Effect of ethanol on fluoroquinolone efficacy in a rat model of pneumococcal pneumonia.

Abstract

This investigation compared the effect of ethanol on fluoroquinolone antibiotic efficacy and pharmacodynamics in an ethanol-fed rat model of pneumococcal pneumonia. Male Sprague-Dawley rats received a liquid diet containing 36% of total calories as ethanol. Paired controls (pair-fed controls) were fed a liquid diet without ethanol or received rat chow. Diets began 7 days before and continued for 10 days after transtracheal infections with 10 times the 50% lethal dose of type 3 Streptococcus pneumoniae. Beginning 18 h after infection, the rats received once daily subcutaneous phosphate-buffered saline, levofloxacin, moxifloxacin, or trovafloxacin at 50 or 100 mg/kg of body weight. White blood cell counts were determined, blood samples were collected for culture, and mortality was recorded. Additional rats were killed on day 5 for pharmacodynamic studies and quantitative cultures of bronchoalveolar lavage fluid. Bacteremia occurred by day 3 in 20 of 22 untreated rats. All 22 untreated rats died by day 9. Moxifloxacin treatment was effective in all diet groups at both the 50- and 100-mg/kg doses. In contrast, 50-mg/kg doses of levofloxacin and trovafloxacin improved survival in ethanol-fed rats but were ineffective in chow-fed rats. High-dose trovafloxacin at 100 mg/kg was associated with increased mortality in pair-fed rats. The free-fraction area under the concentration-time curve/MIC ratio exceeded 50 with all antibiotics in the ethanol group but dropped below 30 with levofloxacin and trovafloxacin in the pair- and chow-fed rats, with higher mortality. Achievement of adequate antibiotic-free fraction area under the concentration-time curve/MIC ratios helps overcome ethanol-induced immune defects induced in experimental pneumococcal pneumonia.

• Authors: Keith M Olsen, Martha Gentry-Nielsen, Mei Yue, Mary U Snitily, Laurel C Preheim
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 50 Issue 1 Pg. 210-9 (Jan 2006) ISSN: 0066-4804 [Print] United States
• PMID: 16377688 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Anti-Bacterial Agents
• Fluoroquinolones
• Ethanol

Topics

• Animals
• Anti-Bacterial Agents (pharmacokinetics, therapeutic use)
• Bronchoalveolar Lavage Fluid (chemistry, cytology, microbiology)
• Disease Models, Animal
• Ethanol (adverse effects, pharmacology)
• Fluoroquinolones (pharmacokinetics, therapeutic use)
• Leukocyte Count
• Pneumonia, Pneumococcal (blood, drug therapy, metabolism)
• Rats
• Rats, Sprague-Dawley
• Streptococcus pneumoniae