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JAC Advance Access originally published online on May 21, 2009
Journal of Antimicrobial Chemotherapy 2009 64(2):359-363; doi:10.1093/jac/dkp172
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© The Author 2009. 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

Evaluation of the mutant selection window for fluoroquinolones against Neisseria gonorrhoeae

George P. Allen* and Cynthia D. Hankins{dagger}

Oregon State University College of Pharmacy at Oregon Health and Science University, Portland, OR 97239-4501, USA

Received 23 November 2008; returned 29 January 2009; revised 6 April 2009; accepted 20 April 2009

* Corresponding author. Tel: +1-503-494-5976; Fax: +1-503-494-8797; E-mail: allenge{at}ohsu.edu

Objectives: The availability of antimicrobials that may be used for the treatment of infections caused by Neisseria gonorrhoeae has been limited by the emergence of antimicrobial resistance, particularly fluoroquinolone resistance. Few data exist regarding the pharmacodynamics of fluoroquinolone resistance selection in N. gonorrhoeae.

Methods: We used mutant prevention concentration (MPC) testing to define the risk of fluoroquinolone resistance induction in N. gonorrhoeae by ciprofloxacin, levofloxacin and moxifloxacin in a wild-type isolate (ATCC 49226) and its corresponding gyrA mutant (m-49226).

Results: MIC/MPC values (mg/L) of ciprofloxacin, levofloxacin and moxifloxacin for ATCC 49226 were 0.0078/0.03125, 0.0078/0.125 and 0.0156/0.0625, respectively. The MIC of all fluoroquinolones for m-49226 was 0.125 mg/L; MPCs of ciprofloxacin, levofloxacin and moxifloxacin for this isolate were 4, 0.5 and 0.25 mg/L, respectively. Concentrations of all agents are predicted to exceed the MPC for ATCC 49226 for the entire dosage interval, while concentrations of moxifloxacin alone will exceed the MPC for m-49226. The hierarchy of tested agents with respect to %TMSW [percentage of the dosage interval that concentrations fall within the mutant selection window (MSW)] for m-49226 was ciprofloxacin > levofloxacin > moxifloxacin. Multiple-dose fluoroquinolone regimens are predicted to achieve superior pharmacodynamics in comparison with single-dose regimens for m-49226, with increased AUC/MPC values and a reduced %TMSW.

Conclusions: Evaluation of the use of moxifloxacin against N. gonorrhoeae is warranted, as is use of multiple-dose fluoroquinolone regimens.

Keywords: antimicrobial pharmacodynamics , antimicrobial resistance , mutant prevention concentration

{dagger} Present address: Providence St Vincent Medical Center, 9205 SW Barnes Road, Portland, OR 97225, USA


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