In-vitro synergistic activity of colistin and meropenem against clinical isolates of carbapenem resistant E.coli and Klebsiella pneumoniae by checkerboard method

Context: 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 entero-bacteriaceae, 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. Aims: 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. Methods and material: 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. Statistical analysis used: 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. Results: 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. Conclusions: 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.

Automated summary

The study conducted in-vitro synergy testing using the checkerboard method on colistin-meropenem combination to determine whether the antibiotics had synergistic or antagonistic effects. The results showed that a significant reduction in MIC of colistin was observed when combined with meropenem, supporting the use of combination therapy for infections caused by multi-drug-resistant Klebsiella pneumoniae and Escherichia coli.