title: 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 10(3) 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 10(3) 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.
authors.affiliation: Veterans Affairs Medical Center and the Department of Surgery, University of Louisville, Louisville, Kentucky 40206, USA.
authors.forename: Dustin R
authors.initials: DR
authors.lastname: Woods
authors.forename: Susan
authors.initials: S
authors.lastname: Heffley
authors.forename: James C
authors.initials: JC
authors.lastname: Peyton
authors.forename: William G
authors.initials: WG
authors.lastname: Cheadle
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001202:Ascitic Fluid / Q000166:cytology; D016470:Bacteremia / Q000382:microbiology; D002440:Cefoxitin / Q000008:administration & dosage*; D002908:Chronic Disease; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D007279:Injections, Subcutaneous; D007710:Klebsiella Infections / Q000188:drug therapy*; D007711:Klebsiella pneumoniae / Q000145:classification / Q000187:drug effects* / Q000254:growth & development; D007958:Leukocyte Count; D008168:Lung / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000473:pathology; D010538:Peritonitis / Q000188:drug therapy* / Q000382:microbiology; D011897:Random Allocation; D012703:Serotyping; D015996:Survival Rate; D015431:Weight Loss
chemical_list: D000900:Anti-Bacterial Agents; D002440:Cefoxitin