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Antimicrobial Agents and Chemotherapy, February 2007, p. 744-747, Vol. 51, No. 2
0066-4804/07/$08.00+0     doi:10.1128/AAC.00334-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Relationship between Quinolone Exposures and Resistance Amplification Is Characterized by an Inverted U: a New Paradigm for Optimizing Pharmacodynamics To Counterselect Resistance{triangledown}

Vincent H. Tam,* Arnold Louie, Mark R. Deziel,{dagger} Weiguo Liu, and George L. Drusano

Emerging Infections and Host Defense Laboratory, Ordway Research Institute, Albany, New York

Received 17 March 2006/ Returned for modification 9 August 2006/ Accepted 31 October 2006

We determined the relationship between garenoxacin exposure and quinolone-resistant subpopulations for three bacterial isolates in an in vitro hollow-fiber infection model. An "inverted-U" relationship was identified wherein resistant subpopulations rose initially and then declined with increasing exposure, until reaching a threshold that prevented resistance amplifications. Different targets for the area under the concentration-time curve over 24 h/MIC ratio were required for different bacteria.

* Corresponding author. Mailing address: University of Houston College of Pharmacy, 1441 Moursund St., Houston, TX 77030. Phone: (713) 795-8316. Fax: (713) 795-8383. E-mail: vtam{at}uh.edu.

{triangledown} Published ahead of print on 20 November 2006.

{dagger} Deceased.

Antimicrobial Agents and Chemotherapy, February 2007, p. 744-747, Vol. 51, No. 2
0066-4804/07/$08.00+0     doi:10.1128/AAC.00334-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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