Journal Article

Effect of 1-(1-naphthylmethyl)-piperazine, a novel putative efflux pump inhibitor, on antimicrobial drug susceptibility in clinical isolates of <i>Escherichia coli</i>

Winfried V. Kern, Petra Steinke, Anja Schumacher, Sabine Schuster, Heike von Baum and Jürgen A. Bohnert

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 57, issue 2, pages 339-343
Published in print February 2006 | ISSN: 0305-7453
Published online December 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki445
Effect of 1-(1-naphthylmethyl)-piperazine, a novel putative efflux pump inhibitor, on antimicrobial drug susceptibility in clinical isolates of Escherichia coli

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Objectives: 1-(1-Naphthylmethyl)-piperazine (NMP) has been shown to reverse multidrug resistance (MDR) in Escherichia coli overexpressing resistance–nodulation–cell division type efflux pumps, but there is no data on its activity in clinical isolates of E. coli.

Methods: The antimicrobial susceptibility of 60 clinical isolates of E. coli to a variety of antimicrobial agents was determined in the absence and presence of NMP and, for comparison, of Phe-Arg-β-naphthylamide (PAβN), another putative efflux pump inhibitor (EPI). The intracellular accumulation of ethidium bromide was measured to confirm efflux pump inhibition as the likely mechanism of action of NMP.

Results: Based on a 4-fold or greater reduction of the MIC after the addition of NMP in >50% of the isolates, significant effects of NMP at a concentration of 100 mg/L were seen for levofloxacin, linezolid and ethidium bromide. The ethidium bromide MIC changes after NMP addition correlated with differences in the ethidium bromide intracellular accumulation as measured by fluorometry in whole cell accumulation experiments. The activity of PAβN was different from that of NMP, in particular regarding macrolide resistance reversal, suggesting different modes of action of the two putative EPIs.

Conclusions: NMP is moderately active in reversing MDR in clinical isolates of E. coli and can partially restore fluoroquinolone susceptibility through inhibition of efflux pumps.

Keywords: multidrug resistance; fluoroquinolones; nosocomial pathogens

Journal Article.  2629 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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