Treatment of Wound Sepsis in Irradiated Mice

Abstract

Infections in the immunocompromised host are difficult to treat. The local and systemic effect of penicillin therapy, supplemented by immunoglobulins, and pentoxifylline on wounds infected by Staphylococcus aureus was evaluated in mice irradiated with 6.5 Gy 60Co gamma-rays. Three days after irradiation a suspension of S. aureus was inoculated subcutaneously over the gluteus muscle of anesthetized mice. The skin and the muscle were incised at the site of the inoculation. Treatment with 62.5 mg/kg penicillin-G was administered for 10 days. Numbers of bacteria per mg muscle and presence of organisms in spleens and livers were determined. Numbers of bacteria were significantly reduced from 7.3 (+/- 0.3) to 5.3 (+/- 0.4) log10 CFU/mg (+/- SEM) muscle in treated animals. Administration of immunoglobulin G i.v. or pentoxifylline i.p. alone, or in addition to penicillin-G, did not further reduce the number of bacteria. Increase in the dose of penicillin to 250 mg/kg decreased the number of bacteria more than 62.5 mg/kg. Bacteria were recovered from spleens and/or livers of all 13 untreated mice, and only in six of the 13 penicillin-treated mice (P less than 0.05). Penicillin therapy reduced the systemic spread of S. aureus. The model provides a means to evaluate regimens for treatment of bacterial wound infections in irradiated animals. The data illustrated the ability of antimicrobial agents to contain but not cure the infection in the immunocompromised host, and the lack of efficacy of immunoglobulins in neutropenic mice.