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Antimicrobial Agents and Chemotherapy, March 2001, p. 794-799, Vol. 45, No. 3
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.3.794-799.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Streptococcus pneumoniae Response to Repeated Moxifloxacin or Levofloxacin Exposure in a Rabbit Tissue Cage Model

Dawei Xuan,1,* Mingkang Zhong,1 Holly Mattoes,1 Khanh Q. Bui,1 Jocarol McNabb,1 David P. Nicolau,1,2 Richard Quintiliani,2 and Charles H. Nightingale1,3

Department of Pharmacy Research,1 Division of Infectious Diseases,2 and Office of Research Administration,3 Hartford Hospital, Hartford, Connecticut 06102

Received 7 June 2000/Returned for modification 21 October 2000/Accepted 23 December 2000

The role of moxifloxacin and levofloxacin pharmacokinetics (PK) in antimicrobial efficacy and in the selection of fluoroquinolone-resistant Streptococcus pneumoniae strains was investigated using the rabbit tissue cage abscess model. A rabbit tissue cage was created by insertion of sterile Wiffle balls in the dorsal cervical area. Animals orally received a range of moxifloxacin or levofloxacin doses that simulate human PK for 7 days 48 h after the Wiffle balls were inoculated with fluoroquinolone-sensitive S. pneumoniae (107 CFU). Abscess fluid was collected on a daily basis over 14 days to measure bacterial density and MICs. Moxifloxacin regimens produced a range of area under the concentration-time curve (AUC)/MIC ratios ranging from 9.2 to 444 and peak/MIC ratios ranging from 1.3 to 102. Levofloxacin doses produced AUC/MIC ratios of 5.1 to 85.5 and peak/MIC ratio of 0.9 to 14.8. Moxifloxacin at 6.5, 26, and 42 mg/kg reduced the bacterial log CFU per milliliter in abscess fluid (percentage of that in a sterile animal) by 4.2 ± 2.2 (20%), 5.8 ± 0.4 (100%), and 5.4 ± 0.4 (100%), respectively, over the dosing period. Levofloxacin at 5.5, 22, and 32 mg/kg reduced the log CFU per milliliter in abscess fluid (percentage of that in a sterile animal) by 2.8 ± 0.7 (20%), 5.1 ± 1.3 (80%), and 4.6 ± 1.3 (60%), respectively. Moxifloxacin has a greater bactericidal rate as determined by regression of log CFU versus time data. The AUC/MIC and peak/MIC ratios correlated with the efficacy of both drugs (P < 0.05). Resistance to either drug did not develop with any of the doses as assessed by a change in the MIC. In conclusion, data derived from this study show that moxifloxacin and levofloxacin exhibit rapid bactericidal activity against S. pneumoniae in vivo, and moxifloxacin exhibits enhanced bactericidal activity compared to levofloxacin, with AUC/MIC and peak/MIC ratios correlated with antimicrobial efficacy for both drugs. The development of fluoroquinolone-resistant S. pneumoniae was not observed with either drug in this model.

* Corresponding author. Mailing address: Pharmacy Research, Hartford Hospital, 80 Seymour St., Hartford, CT 06102. Phone: (860) 545-3612. Fax: (860) 545-3992. E-mail: dxuan{at}harthosp.org.

Antimicrobial Agents and Chemotherapy, March 2001, p. 794-799, Vol. 45, No. 3
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.3.794-799.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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