title: Ethanol feeding does not affect the efficacy or pharmacokinetics of azithromycin, trovafloxacin, or ceftriaxone in a rat model of pneumococcal pneumonia.
abstract: A rat model of ethanol feeding was used to study the effects of ethanol on antibiotic therapy of pneumococcal pneumonia. Male Sprague-Dawley rats (150 g) received a liquid diet containing 36% of total calories as ethanol. Controls were pair-fed a liquid diet without ethanol or received rat chow. Diets began 7 days pre- and continued postinfection. Rats were infected transtracheally with type 3 Streptococcus pneumoniae and then treated with azithromycin (50 mg/kg), trovafloxacin (50 mg/kg), or ceftriaxone (100 mg/kg) injected subcutaneously twice daily for 5 days. Antibiotic levels in serum, lung cells, and lavage fluid were measured by HPLC. Ethanol- and pair-fed rats had depressed baseline peripheral neutrophil counts but were able to generate adequate numbers of peripheral and pulmonary polymorphonuclear leukocytes early in the course of their infection. Ethanol feeding did not alter the pharmacokinetics of azithromycin, trovafloxacin, or ceftriaxone. All three antibiotics were equally effective in curing experimental pneumococcal pneumonia, and survival rates were similar in treated ethanol-fed and control rats.
authors.affiliation: Infectious Diseases Section, Veterans Affairs Medical Center, Creighton University School of Medicine, Omaha, Nebraska 68105, USA. preheim@omaha.va.gov
authors.forename: L C
authors.initials: LC
authors.lastname: Preheim
authors.forename: K M
authors.initials: KM
authors.lastname: Olsen
authors.forename: M
authors.initials: M
authors.lastname: Yue
authors.forename: M U
authors.initials: MU
authors.lastname: Snitily
authors.forename: M J
authors.initials: MJ
authors.lastname: Gentry
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D017963:Azithromycin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000382:microbiology; D002443:Ceftriaxone / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005247:Feeding Behavior / Q000502:physiology*; D024841:Fluoroquinolones; D007958:Leukocyte Count; D008297:Male; D009287:Naphthyridines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009504:Neutrophils; D011018:Pneumonia, Pneumococcal / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D000431:Ethanol; D002443:Ceftriaxone; D017963:Azithromycin; C080163:trovafloxacin