Streptococcus pneumoniae response to repeated moxifloxacin or levofloxacinexposure in a rabbit tissue cage model

The role of moxifloxacin and levofloxacin pharmacokinetics (PK) in antimicr obial efficacy and in the selection of fluoroquinolone-resistant Streptococ cus pneumoniae strains was investigated using the rabbit tissue cage absces s model. A rabbit tissue cage was created by insertion of sterile Wiffle ba lls in the dorsal cervical area. Animals orally received a range of moxiflo xacin or levofloxacin doses that simulate human PK for 7 days 48 h after th e Wiffle balls were inoculated with fluoroquinolone-sensitive S. pneumoniae (10(7) 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 pr oduced AUC/MIC ratios of 5.1 to 85.5 and peak/MIC ratio of 0.9 to 14.8, Mox ifloxacin at 6.5, 26, and 42 mg/kg reduced the bacterial log CFU per millil iter 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 th e 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 o f 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 d evelop with any of the doses as assessed by a change in the MIC. In conclus ion, data derived from this study show that moxifloxacin and levofloxacin e xhibit rapid bactericidal activity against S, pneumoniae in vivo, and moxif loxacin exhibits enhanced bactericidal activity compared to levofloxacin, w ith 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.