Streptococcus pneumoniae response to repeated moxifloxacin or levofloxacin exposure in a rabbit tissue cage model.
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 (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 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.
Xuan
D
D
Department of Pharmacy Research, Hartford Hospital, Hartford, Connecticut 06102, USA. dxuan@harthosp.org
Zhong
M
M
Mattoes
H
H
Bui
K Q
KQ
McNabb
J
J
Nicolau
D P
DP
Quintiliani
R
R
Nightingale
C H
CH
D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001372:Aza Compounds; D004195:Disease Models, Animal; D005260:Female; D024841:Fluoroquinolones; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D000077266:Moxifloxacin; D015242:Ofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology*; D011008:Pneumococcal Infections / Q000378:metabolism; D011804:Quinolines; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000187:drug effects*
D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D064704:Levofloxacin; D015242:Ofloxacin; D000077266:Moxifloxacin