Development of a Standardized Scoring System to Assess a Murine Model of Clostridium difficile Colitis. Issue 10 (25th November 2020)

• Record Type: Journal Article
• Authors: Shelby, Rita D.; Tengberg, Natalie; Conces, Miriam; Olson, Jacob K.; Navarro, Jason B.; Bailey, Michael T.; Goodman, Steven D.; Besner, Gail E.
• Is Part Of: Journal of investigative surgery. Volume 33:Issue 10(2020)
• Page Start: 887
• Page End: 895
• Publication Date: 2020-11-25
• Subjects: C. difficile -- colitis -- model -- mouse -- scoring system; Surgery -- Research -- Periodicals; Research; Surgery; Surgical Procedures, Operative; 617.075
• DOI: 10.1080/08941939.2019.1571129
• Languages: English
• ISSNs: 0894-1939

Abstract

Abstract: Background: Clostridium difficile infection is the most common cause of antimicrobial-associated diarrhea. Our aim was to introduce a novel and efficient clinical sickness score (CSS), and to define a detailed histologic injury score (HIS) in a murine model of C. difficile colitis. Methods: Mice received an antibiotic cocktail (kanamycin, gentamicin, colistin, metronidazole, and vancomycin) for 96 h. After 48 h, mice received an intraperitoneal injection of clindamycin, followed by oral C. difficile (1.5 × 10 7 CFU). Signs of sickness were scored using a novel CSS (range 0–12) with scores ≥6 consistent with C. difficile colitis. Intestinal tissue was analyzed utilizing an adapted HIS (range 0–9) with scores ≥4 consistent with C. difficile colitis. Stool was analyzed for C. difficile, and survival evaluated. Results: No control mice showed signs of sickness, whereas 23% of mice receiving antibiotics alone and 65% of mice exposed to antibiotics and subsequently C. difficile demonstrated signs of sickness ( p = 0.0134). No control mice had histologic injury, whereas 8% of mice receiving antibiotics alone and 75% of mice exposed to antibiotics followed by C. difficile had evidence of histologic injury ( p = 0.0001). Mice exposed to C. difficile lost more weight, although not significant ( p = 0.070). Mice that received C. difficile had decreased survival compared to control mice and mice receiving antibiotics only ( p = 0.03). Conclusions: We have developed a novel clinical scoring system, and detailed histological grading system, that enables the objective evaluation of a murine C. difficile colitis model. This model allows the study of this disease in a host that demonstrates clinical and histologic signs comparable to human C. difficile infection. This will allow for improved study of therapeutics for this disease in the future.