This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wetzstein, H.-G. Search for Related Content PubMed PubMed Citation Articles by Wetzstein, H.-G.

 Previous Article  |  Next Article 

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

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.

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

This article has been cited by other articles:

• Silley, P., Stephan, B., Greife, H. A., Pridmore, A. (2007). Comparative activity of pradofloxacin against anaerobic bacteria isolated from dogs and cats. J Antimicrob Chemother 60: 999-1003 [Abstract] [Full Text]  
• Kehrenberg, C., de Jong, A., Friederichs, S., Cloeckaert, A., Schwarz, S. (2007). Molecular mechanisms of decreased susceptibility to fluoroquinolones in avian Salmonella serovars and their mutants selected during the determination of mutant prevention concentrations. J Antimicrob Chemother 59: 886-892 [Abstract] [Full Text]