Streptococcus pneumoniae response to repeated moxifloxacin or levofloxacin exposure in a rabbit tissue cage model
1Department of Pharmacy Research, Hartford Hospital, Hartford, Connecticut 06102, USA. dxuan@harthosp.org
Abstract:
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.
Insights
Moxifloxacin demonstrated superior bactericidal activity against Streptococcus pneumoniae compared to levofloxacin in a rabbit abscess model. Pharmacokinetic parameters, including AUC/MIC and peak/MIC ratios, correlated with antimicrobial efficacy for both fluoroquinolones.
Area of Science:
- Pharmacology
- Infectious Diseases
- Microbiology
Background:
- Fluoroquinolones, including moxifloxacin and levofloxacin, are critical for treating bacterial infections.
- Understanding the pharmacokinetic-pharmacodynamic (PK/PD) relationship is essential for optimizing antimicrobial efficacy and preventing resistance.
- Streptococcus pneumoniae is a significant pathogen, and fluoroquinolone resistance is a growing concern.
Purpose of the Study:
- To investigate the role of moxifloxacin and levofloxacin pharmacokinetics (PK) in antimicrobial efficacy against Streptococcus pneumoniae.
- To evaluate the impact of these antibiotics on the selection of fluoroquinolone-resistant S. pneumoniae strains.
- To compare the in vivo bactericidal activity and PK/PD relationships of moxifloxacin and levofloxacin.
Main Methods:
- A rabbit tissue cage abscess model was utilized to simulate human PK.
- Fluoroquinolone-sensitive S. pneumoniae was inoculated into the cages.
- Animals received varying oral doses of moxifloxacin or levofloxacin to achieve a range of PK exposures.
- Bacterial density and minimum inhibitory concentrations (MICs) were measured in abscess fluid over 14 days.
Main Results:
- Moxifloxacin regimens yielded higher area under the concentration-time curve (AUC)/MIC and peak/MIC ratios compared to levofloxacin.
- Both moxifloxacin and levofloxacin demonstrated rapid bactericidal activity in vivo.
- Moxifloxacin exhibited enhanced bactericidal activity and a greater reduction in bacterial load compared to levofloxacin at equivalent exposures.
- No development of fluoroquinolone resistance was observed for either drug within the study period.
Conclusions:
- Moxifloxacin and levofloxacin possess rapid in vivo bactericidal activity against S. pneumoniae.
- Moxifloxacin demonstrates superior antimicrobial efficacy compared to levofloxacin in this model.
- AUC/MIC and peak/MIC ratios are significant predictors of antimicrobial efficacy for both drugs.
- The study model did not induce the selection of fluoroquinolone-resistant S. pneumoniae strains with either moxifloxacin or levofloxacin treatment.
