title: Effect of cirrhosis on antibiotic efficacy in a rat model of pneumococcal pneumonia.
abstract: A rat model was used to study the effects of cirrhosis on antibiotic therapy of pneumococcal pneumonia. Cirrhotic and control male Sprague-Dawley rats were infected transtracheally with type 3 Streptococcus pneumoniae. Treatment began 18 h later with phosphate-buffered saline (PBS), azithromycin (50 mg/kg), trovafloxacin (50 mg/kg), or ceftriaxone (100 mg/kg) injected subcutaneously twice daily for 5 days. Antibiotic concentrations were measured by high-performance liquid chromatography. Azithromycin, trovafloxacin, and ceftriaxone were all equally effective at preventing mortality in both cirrhotic and normal rats. Free fraction area under the curve to minimum inhibitory concentration ratio (AUC/MIC) and maximum calculated serum concentration to MIC ratio (C(max)/MIC) and percent time that the serum concentration exceeded the MIC (%T > MIC) were greater for ceftriaxone compared with azithromycin or trovafloxacin. Azithromycin achieved higher concentrations in bronchoalveolar lavage fluid (BALF), epithelial lining fluid (ELF), and BAL white blood cells than ceftriaxone or trovafloxacin in cirrhotic rats. Macrolide, beta-lactam, or fluoroquinolone antibiotic efficacy in a pneumococcal pneumonia model does not appear to be affected by hepatic cirrhosis.
authors.affiliation: Infectious Diseases Section, Veterans Affairs Medical Center, Omaha, NE 68105, USA. laurel.preheim@med.va.gov
authors.forename: Laurel C
authors.initials: LC
authors.lastname: Preheim
authors.forename: Keith M
authors.initials: KM
authors.lastname: Olsen
authors.forename: Mei
authors.initials: M
authors.lastname: Yue
authors.forename: Mary U
authors.initials: MU
authors.lastname: Snitily
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Gentry-Nielsen
mesh_terms: D000818:Animals; D017963:Azithromycin / Q000494:pharmacology; D001682:Biological Availability; D001774:Blood Chemical Analysis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002443:Ceftriaxone / Q000494:pharmacology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D024841:Fluoroquinolones / Q000494:pharmacology; D007279:Injections, Subcutaneous; D008103:Liver Cirrhosis / Q000150:complications* / Q000473:pathology; D008297:Male; D009287:Naphthyridines / Q000494:pharmacology; D011018:Pneumonia, Pneumococcal / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015996:Survival Rate
chemical_list: D024841:Fluoroquinolones; D009287:Naphthyridines; D002443:Ceftriaxone; D017963:Azithromycin; C080163:trovafloxacin