Effect of Efflux Pump Inhibitor 1-(1-naphthylmethyl)-piperazine to Mic Values of Ciprofloxacin in Ciprofloxacin Resistant Gram-Negative Bacteria

Abstract

Effective efflux pump systems play a crucial role in the development of multiple antimicrobial resistance in bacteria. In this study, the effects of an efflux pump inhibitor 1 -(1 -naphthylmethyl)-piperazine on ciprofloxacin (CIP) minimum inhibitory concentration (MIC) values in gram-negative bacteria including Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae were investigated. Nineteen CIP-resistant P.aeruginosa, 37 extended spectrum beta-lactamase (ESBL) positive E.coli and 13 ESBL positive K.pneumoniae clinical isolates were included to the study. CIP MIC values of each isolate were determined by broth microdilution method as recommended by CLSI. MIC values were determined also in the presence of 100 μg/ml NMP. CIP MICs for all isolates were 4 μg/ml or higher. In the presence of 100 μg/ml NMP, CIP MICs did not change for P.aeruginosa isolates. While MICs decreased > 4-fold for 22 (59.4%) E.coli isolates, 2-fold decrease was detected only for 14 (37.8%) isolates. MIC value did not change for 1 isolate. While MICs decreased ≥ 4-fold for 10 (76.9%) K.pneumoniae isolates, ≥ 2-fold decrease was detected for 3 (23.1%) isolates. In conclusion, while NMP consistently reduced the MIC of ciprofloxacin in E.coli and K.pneumoniae clinical isolates, no effects was observed in P.aeruginosa isolates.