BACKGROUND Treatment of pandrug-resistant isolates often necessitates combination therapy. Checkerboard synergy and time-killing assay tests were performed to evaluate the benefits of a triple combination with meropenem, ertapenem, and colistin against 10 colistin-resistant K. pneumoniae clinical isolates harboring different β-lactamases. (blaOXA-48, blaNDM). MATERIALS AND METHODS In this study, ertapenem and meropenem (ERT/MEM), meropenem and colistin (MEM/COL), ertapenem, meropenem and colistin (ERT/MEM/COL) combinations were tested using checkerboard techniques and time-kill assays of each antibiotic alone and in combination against 10 colistin-resistant clinical K. pneumoniae isolates. An analysis of K. pneumoniae isolate B6 using a scanning electron microscope revealed morphologic changes in the cell surface after treatment with each antibiotic both alone and in combination. The whole genome of K. pneumoniae KPNB1 was sequenced using an Ion Torrent PGM sequencer. RESULTS According to the checkboard results, synergistic combinations were observed with ertapenem/meropenem (5/10 isolates), meropenem/colistin (7/10) and ertapenem/meropenem/colistin (9/10); no antagonism was observed for all combinations. For the time-kill assay results; synergism and bactericidal effects were observed with meropenem/colistin (10/10) and with ertapenem/meropenem/colistin (10/10) combinations, and an indifference effect was observed with the ertapenem and meropenem (10/10) combination. Strain number 1 was found 100% identical to Klebsiella pneumoniae subsp. pneumoniae HS11286 according to the outcomes of complete genome sequence analysis, and the strain carried the genes blaOXA-181, blaCTXM-15, blaNDM, arr-3, aac (6')-Ib-cr, rmtF, and catB1. CONCLUSION Using double carbapenem antibiotics with colistin could be a potential alternative to treat colistin and carbapenem-resistant K. pneumoniae. The present study is the first Turkish report of OXA-181-type carbapenemase causing colistin resistance.

中文翻译：

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在体外评估双碳青霉烯和大肠菌素组合抗OXA-48，NDM碳青霉烯酶生产的大肠菌素耐药性肺炎克雷伯菌。

背景技术对耐泛药的分离株的治疗通常需要联合治疗。进行了棋盘协同和杀伤时间测定试验，以评估美罗培南，厄他培南和粘菌素三联组合对10种带有不同β-内酰胺酶的粘菌抗性肺炎克雷伯菌临床分离株的益处。（blaOXA-48，blaNDM）。材料与方法在这项研究中，使用了棋盘技术和每种产品的时间杀灭试验，对厄他培南和美洛培南（ERT / MEM），美洛培南和大肠粘菌素（MEM / COL），厄他培南，美洛培南和大肠粘菌素（ERT / MEM / COL）组合进行了测试。单独和联合使用抗生素可抵抗10种对大肠菌素耐药的临床肺炎克雷伯菌分离株。对K的分析。使用扫描电子显微镜观察到的肺炎分离株B6单独或联合使用每种抗生素后，细胞表面形态发生了变化。肺炎克雷伯氏菌KPNB1的整个基因组使用Ion Torrent PGM测序仪测序。结果根据检查结果，与厄他培南/美罗培南（5/10个分离株），美罗培南/ colistin（7/10）和厄他培南/美罗培南/ colistin（9/10）有协同作用。没有观察到所有组合的拮抗作用。对于时间杀伤分析结果；美洛培南/ colistin（10/10）和厄他培南/美洛培南/ colistin（10/10）组合观察到协同作用和杀菌作用，而美洛培南和美洛培南（10/10）组合观察到无差异作用。发现菌株1与肺炎克雷伯菌亚种100％相同。根据完整基因组序列分析的结果，该菌株携带了blaOXA-181，blaCTXM-15，blaNDM，arr-3，aac（6'）-Ib-cr，rmtF和catB1基因。结论将双碳青霉烯类抗生素与粘菌素一起使用可能是治疗大肠粘菌素和碳青霉烯耐药性肺炎克雷伯菌的潜在替代方法。本研究是土耳其第一份引起大肠菌素抗性的OXA-181型碳青霉烯酶的报道。