Aix Marseille Univ, IRD, APHM, MEPHI, IHU Méditerranée Infection, 19-21 Boulevard Jean Moulin, 13385 Marseille CEDEX 05, France.
Department of Medical Biopathology and Clinical Microbiology, Aeginition Hospital, Athens Medical School, National and Kapodistrian University of Athens, Ave Vassilissis Sophias 72, 11528 Athens, Greece.
Int J Antimicrob Agents. 2020 Apr;55(4):105930. doi: 10.1016/j.ijantimicag.2020.105930. Epub 2020 Mar 1.
In Greece, the spread of carbapenem-resistant Enterobacteriaceae in humans has led to the reintroduction of colistin as a therapeutic agent. Unfortunately, colistin resistance with different mechanisms has emerged. The present work aims to determine the prevalence of carbapenem and colistin resistance and the corresponding mechanisms in Klebsiella pneumoniae clinical isolates from Greece.
From 2014 to 2017, 288 carbapenem-resistant K. pneumoniae clinical strains were gathered from a collection of 973 isolates from eight different hospitals in Greece. Antibiotic susceptibility testing was performed using three different methods. Screening of carbapenem and colistin resistance genes was conducted using polymerase chain reaction (PCR) amplification and sequencing.
Among the 288 (29.6 %) carbapenem-resistant isolates, 213 (73.9%) were colistin-resistant (minimum inhibitory concentration [MIC] >2 mg/L). The KPC type was the most common carbapenemase gene (116; 40.3%), followed by VIM (41; 14.2%), NDM (33; 11.5%) and OXA-48 (22; 7.6%). Moreover, 44 (15.3%) strains co-produced two types of carbapenemases. No mcr genes were detected for colistin resistance but mutations in chromosomal genes were found. These included inactivation of the mgrB gene for 148 (69.5%) strains, including insertion sequences for 94 (44.1%), nonsense mutations for 4 (1.9%) and missense mutations for 24 (11.3%). Moreover, PCR amplification of mgrB gene was negative for 26 (12.2%) strains. Finally, 65 (30.5%) colistin-resistant strains exhibited a wild-type mgrB, the mechanisms of which remain to be elucidated.
This study shows that K. pneumoniae clinical strains in Greece are resistant to both carbapenems and colistin and this is endemic and is likely chromosomally encoded.
在希腊，碳青霉烯类耐药肠杆菌科细菌在人类中的传播导致多粘菌素重新被用作治疗药物。不幸的是，不同机制的多粘菌素耐药性已经出现。本研究旨在确定希腊分离的肺炎克雷伯菌临床株中碳青霉烯类和多粘菌素类耐药的流行情况以及相应的机制。
2014 年至 2017 年，从希腊 8 家不同医院的 973 株分离株中收集了 288 株碳青霉烯类耐药肺炎克雷伯菌临床株。采用三种不同方法进行抗生素敏感性试验。采用聚合酶链反应（PCR）扩增和测序法筛选碳青霉烯类和多粘菌素类耐药基因。
在 288 株（29.6%）碳青霉烯类耐药分离株中，213 株（73.9%）对多粘菌素耐药（最小抑菌浓度[MIC]＞2 mg/L）。最常见的碳青霉烯酶基因是 KPC 型（116 株；40.3%），其次是 VIM 型（41 株；14.2%）、NDM 型（33 株；11.5%）和 OXA-48 型（22 株；7.6%）。此外，44 株（15.3%）菌株同时产生两种类型的碳青霉烯酶。未发现 mcr 基因导致多粘菌素耐药，但发现了染色体基因的突变。这些突变包括 148 株（69.5%）mgrB 基因失活，其中 94 株（44.1%）存在插入序列，4 株（1.9%）存在无义突变，24 株（11.3%）存在错义突变。此外，26 株（12.2%）菌株 mgrB 基因的 PCR 扩增呈阴性。最后，65 株（30.5%）多粘菌素耐药株表现出野生型 mgrB，但耐药机制仍有待阐明。
本研究表明，希腊分离的肺炎克雷伯菌临床株对碳青霉烯类和多粘菌素类均有耐药性，且这种耐药性是地方性的，可能与染色体编码有关。
