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Antimicrobial Agents and Chemotherapy, March 2003, p. 1096-1100, Vol. 47, No. 3
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.3.1096-1100.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Mechanism of Fluoroquinolone Resistance Is an Important Factor in Determining the Antimicrobial Effect of Gemifloxacin against Streptococcus pneumoniae in an In Vitro Pharmacokinetic Model

Alasdair P. MacGowan* and Karen E. Bowker

Bristol Centre for Antimicrobial Research and Evaluation,1 University of Bristol,2 North Bristol NHS Trust, Department of Medical Microbiology, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, United Kingdom3

Received 22 January 2002/ Returned for modification 16 September 2002/ Accepted 15 November 2002

Antibacterial effect and emergence of resistance to gemifloxacin and levofloxacin were studied in an in vitro pharmacokinetic model of infection. A panel of Streptococcus pneumoniae strains with known mechanisms of resistance were used; two strains had no known resistance mechanism, two had efflux pumps, three had gyrA plus parC mutations, and one had only a parC mutation. Gemifloxacin MICs were in the range of 0.016 to 0.25 mg/liter, and levofloxacin MICs ranged from 1 to 16 mg/liter. Antimicrobial effect was measured by area under the bacterial-kill curve up to 72 h, and emergence of resistance was determined by population analysis profile before and during drug exposure. The area under the curve (AUC)/MIC ratios for gemifloxacin and levofloxacin were 35 to 544 and 3 to 48, respectively. As expected on the basis of these AUC/MIC ratio differences, antibacterial effect was much greater for gemifloxacin than levofloxacin. In the gemifloxacin simulations, mechanism of resistance as well as MIC determined the antibacterial effect, as indicated by gemifloxacin’s greater effect against efflux strains compared to those with gyrA or parC mutations despite similar MICs. This was not true of levofloxacin. Emergence of resistance was not easily demonstrated with either agent, and mechanism of resistance did not have any impact on it.

* Corresponding author. Mailing address: Bristol Centre for Antimicrobial Research and Evaluation, Department of Medical Microbiology, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, United Kingdom. Phone: 44 (0) 1179595652. Fax: 44 (0) 1179593154. E-mail: macgowan_a{at}southmead.swest.nhs.uk.

Antimicrobial Agents and Chemotherapy, March 2003, p. 1096-1100, Vol. 47, No. 3
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.3.1096-1100.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Firsov, A. A., Lubenko, I. Y., Smirnova, M. V., Strukova, E. N., Zinner, S. H. (2008). Enrichment of Fluoroquinolone-Resistant Staphylococcus aureus: Oscillating Ciprofloxacin Concentrations Simulated at the Upper and Lower Portions of the Mutant Selection Window. Antimicrob. Agents Chemother. 52: 1924-1928 [Abstract] [Full Text]  
  • Odenholt, I., Cars, O. (2006). Pharmacodynamics of moxifloxacin and levofloxacin against Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli: simulation of human plasma concentrations after intravenous dosage in an in vitro kinetic model. J Antimicrob Chemother 58: 960-965 [Abstract] [Full Text]  
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