Background: P. aeruginosa exhibits several efflux pump systems that allow it to be
resistant to several antimicrobial agents. Phenylalanine arginyl β-naphthylamide
(PAβN) is an Efflux pump inhibitor (EPI) that can inhibit several multidrug efflux
pumps. Objective: This study aimed to detect the efflux pump activity in FQ resistant P.
aeruginosa, and to investigate the role of PAβN on FQ resistance. Methodology: P.
aeruginosa isolates were subjected to antibiotic susceptibility testing by disc diffusion
and those resistant to ciprofloxacin and levofloxacin were subjected to MIC detection
before and after addition of PAβN. Also reverse transcription RT PCR was done for
detection of mexA, mexC, mexE and mexX genes overexpression in the FQ resistant
strains. Results: After the addition of PAβN, 95.9% and 94.5% of the isolates showed
reduction in MICs of ciprofloxacin and levofloxacin respectively, 8.20% and 27.4% of
the isolates restored susceptibility to those drugs respectively and 8.20% reverted to
levofloxacin intermediate breakpoint. MexE was the most common efflux pump
overexpressed, followed by mexX and mexA. When using EPI 96.8% and 95.3% of the
isolates showed both overexpression and reduction of ciprofloxacin and levofloxacin
MIC respectively. Using a cut- off point of ≥4 fold reduction in levofloxacin MIC
discriminates efflux pump overexpressing from non-overexpressing isolates, (sensitivity
of 70%, specificity of 67%). Conclusion: Efflux pump mediated resistance is an
important mechanism contributing to multidrug resistance in P.aeruginosa as proven
phenotypically and genotypically, with mexE being the most commonly expressed. The
addition of PAβN to levofloxacin could be used as a phenotypic test for detection of
efflux pump overexpressing isolates and may be effective to restore the levofloxacin
susceptibility.
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