Antibiotic modulation in a clinically relevant model of chronic intraabdominal infection

Abstract

Continuous and twice-daily cefoxitin dosing was used in a highly lethal model of acute peritonitis in mice using intraperitoneal (IP) Klebsiella pneumoniae (Kpn). The purpose was to use antibiotics to create a model of chronic infection. Male Balb/c mice (averaging 20 g body weight) were inoculated IP with 103 colony-forming units (CFU) Kpn serotype 2. Controls received subcutaneous saline either twice daily or continuously. Antibiotic groups received 300 mg/kg per day of cefoxitin either twice daily or continuously. Survival and daily weight losses were determined. Another group was inoculated with 103 Kpn given twice daily saline or cefoxitin and harvested at 24 hours. Leukocyte counts were performed on peritoneal exudate cells (PEC) and peripheral blood. Cultures determined Kpn counts in blood, lung, and PEC. By 24 hours, saline-treated animals had lost more weight than cefoxitin mice (1 g vs. 2 g, P < 0.05). Continuous cefoxitin showed significant advantage with 50 per cent mortality at 5 days. Kpn levels were not significantly altered by cefoxitin. Cefoxitin treatment extended chronicity by preventing weight loss and increasing survival in a highly lethal, monomicrobial peritonitis model. This model will allow future study of specific host defense mechanisms over a prolonged time period.