Comparative efficacies of azithromycin and ciprofloxacin against experimental Salmonella typhimurium infection in mice

Azithromycin was compared with ciprofloxacin for the treatment of established intracellular infection with Salmonella typhimurium LT-2 in CF-1 mice. For studies of mortality, mice received five times the LD50 of organisms intraperitoneally and were given drugs intragastrically once daily for seven days. For studies of in-vivo antibacterial activity, splenic viable counts were measured in mice that had received 0.5 times the intraperitoneal LD50 and had been given drugs for three days. The MICs of azithromycin and ciprofloxacin, respectively, against LT-2 were 4.0 and 0.03 mg/L. The 50% protective doses of the drugs required to prevent mortality were azithromycin 24.7 mg/kg/day, and ciprofloxacin 30.2 mg/kg/day. Treatment with azithromycin and ciprofloxacin in doses of 25 and 100 mg/kg/day resulted in reduction of mean log10 cfu per spleen. Splenic concentrations of azithromycin up to 8 h after treatment exceeded its MIC against the LT-2 strain, whereas serum levels were less than the MIC. These results indicated that azithromycin given orally once daily was as effective as ciprofloxacin against established murine Salmonella infection and that the efficacy of azithromycin correlated with adequate tissue concentrations of antibiotic.