A multidrug efflux pump inhibitor reduces fluoroquinolone resistance in Pseudomonas aeruginosa isolates

Abstract

In general, resistance to fluoroquinolones (FQs) in gram-negative bacteria is acquired either by mutations in DNA gyrase and topoisomerase IV or by active export of the agents via antibiotic efflux pumps. Reduced porin expression is also proposed to be another mechanism leading to resistance. In this study, interaction between levofloxacin, ofloxacin, and ciprofloxacin with MC-207,110 (multidrug efflux pump inhibitor) was investigated by a checkerboard assay using Pseudomonas aeruginosa. Levofloxacin, ofloxacin, and ciprofloxacin were tested at different concentrations (0.06-64 mug/ml) and MC-207,110 was tested at a concentration range of 4 - 128 mug/ml. In the presence of MC-207,110 (at 128, 64, 32, 16 mug/ml) resistance to FQs was inhibited significantly and MIC values were decreased, except at 8 and 4 mug/ml of MC-207,110. When MC-207,110 was used, resistance of P. aeruginosa to FQs in vitro was inhibited significantly, suggesting that MC-207,110 may be useful for use in clinical treatment protocols to overcome FQs resistance. Copyright (C) 2004 S. Karger AG, Basel.