绿假单胞菌最有效的抗生素是黏菌素,其次是头孢洛扎/他唑巴坦和头孢他啶/阿维巴坦。blaVIM-2与对头孢洛扎/他唑巴坦和头孢他啶/阿维巴坦的耐药相关,并与高度耐药表型有关。ST-111是最常见且传播最广的克隆,XDR和PDR菌株的克隆多样性较低。

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