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

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 - Jan 1 2005

Fingerprint

Pneumococcal Pneumonia
Azithromycin
Ceftriaxone
Fibrosis
Anti-Bacterial Agents
Dimercaprol
Lactams
Fluoroquinolones
Macrolides
Bronchoalveolar Lavage Fluid
Microbial Sensitivity Tests
Streptococcus pneumoniae
Serum
Liver Cirrhosis
Area Under Curve
Sprague Dawley Rats
Leukocytes
Phosphates
High Pressure Liquid Chromatography
Mortality

Keywords

  • Antibiotic efficacy
  • Cirrhosis
  • Pneumococcal pneumonia

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Effect of cirrhosis on antibiotic efficacy in a rat model of pneumococcal pneumonia. / Preheim, Laurel C.; Olsen, Keith Melvin; Yue, Mei; Snitily, Mary U.; Gentry-Nielsen, Martha J.

In: Diagnostic Microbiology and Infectious Disease, Vol. 51, No. 2, 01.01.2005, p. 103-111.

Research output: Contribution to journalArticle

Preheim, Laurel C. ; Olsen, Keith Melvin ; Yue, Mei ; Snitily, Mary U. ; Gentry-Nielsen, Martha J. / Effect of cirrhosis on antibiotic efficacy in a rat model of pneumococcal pneumonia. In: Diagnostic Microbiology and Infectious Disease. 2005 ; Vol. 51, No. 2. pp. 103-111.
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