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JAC Advance Access published online on December 14, 2005
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki446
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© The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received August 30, 2005
Revised November 2, 2005
Accepted November 11, 2005

Brief report

Effect of 1-(1-naphthylmethyl)-piperazine, a novel putative efflux pump inhibitor, on antimicrobial drug susceptibility in clinical isolates of Enterobacteriaceae other than Escherichia coli

Anja Schumacher 1, Petra Steinke 1, Jürgen A. Bohnert 1, Murat Akova 2, Daniel Jonas 3, and Winfried V. Kern 1 *

1 Center for Infectious Diseases and Travel Medicine, Department of Medicine, University Hospital, Freiburg, Germany
2 Section of Infectious Diseases, Hacettepe University, Ankara, Turkey
3 Institute of Environmental Medicine and Hospital Epidemiology, University Hospital, Freiburg, Germany

* To whom correspondence should be addressed.
Winfried V. Kern, E-mail: kern{at}if-freiburg.de


  Abstract

Objectives: 1-(1-Naphthylmethyl)-piperazine (NMP) has been shown to reverse multidrug resistance (MDR) in Escherichia coli overexpressing RND type efflux pumps, but there is no data on its activity in Enterobacteriaceae other than E. coli.

Methods: The antimicrobial susceptibilities of laboratory strains and 167 clinical isolates of Enterobacteriaceae to a variety of antimicrobial agents were determined in the absence and presence of NMP and, for comparison, of Phe-Arg-{beta}-naphthylamide (PA{beta}N), another putative efflux pump inhibitor (EPI). A 4-fold or greater reduction of the MIC after EPI addition was considered significant.

Results: NMP consistently reduced the MIC of linezolid in Citrobacter freundii, Enterobacter aerogenes and Klebsiella pneumoniae clinical isolates. Significant effects of NMP addition in >50% of tested isolates were also seen for levofloxacin, tetracycline and chloramphenicol in E. aerogenes, and for levofloxacin and tetracycline in K. pneumoniae, whereas no or minor effects were observed in Serratia marcescens. MDR reversal by NMP was more likely in isolates with decreased susceptibility to fluoroquinolones. In most fluoroquinolone-resistant strains the activity was sufficient to render isolates drug-susceptible at clinically achievable concentrations. The activity of PA{beta}N was different from that of NMP, suggesting different modes of action of the two putative EPIs.

Conclusion: NMP has moderate activity in reversing MDR in many but not all members of the Enterobacteriaceae family including clinical isolates. Its effects on resistance reversal depend on bacterial species and drug, and are different from those seen with PA{beta}N.

Keywords: multidrug resistance; fluoroquinolones; nosocomial pathogens.
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