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Background: The high-level antimicrobial resistance particularly carbapenem resistance in Pseudomonas aeruginosa is a global health challenge. The combination of antibiotics and synergy effects is beneficial in control of drug-resistant P. aeruginosa. The synergic interaction of antimicrobial agents is affected by the mechanisms of antimicrobial resistance. The aim of current study was to evaluate the effect of efflux pumps inhibition on the synergy of antibiotics against carbapenem-resistant P. aeruginosa.
Methods: The antibiotics minimum inhibitory concentration (MIC) was determined by the microbroth dilution method. Synergy effect of antibiotics was determined using the checkerboard assay without and with Resistance-Nodulation- Division (RND) efflux pump inhibitor phenylalanine-arginine betanaphthylamide (PAβN).
Results: The highest levels of synergistic effects found between cefepime/tobramycin and meropenem/tobramycin combinations in 35.3% of isolates. After adding PAβN, the most frequent synergistic effects between meropenem/ciprofloxacin and cefepime/ciprofloxacin combinations were found in 64.7%. The adding PAβN led to an increase in the synergy of all combinations except tobramycin/colistin. The highest effect of PAβN on synergy effects of antibiotics combination was observed in meropenem/ciprofloxacin, cefepime/ciprofloxacin and ciprofloxacin/colistin (increasing of 41.2%).
Conclusion: RND-efflux pump inhibition has a noticeable effect on the results of synergy tests of some antimicrobial agent combinations. Given the drug and strain-dependent effects of PAβN on synergy results, the effects of efflux pumps inhibitors should be studied on the different combinations drugs and on large population of bacterial strains.

Type of Manuscript: Experimental research article | Subject: Others

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