zithromax and Liver-Cirrhosis

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.

Topics: Animals; Azithromycin; Biological Availability; Blood Chemical Analysis; Bronchoalveolar Lavage Fluid; Ceftriaxone; Disease Models, Animal; Drug Therapy, Combination; Fluoroquinolones; Injections, Subcutaneous; Liver Cirrhosis; Male; Naphthyridines; Pneumonia, Pneumococcal; Random Allocation; Rats; Rats, Sprague-Dawley; Reference Values; Risk Assessment; Sensitivity and Specificity; Survival Rate

The pharmacokinetics of azithromycin were determined over a 192-h period following oral administration of a single 500-mg dose to six healthy volunteers and to 16 cirrhotic patients (ten class A and six class B; Pugh's classification). Plasma and urinary levels were determined by microbiological assay. The mean Cmax, obtained 2-3 h after administration, was 0.29 mg/L in volunteers, and 0.39 and 0.51 mg/L in class A and class B cirrhosis, respectively. The elimination half-life was 53.5 h in control subjects, and 60.6 and 68.1 h in class A and class B cirrhotic patients, respectively. The mean residence time was significantly higher in class B patients, but AUC, Vd, Cltot and Clr values appeared to be similar in all groups. The mean urinary recovery of azithromycin at 192 h varied from 11-15.7%, and did not differ significantly among groups. These results demonstrate that azithromycin pharmacokinetics do not differ consistently in patients with mild or moderate hepatic impairment in comparison with healthy volunteers. Therefore, no dosage modifications of azithromycin seem to be required for patients with class A or B liver cirrhosis.

Topics: Adult; Aged; Azithromycin; Erythromycin; Female; Half-Life; Humans; Liver; Liver Cirrhosis; Male; Middle Aged; Tissue Distribution