与KPC-2的ω环中L169P突变相关的头孢他啶/阿维巴坦耐药性。
Ceftazidime/avibactam resistance associated with L169P mutation in the omega loop of KPC-2.
作者信息
Hemarajata Peera, Humphries Romney M
机构信息
Los Angeles Department of Public Health, Downey, CA, USA.
Accelerate Diagnostics, Tucson, AZ, USA.
出版信息
J Antimicrob Chemother. 2019 May 1;74(5):1241-1243. doi: 10.1093/jac/dkz026.
OBJECTIVES
Ceftazidime/avibactam resistance due to mutation in the omega loop of KPC-2 has been documented in vitro and in vivo. This study evaluated the mechanism of ceftazidime/avibactam resistance in a KPC-2-expressing Klebsiella pneumoniae isolated from a patient following ceftazidime/avibactam combination therapy with gentamicin for the treatment of ventilator-associated pneumonia.
METHODS
Ceftazidime/avibactam-susceptible and -resistant isolates of K. pneumoniae were evaluated by broth microdilution and WGS. The KPC-2 gene was cloned from the ceftazidime/avibactam-resistant isolate and evaluated for susceptibility to ceftazidime/avibactam, in an Escherichia coli background.
RESULTS
A single L169P mutation was identified in the KPC-2 gene between the ceftazidime/avibactam-resistant and -susceptible isolates. The novel KPC-2 allele, designated KPC-35, was shown to confer reduced susceptibility to ceftazidime/avibactam and increased susceptibility to carbapenems, as compared with KPC-2.
CONCLUSIONS
A novel L169P mutation was identified in KPC-2 and was shown through cloning experiments to confer reduced susceptibility to ceftazidime/avibactam.
目的
体外和体内研究均已证实，KPC-2的ω环突变可导致对头孢他啶/阿维巴坦耐药。本研究评估了从一名接受头孢他啶/阿维巴坦联合庆大霉素治疗呼吸机相关性肺炎的患者分离出的产KPC-2肺炎克雷伯菌对头孢他啶/阿维巴坦耐药的机制。
方法
采用肉汤微量稀释法和全基因组测序（WGS）对肺炎克雷伯菌对头孢他啶/阿维巴坦敏感和耐药的分离株进行评估。从对头孢他啶/阿维巴坦耐药的分离株中克隆KPC-2基因，并在大肠杆菌背景下评估其对头孢他啶/阿维巴坦的敏感性。
结果
在对头孢他啶/阿维巴坦耐药和敏感的分离株之间，KPC-2基因中鉴定出一个单一的L169P突变。与KPC-2相比，新的KPC-2等位基因，命名为KPC-35，显示出对头孢他啶/阿维巴坦的敏感性降低，对碳青霉烯类的敏感性增加。
结论
在KPC-2中鉴定出一种新的L169P突变，通过克隆实验表明该突变可导致对头孢他啶/阿维巴坦的敏感性降低。
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