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JAC Advance Access originally published online on November 30, 2005
Journal of Antimicrobial Chemotherapy 2006 57(1):104-109; doi:10.1093/jac/dki428
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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

In vitro activity of a novel compound, the metal ion chelating agent AQ+, against clinical isolates of Staphylococcus aureus

Benjamin R. D. Short, Miguel A. Vargas, Jonathan C. Thomas, Simon O'Hanlon and Mark C. Enright*

Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, Old Medical School Building, St Mary's Hospital, Norfolk Place, London W2 1PG, UK

Received 8 September 2005; returned 5 October 2005; revised 6 October 2005; accepted 1 November 2005

* Corresponding author. Tel: +44-207-5943417; Fax: +44-207-5943693; E-mail: m.c.enright{at}imperial.ac.uk

Objectives: To determine the efficacy of a novel antimicrobial compound, AQ+, against a genetically heterogeneous collection comprising 213 Staphylococcus aureus isolates from global sources. AQ+ is an aqueous preparation containing 0.5% 8-hydroxyquinoline.

Methods: MICs were found for all the isolates tested using the BSAC microdilution method. Time–kill studies were performed according to NCCLS guidelines. Transmission electron microscopy (TEM) was used to view the ultrastructural effects of AQ+.

Results: AQ+ was shown to strongly inhibit the growth of all isolates with a median MIC of 0.25% at a pH optimum of 9.2. Lowering the pH to 7.5 gave an ~4-fold reduction in efficacy and at pH 5.5 there was an ~8-fold reduction in efficacy. Methicillin-resistant S. aureus (MRSA) as well as vancomycin-intermediate S. aureus were shown to be as equally susceptible to AQ+ as methicillin-susceptible S. aureus. Time–kill curves for AQ+ were similar to those for gentamicin. TEM showed that AQ+ actively disrupts the cell wall of S. aureus leading to cell lysis.

Conclusions: These results suggest that AQ+ has strong antimicrobial activity and may be useful in preparations to reduce nasal and skin carriage of MRSA.

Keywords: 8-hydroxyquinoline , S. aureus , MRSA , time–kill , antimicrobial susceptibility


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