Testing the in vitro efficacy of colistin and meropenem combination with flow cytometry method in colistin and carbapenem resistant acinetobacter baumannii and klebsiella pneumoniae strains and comparison with checkerboard method

Nowadays, colistin has been used more frequently in treatments with the increase in carbapenem resistance in gram-negative bacteria. As a consequence, resistance to colistin is gradually increasing. It was aimed to investigate the in vitro efficacy of colistin and meropenem combination with both flow cytometry-based time-kill and checkerboard synergy test methods in colistin and carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae strains in this study. It was studied with both flow cytometry-based time-kill and checkerboard synergy test methods after colistin resistance was confirmed by broth microdilution method in ten different A. baumannii and ten different K. pneumoniae strains resistant to colistin and carbapenem. In addition, the strains also studied with the gradient diffusion synergy test method. The results were evaluated by calculating the fractional inhibitor concentration for the checkerboard and gradient diffusion synergy test method and the increase-decrease at the logarithm base for the time kill. It was found that the synergistic, additive, and indifference efficacy for Klebsiella pneumoniae strains were 40%, 50%, and 10%, and also for A. baumannii strains were 70%, 20%, and 10% respectively considering the checkerboard method. However, indifference activity was observed in all strains in the time-kill method. 55% agreement was found between flow cytometry-based time kill and gradient diffusion while it was meeting 10% of correlation between flow cytometry-based time-kill and checkerboard synergy test methods. We could not find any study about the interaction of antibiotic combinations using a flow cytometry-based synergy test on patient isolates in the literature. This study is remarkable considering modernizing the traditional method and taking quick results. However, the correlation between the tests should be improved because of the inconsistency between the tests inherent in synergy tests.