title: Prevalence of efflux-mediated ciprofloxacin and levofloxacin resistance in recent clinical isolates of Pseudomonas aeruginosa and its reversal by the efflux pump inhibitors 1-(1-naphthylmethyl)-piperazine and phenylalanine-arginine-β-naphthylamide.
abstract: To assess the prevalence of efflux-driven fluoroquinolone (FQ) resistance in recent clinical isolates of Pseudomonas aeruginosa, a worrisome and often hospital-acquired pathogen, 115 unique strains were collected over a 5-month period, of which 27 and 33 had decreased susceptibility to ciprofloxacin (CIP) and levofloxacin (LVX), respectively. The MIC(50) (minimum inhibitory concentration for 50% of the organisms) was 16 μg/mL for both FQs. The efflux pump inhibitors (EPIs) phenylalanine-arginine-β-naphthylamide (PAβN) and 1-(1-naphthylmethyl)-piperazine (NMP) were then used to evaluate their efficacy in reducing CIP and LVX MICs. NMP did not significantly modify CIP MICs, whilst PAβN resulted in MIC(50) values of 2 μg/mL and 0.125 μg/mL for CIP and LVX, respectively. With the addition of PAβN, susceptibility to CIP and LVX was recovered in 6 (22.2%) and 31 (93.9%) strains, respectively. The best combination to reverse FQ resistance in this set of strains was LVX with PAβN. The results of this study show that the effect of an EPI is not only dependent on the species on which it is used but also on the molecule associated with it. Therefore, the design of an EPI equally efficient on all resistance-nodulation-cell division (RND) efflux pumps appears to be difficult and, from a practical point of view, if an EPI is developed for clinical use, the efficiency of its combination with a definite molecule should be assessed carefully against a wide range of clinical isolates to evaluate the real benefit of this combination.
authors.affiliation: Laboratoire des Glucides, UMR-CNRS 6219, Équipe THÉRA, Faculté de Pharmacie, 1 rue des Louvels, Amiens cedex 1, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Sonnet
authors.forename: Daniel
authors.initials: D
authors.lastname: Izard
authors.forename: Catherine
authors.initials: C
authors.lastname: Mullié
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D024841:Fluoroquinolones / Q000494:pharmacology; D006801:Humans; D064704:Levofloxacin; D026901:Membrane Transport Proteins / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000494:pharmacology*; D000077489:Piperazine; D010879:Piperazines / Q000494:pharmacology; D015995:Prevalence; D011552:Pseudomonas Infections / Q000453:epidemiology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D004151:Dipeptides; D024841:Fluoroquinolones; D026901:Membrane Transport Proteins; D010879:Piperazines; C419365:phenylalanine arginine beta-naphthylamide; D000077489:Piperazine; D002939:Ciprofloxacin; D064704:Levofloxacin; D015242:Ofloxacin