Dhandapani Sarumathi, Sistla Sujatha, Gunalan Anitha, Manoharan Meerabai, Sugumar Madhan, Sastry Apurba Sankar
Department of Microbiology, JIPMER, India.
Indian J Med Microbiol. 2021 Jan;39(1):6-10. doi: 10.1016/j.ijmmb.2020.10.018. Epub 2020 Dec 30.
The emergence of drug resistant pathogens pose major threat to hospitalized patients as well as to the community associated with increased mortality and morbidity. The treatment of carbapenem resistant enterobacteriaceae, one of the top WHO priority pathogen remains a global issue. Combination therapy with different classes of antibiotics have been tried with the aim to reduce toxicity, to increase the efficacy of the drugs and to reduce resistance. The in-vitro synergy methods have to be carried out to determine whether the combination of those antibiotics are synergistic, antagonistic or additive.
We have performed in-vitro synergy testing by checkerboard method for colistin -meropenem combination to determine whether the combination of the two antibiotics were synergistic or antagonistic.
All the consecutive twenty five blood isolates of Escherichia coli and twenty five blood isolates of Klebsiella pneumoniae which were showing resistance to carbapenems by either disc diffusion or vitek 2 were collected over a period of 6 months and checkerboard method was performed.
The reduction of MIC of colisin on combination with meropenem compared to MIC of colistin alone is analyzed by McNemar's chisquare test with the help of software Stata version 14 and p value < 0.05 is considered as significant.
56% of K. pneumoniae showed synergy and 44% showed additive/indifference results. For E. coli 40% showed synergy and 60% showed additive/indifference. None of the isolates of E. coli and K. pneumoniae showed antagonism. There was more than two fold reduction in MIC of colistin (significant) on combining withmeropenem.
The study results support the combination therapy to treat infections by multi-drug-resistant Klebsiela pneumoniae and Escherichia coli by in-vitro checkerboard testing method which inturn will be helpful for clinicians for judicious use of antimicrobials.
耐药病原体的出现对住院患者以及社区构成了重大威胁，导致死亡率和发病率上升。碳青霉烯类耐药肠杆菌科细菌是世界卫生组织重点关注的病原体之一，其治疗仍然是一个全球性问题。人们尝试了不同种类抗生素的联合治疗，目的是降低毒性、提高药物疗效并减少耐药性。必须采用体外协同试验方法来确定这些抗生素的组合是协同、拮抗还是相加作用。
我们通过棋盘法对黏菌素和美罗培南的组合进行了体外协同试验，以确定这两种抗生素的组合是协同还是拮抗作用。
在6个月的时间里，收集了所有连续的25株对碳青霉烯类耐药的大肠埃希菌血培养分离株和25株肺炎克雷伯菌血培养分离株，这些分离株通过纸片扩散法或Vitek 2检测显示对碳青霉烯类耐药，并进行了棋盘法试验。
借助Stata 14软件，通过McNemar卡方检验分析黏菌素与美罗培南联合使用时其最低抑菌浓度（MIC）相对于单独使用黏菌素时MIC的降低情况，p值<0.05被认为具有统计学意义。
56%的肺炎克雷伯菌显示出协同作用，44%显示出相加/无差异结果。对于大肠埃希菌，40%显示出协同作用，60%显示出相加/无差异。大肠埃希菌和肺炎克雷伯菌的分离株均未显示出拮抗作用。黏菌素与美罗培南联合使用时，其MIC降低了两倍以上（具有统计学意义）。
该研究结果支持通过体外棋盘试验法对多重耐药肺炎克雷伯菌和大肠埃希菌感染进行联合治疗，这反过来将有助于临床医生合理使用抗菌药物。
