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Antimicrobial Agents and Chemotherapy, April 2004, p. 1215-1221, Vol. 48, No. 4
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.4.1215-1221.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Pharmacodynamics of Moxifloxacin and Levofloxacin at Simulated Epithelial Lining Fluid Drug Concentrations against Streptococcus pneumoniae

Naomi R. Florea,1 Pamela R. Tessier,2 Cuilian Zhang,2 Charles H. Nightingale,2,3 and David P. Nicolau2,4*

Loma Linda University School of Pharmacy, Loma Linda, California,1 Center for Anti-Infective Research and Development,2 Office of Research Administration,3 Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut4

Received 24 July 2003/ Returned for modification 26 November 2003/ Accepted 24 December 2003

Recent clinical failures associated with levofloxacin treatment for Streptococcus pneumoniae infections and growing evidence of frequent mutations in the isolate population have led to increased concerns regarding fluoroquinolone resistance. Our objective was to characterize the efficacies of levofloxacin and moxifloxacin against various genotypes of S. pneumoniae after simulated bronchopulmonary exposures. An in vitro model was used to simulate a levofloxacin concentration of 500 mg and a moxifloxacin concentration of 400 mg, which were previously determined to be the concentrations in the epithelial lining fluid of older adults receiving once-daily dosing. The effects of the drugs were tested against six S. pneumoniae containing various mutations. Bacterial density and resistance were quantitatively assessed over 48 h. The S. pneumoniae isolate with no mutation displayed a 4-log reduction in CFU after treatment with both agents and did not develop resistance. Isolates containing the parC or parE mutation or both mutations regrew and developed resistance when they were exposed to levofloxacin, despite an unbound area under the concentration-time curve (AUC):MIC ratio of ~100. When the isolate containing the parC and gyrA mutations was exposed to levofloxacin, there was a half-log reduction in the number of CFU compared to that for the control, but the isolate subsequently regrew. Likewise, levofloxacin did not kill the isolate containing the parC, gyrA, and parE mutations. Moxifloxacin sustained the killing of all bacterial isolates tested without the development of resistance. Levofloxacin did not sustain bacterial killing and did not prevent the emergence of further resistance in mutants with the parC or parE mutation or both mutations, even though an unbound AUC:MIC ratio for exposure well above the breakpoint of 30 to 40 established in the literature for S. pneumoniae was maintained. Moxifloxacin was effective against all isolates tested, despite the presence of isolates with two- and three-step mutations, for which the MICs were increased.

* Corresponding author. Mailing address: Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour St., Hartford, CT 06102. Phone: (860) 545-3941. Fax: (860) 545-3992. E-mail: dnicola{at}harthosp.org.

Antimicrobial Agents and Chemotherapy, April 2004, p. 1215-1221, Vol. 48, No. 4
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.4.1215-1221.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Homma, T., Hori, T., Sugimori, G., Yamano, Y. (2007). Pharmacodynamic Assessment Based on Mutant Prevention Concentrations of Fluoroquinolones To Prevent the Emergence of Resistant Mutants of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 51: 3810-3815 [Abstract] [Full Text]  
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