Effect of cirrhosis on antibiotic efficacy in a rat model of pneumococcal pneumonia

Laurel C. Preheim, Keith M. Olsen, Mei Yue, Mary U. Snitily, Martha J. Gentry-Nielsen

Research output: Contribution to journalArticle

4 Scopus citations

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 (Cmax/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, β-lactam, or fluoroquinolone antibiotic efficacy in a pneumococcal pneumonia model does not appear to be affected by hepatic cirrhosis.

Original languageEnglish (US)
Pages (from-to)103-111
Number of pages9
JournalDiagnostic Microbiology and Infectious Disease
Volume51
Issue number2
DOIs
StatePublished - Feb 2005

Keywords

  • Antibiotic efficacy
  • Cirrhosis
  • Pneumococcal pneumonia

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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