Comparative efficacies of ceftriaxone, moxalactam, and ampicillin in experimental Salmonella typhimurium infection

Abstract

The activities of ceftriaxone, moxalactam, and ampicillin against Salmonella typhimurium LT-2 were compared in culture media at pH 5, 6, 7 and 8 and in mice inoculated intraperitoneally. The minimal inhibitory concentrations for strain LT-2 in Mueller-Hinton broth were 0.03 microgram of ceftriaxone per ml, 0.08 microgram of moxalactam per ml, and 0.4 microgram of ampicillin per ml. A comparison of minimal inhibitory concentrations in buffered broth at pH 5 with those in media at higher pH values showed that ceftriaxone was more acid stable than the other antibiotics. Groups of CF-1 female mice inoculated intraperitoneally with 3 X 10(4) colony-forming units received saline or each drug in fourfold decremental doses by the subcutaneous route every 8 h for 3 days, beginning at 24 h after challenge. The mean log 10 colony-forming units of S. typhimurium per spleen at the end of treatment and the mortality rates at 21 days after inoculation were measured for each treatment group. The mean log 10 colony-forming units per spleen was significantly reduced from that of the saline control by dosages of greater than or equal to 0.06 mg of ceftriaxone per kg, 64 mg of moxalactam per kg, or greater than or equal to 16 mg of ampicillin per kg (P less than 0.05). Mortality rates of infected mice were significantly reduced by dosages of greater than or equal to 1 mg of ceftriaxone per kg or greater than or equal to 64 mg of ampicillin per kg (P less than 0.05), whereas moxalactam in dosages as high as 16 mg/kg did not significantly reduce mortality rate. These results demonstrate the superiority of ceftriaxone to the other tested antibiotics on a weight basis in this model of experimental Salmonella infection.