Investigation of the Effect of Efflux Pump Inhibitors to MIC Values of Ciprofloxacin in Clinical Isolates of Pseudomonas Aeruginosa, Escherichia Coli, Acinetobacter Baumannii and Staphylococcus Aureus

Abstract

The aim of this study was to investigate the effects of efflux pump inhibitors on the minimal inhibitory concentration (MIC) values of ciprofloxacin (CIP) in fluoroquinolone-resistant 42 Pseudomonas aeruginoso (n=42), Escherichia coli (n=97), Acinetobacter baumannii (n=58) and Staphylococcus aureus (n=80) strains isolated from clinical specimens. For this purpose phenylalanyl-arginyl-beta-naphthylamide (PAßN) was used for P.aeruginosa, E.coli, A.baumonnii and reserpine for S.aureus isolates as pump inhibitors. Fluoroquinolone resistance of the clinical isolates were determined by VITEK2 Compact (BioMerieux, France) automated system and confirmed with standard broth microdilution method. For the investigation of the effects of inhibitor agents, the MIC values were also determined in the presence of 25 μg/ml and 100 μg/ml PAßN and 20 μg/ml reserpine. In the presence of 25 mg/l PAßN, 61.9% of CIP resistant P.aeruginosa strains converted to susceptible ones, while this rate was 73.8% in the presence of 100 mg/l PAßN. In A.boumannii clinical isolates, 8.6% and 15.5% of CIP-resistant strains have become susceptible in the presence of 25 mg/l and 100 mg/l PAßN, respectively. Similarly the MIC values for CIP have decreased ≥ 4 folds in 42.2%, and ≥ 2 folds in 30.9% of E.coli isolates, in the presence of 25 mg/l PAßN, however, there was no change in MICs of 26.9% of E.coli strains. The MIC values have also been lowered for ≥ 4 folds in 83.6%, and two folds in 13.4% of E.coli strains by the use of 100 mg/l PAßN concentration, however, no decrease in MIC values was detected in 3% of the isolates. 20 mg/l of reserpine have caused a decrease of ≥ 4 folds in 8.75%, and two folds in 33.75% of S.aureus isolates, while there was no change in MIC values of 57.5% of S.aureus strains. Our results showed that PAßN causes significant reduction in MIC values for CIP in the clinical isolates of P.aeruginoso, E.coli and A.boumannii and this effect may be attributed to efflux pump inhibition. In contrast, it was concluded that reserpine does not have a considerable effect on the MIC values of S.aureus against ciprofloxacin.