Investigation of the effect of efflux PUMP inhibitors on the efficacy of various antibiotics in bacteria isolated from clinical specimens

Antibiotic resistance, one of the most important public health problems faced by humanity, requires new strategies and approaches to develop new antimicrobial agents. Although developments regarding efflux pump inhibitors (DAPI) and other candidate agents are promising, the search for increasing the duration and effectiveness of existing antibiotics continues. In this study, the antibacterial effect of three DAPIs, verapamil (VER), reserpine (REZ) and carbonyl cyanide 3-chlorophenylhydrazone (CCCP), against 5 standard strains and 15 clinical isolates were determined by disc diffusion and broth microdilution method, and the synergistic interactions with various antibiotics by the checkerboard method. Within the scope of the study, 3 clinical isolates of Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli and Enterococcus faecalis each and Staphylococcus aureus, K. pneumoniae ATCC 700603, P. aeruginosa ATCC 27853, E. coli ATCC 25922, S. aureus ATCC 29213 and E. faecalis ATCC 29212 standard strains were used. Although the antibacterial effect of the efflux pump inhibitors alone were not strong, the interaction with the antibiotics tested was mostly synergistic or additive. In this study, the demonstration that efflux pump inhibitors can decrease the minimum inhibitory concentration values of the tested antibiotics, as a result of their possible interaction with the efflux pumps in the isolates used, supports the throughts that the combined use of efflux pump inhibitors with antibiotics may increase the effect spectrum of antibiotics, reduce the level of resistance to antibiotics and the frequency of occurrence of resistance in bacteria.