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JAC Advance Access originally published online on December 4, 2008
Journal of Antimicrobial Chemotherapy 2009 63(2):349-352; doi:10.1093/jac/dkn493
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© The Author 2008. 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

Original research

Paradoxical effect of 1-(1-naphthylmethyl)-piperazine on resistance to tetracyclines in multidrug-resistant Acinetobacter baumannii

D. C. Bean1 and D. W. Wareham1,2,*

1 Centre for Infectious Disease, Institute of Cell and Molecular Science, Barts and The London, Queen Mary's School of Medicine and Dentistry, London, UK 2 Division of Infection, Barts and The London NHS Trust, London, UK

Received 6 October 2008; returned 28 October 2008; revised 7 November 2008; accepted 7 November 2008

* Corresponding author. Centre for Infectious Disease, Institute of Cell and Molecular Science, 4 Newark Street, Whitechapel, London E1 2AT, UK. E-mail: d.w.wareham{at}qmul.ac.uk

Objectives: The efflux inhibitor 1-(1-naphthylmethyl)-piperazine (NMP) has been demonstrated to reverse multidrug resistance in Acinetobacter baumannii. We investigated the interaction of NMP with tigecycline and three other tetracyclines on clinical isolates of A. baumannii.

Methods: One hundred and four clinical isolates of Acinetobacter were tested for susceptibility to tigecycline, minocycline, doxycycline and tetracycline by disc diffusion, and tigecycline MICs were determined by Etest, both in the presence and absence of NMP. Tigecycline MICs and zones of inhibition were interpreted using the BSAC guidelines. An OXA carbapenemase multiplex PCR was also performed on each isolate.

Results: Mean zones of inhibition for tetracycline, doxycycline and minocycline increased by 11.3%, 22.9% and 11.2%, respectively, in the presence of NMP. In contrast, tigecycline susceptibility was decreased in the presence of NMP, with mean zones of inhibition decreasing by 8.4%. Based on PCR results, all but six isolates belonged to the OXA-23 clone 1.

Conclusions: Susceptibility to tigecycline of the A. baumannii OXA-23 clone 1 prevalent in the UK is reduced (~2-fold) by the presence of the efflux inhibitor NMP. NMP does not have the same effect on susceptibility to other tetracyclines.

Keywords: Acinetobacter , tigecycline , efflux inhibitor


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D. W. Wareham, N. C. Gordon, J. B. Casals, and D. C. Bean
Reduced susceptibility of multidrug-resistant Acinetobacter baumannii to tigecycline in combination with 1-(1-naphthylmethyl)-piperazine is not a pH-dependent phenomenon
J. Antimicrob. Chemother., May 1, 2009; 63(5): 1075 - 1076.
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