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JAC Advance Access published online on November 30, 2005
Journal of Antimicrobial Chemotherapy, 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
Received September 8, 2005
Revised October 6, 2005
Accepted November 1, 2005

Original article

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

Benjamin R. D. Short 1, Miguel A. Vargas 1, Jonathan C. Thomas 1, Simon O'Hanlon 1, and Mark C. Enright 1 *

1 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

* To whom correspondence should be addressed.
Mark C. Enright, E-mail: m.c.enright{at}imperial.ac.uk


  Abstract

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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