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Antimicrobial Agents and Chemotherapy, October 2005, p. 4166-4173, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4166-4173.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Comparative Mutant Prevention Concentrations of Pradofloxacin and Other Veterinary Fluoroquinolones Indicate Differing Potentials in Preventing Selection of Resistance

H.-G. Wetzstein^*

Bayer HealthCare AG, Animal Health Division, 51368 Leverkusen, Germany

Received 25 May 2005/ Returned for modification 1 July 2005/ Accepted 15 July 2005

Pradofloxacin (PRA) is an 8-cyano-fluoroquinolone (FQ) being developed to treat bacterial infections in dogs and cats. Its mutant prevention concentrations (MPC) were determined for Escherichia coli ATCC 8739 at 0.225 µg/ml, and for Staphylococcus aureus ATCC 6538 at 0.55 µg/ml. At drug concentrations equal to or above the MPC, growth (implying selective clonal expansion) of first-step FQ-resistant variants, naturally present in large bacterial populations, was inhibited. MPC₉₀ derived from 10 clinical isolates each of E. coli and Staphylococcus intermedius, the latter species being of greater clinical relevance than S. aureus in companion-animal medicine, amounted to 0.2 to 0.225 and 0.30 to 0.35 µg/ml, respectively. MPCs of other veterinary FQs were assessed to determine relative in vitro potencies. The MPCs of marbofloxacin, enrofloxacin, danofloxacin, sarafloxacin, orbifloxacin, and difloxacin were 1.2-, 1.4-, 2.3-, 2.4-, 5-, and 7-fold higher than the MPC of PRA for E. coli ATCC 8739, and 6-, 6-, 19-, 15-, 15-, and 31-fold higher than the MPC of PRA for S. aureus ATCC 6538, respectively. MPC curves revealed a pronounced heterogeneity in susceptibility within populations of 4 x 10⁹ CFU employed, extending to 10-fold above the MICs. The duration of incubation and, for S. aureus, inoculum density profoundly affected the MPCs. With appropriate dosing, PRA may combine high therapeutic efficacy with a high potential for restricting the selection for FQ resistance under field conditions in the species analyzed.

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* Mailing address: Bayer HealthCare AG, Animal Health Division, Building 6700, Leverkusen 51368, Germany. Phone: 49 21 73 38 48 82. Fax: 49 21 73 38 35 02. E-mail: heinz-georg.wetzstein{at}bayerhealthcare.com.

This work is dedicated to G. Gottschalk, University of Göttingen, on the occasion of his 70th birthday.

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Antimicrobial Agents and Chemotherapy, October 2005, p. 4166-4173, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4166-4173.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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