Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.
Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.
J Glob Antimicrob Resist. 2022 Sep;30:357-362. doi: 10.1016/j.jgar.2022.07.002. Epub 2022 Jul 8.
Infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) pose a huge health challenge worldwide. The aim of this study was to evaluate the incidence of polymyxin resistance in clinical CRKP isolates in China and to characterize the molecular mechanisms underlying these polymyxin-resistant CRKP (PR-CRKP) isolates.
A total of 493 CRKP clinical isolates from patients were collected from six tertiary-care hospitals in China during 2017-2018. Minimum inhibitory concentrations of polymyxin B and colistin were determined using the broth microdilution method. PR-CRKP isolates were identified and subjected to whole-genome sequencing. Quantitative real-time PCR and structural modelling analysis were also performed.
We observed a 2.2% (11/493) polymyxin resistance rate in this multicentre cohort. Polymyxin B MICs ranged from 4 to 64 μg/mL and colistin MICs ranged from 8 to 128 μg/mL in 11 PR-CRKP isolates. Key genetic variations identified in PR-CRKP isolates involved eight disruptions (seven insertional inactivation by an insertion sequence [IS] element, one frameshift deletion) in mgrB, and three missense mutations in pmrA, pmrB, and phoP. ISKpn26 was the predominant IS (4/7), and three of these occurred in nucleotide position 74 in the mgrB gene. In addition, we reported a novel mutation S62R in pmrB that may confer polymyxin resistance in K. pneumoniae.
Our findings highlight the multifaceted molecular mechanisms of polymyxin resistance in CRKP.
耐碳青霉烯类肺炎克雷伯菌（CRKP）引起的感染在全球范围内构成了巨大的健康挑战。本研究旨在评估中国临床 CRKP 分离株中多粘菌素耐药的发生率，并对这些多粘菌素耐药 CRKP（PR-CRKP）分离株的分子机制进行特征描述。
本研究共收集了来自中国六家三级医院的 493 例 CRKP 临床分离株，这些分离株均来自于 2017-2018 年的患者。采用肉汤微量稀释法测定多粘菌素 B 和粘菌素的最小抑菌浓度。鉴定多粘菌素耐药 CRKP 分离株并进行全基因组测序。还进行了定量实时 PCR 和结构建模分析。
在这项多中心队列研究中，我们观察到 2.2%（11/493）的多粘菌素耐药率。11 株 PR-CRKP 分离株的多粘菌素 B MIC 值范围为 4-64μg/ml，粘菌素 MIC 值范围为 8-128μg/ml。PR-CRKP 分离株中发现的关键遗传变异涉及 mgrB 中的 8 个中断（7 个由插入序列[IS]元件引起的插入失活，1 个框移缺失），以及 pmrA、pmrB 和 phoP 中的 3 个错义突变。ISKpn26 是主要的 IS（4/7），其中 3 个位于 mgrB 基因的 74 号核苷酸位置。此外，我们还报道了 K. pneumoniae 中 pmrB 基因的新突变 S62R，该突变可能导致多粘菌素耐药。
我们的研究结果强调了 CRKP 中多粘菌素耐药的多方面分子机制。
