Bedenić Branka, Car Haris, Slačanac Domagoj, Sviben Mario, Čačić Marko, Lukić-Grlić Amarela, Benčić Ana, Šijak Dorotea, Tripković Marko, Beader Nataša
School of Medicine, University of Zagreb, Zagreb, Croatia; Department of Clinical and Molecular Microbiology, University Hospital Center Zagreb, Zagreb, Croatia.
Secondary Medical School, Zagreb, Croatia.
J Infect Chemother. 2018 Dec;24(12):1016-1019. doi: 10.1016/j.jiac.2018.06.001. Epub 2018 Jul 11.
The aim of the study was to determine in vitro synergy and postantibiotic effect of colistin alone and combined with meropenem or vancomycin against Enterobacteriaceae producing multiple carbapenemases; combinations of two metallo-β-lactamases (MBL) or MBL with OXA-48. Colistin-resistant strain positive for OXA-48 was also included in the study.
The antibiotic susceptibility was tested by broth microdilution method. Synergy was tested by chequerboard, time-kill and 2-well method. PAE was determined by viable counting.
The chequerboard analysis revealed synergy for colistin combination with meropenem in all isolates with FICI values ranging from 0.12 to 0.24. FICI values for combinations with vancomycin were below 0.5 indicating synergy in two out of four isolates. K. pneumoniae 609815 positive for OXA-48 and colistin resistant showed the most pronounced and consistent synergy effect with meropenem in both chequerboard and time-kill method. Synergy effect in time-kill curves, was observed for K pneumoniae 145846 with two MBLs and colistin resistant K. pneumoniae 609815 positive for OXA-48, with both combinations including meropenem and vancomycin. Colistin alone exhibited short postantibiotic effect (PAE) against all tested isolates. Meropenem markedly prolonged the PAE in two isolates in contrast to vancomycin which did not demonstrate significant effect on the duration of PAE.
The synergy effect and the duration of PAE was strain and antibiotic dependent but not related to the resistance gene content.
本研究旨在确定单独使用黏菌素以及黏菌素与美罗培南或万古霉素联合使用对产多种碳青霉烯酶的肠杆菌科细菌的体外协同作用和抗生素后效应；两种金属β-内酰胺酶（MBL）或MBL与OXA-48的组合。对OXA-48呈阳性的耐黏菌素菌株也纳入了研究。
采用肉汤微量稀释法检测抗生素敏感性。通过棋盘法、时间杀菌法和双孔法检测协同作用。通过活菌计数法测定抗生素后效应。
棋盘分析显示，黏菌素与美罗培南联合使用对所有分离株均有协同作用，FICI值范围为0.12至0.24。与万古霉素联合使用的FICI值低于0.5，表明在四分之二的分离株中有协同作用。对OXA-48呈阳性且耐黏菌素的肺炎克雷伯菌609815在棋盘法和时间杀菌法中与美罗培南均表现出最显著和一致的协同效应。在时间杀菌曲线中，观察到携带两种MBL的肺炎克雷伯菌145846以及对OXA-48呈阳性的耐黏菌素肺炎克雷伯菌609815在美罗培南和万古霉素两种组合中均有协同效应。单独使用黏菌素对所有测试分离株的抗生素后效应（PAE）较短。与万古霉素相比，美罗培南显著延长了两株分离株的PAE，而万古霉素对PAE持续时间未显示出显著影响。
协同效应和PAE持续时间因菌株和抗生素而异，但与耐药基因含量无关。
