Diclofenac increases the susceptibility of Pseudomonasaeruginosa to gentamicin through the inhibition of bacterial effluxpumps

Background and Aim : Pseudomonas aeruginosa is an opportunistic human pathogen exhibitinginnate resistance to multiple antimicrobial agents. This intrinsic multidrug resistance is caused bysynergy between a low-permeable outer membrane and a number of multidrug efflux systems.Non-steroid anti-inflammatory drugs have shown the antimicrobial potential to be used incombination with antibiotics against bacterial pathogens. Diclofenac is a non-steroidal antiinflammatorydrug (NSAID) which has been shown to increase the susceptibility of variousbacteria to antimicrobials and demonstrated to have broad antimicrobial activity. Therefore, thecurrent work was conducted to evaluate the synergistic effect of diclofenac with gentamicin andits effect on inhibition of efflux pumps activity in clinical P. aeruginosa strains.Methods : Gentamicin resistance was determined using disk diffusion method and the synergismof diclofenac and gentamicin was investigated using the checkerboard titration assay. Finally, theefflux pump activity was determined by ethidium bromide (EtBr) cartwheel method.Results : The average inhibition zone around gentamicin disks impregnated with diclofenac were۲۳ and ۲۴ mm for pathogenic and ATCC strains, respectively, which were significantly greaterthan the inhibition zones around the antibiotic alone. The checkerboard titration assay revealedsynergism of the drugs with fractional inhibitory concentration (FIC) of ۰.۵. At the end, the cartwheel method showed that diclofenac in combination with gentamicin was able to reduce theextrusion of ethidium bromide from bacterial cytoplasm.Conclusion : This study showed that simultaneous treatment with diclofenac and gentamicin cantarget efflux pumps activity of P. aeruginosa that could be a promising approach against drugresistantP. aeruginosa infections, after further characterization.

کلیدواژه ها:

Diclofenac ، Efflux pump ، Pseudomonas aeruginosa ، Gentamicin