1. A Mouse Model of Clostridium difficile–Associated Disease
Xinhua Chen, Kianoosh Katchar, Jeffrey D. Goldsmith, Nanda Nanthakumar, Adam Cheknis, Dale N. Gerding, Ciarán P. Kelly 
Gastroenterology 
Volume 135, Issue 6, Pages (December 2008)
DOI: /j.gastro
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2. Figure 1
Experimental design schematics. (A) Different durations of pretreatment with the antibiotic mixture (14, 7, 3, or 0 days) before clindamycin and C difficile (VPI10463) challenge, (B) different challenge doses of C difficile (2 × 102, 103, 104, 105 cfu), (C) use of vancomycin for 5 days immediately after C difficile challenge (104 cfu), and (D) rechallenging survivors from groups E and F.
Gastroenterology  , DOI: ( /j.gastro )
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3. Figure 2
Kaplan–Meier survival plots for mice exposed to different durations of antibiotic pretreatment (14, 7, 3, or 0 days) and subsequently challenged with C difficile VPI10463 (105 cfu, n = 12 per group).
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2008 AGA Institute Terms and Conditions

4. Figure 3
Kaplan–Meier survival plots for mice infected with different doses of C difficile VPI10463 (2 × 102, 103, 104, 105 cfu) after 3 days of antibiotic pretreatment and a single dose of clindamycin (n = 12 per group except n = 24 for the 105 group).
Gastroenterology  , DOI: ( /j.gastro )
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5. Figure 4
Histologic examination of colonic tissues obtained from antibiotic-treated mice exposed to C difficile showed (A) proliferative ulcerative enteritis with superficial epithelial necrosis and release of inflammatory exudates and necrotic cellular material into the intestinal lumen, (B) marked submucosal edema without submucosal inflammation, and (C) mucosal proliferation, epithelial necrosis, and presence of inflammatory cells, which are composed predominantly of neutrophils.
Gastroenterology  , DOI: ( /j.gastro )
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6. Figure 5
(A) Kaplan–Meier survival plots of antibiotic-treated mice exposed to C difficile (104 cfu on day 0) and treated with vancomycin (solid line) or vehicle (dashed line) for 5 days (day 0 to day 4 inclusive) (n = 12 per group). Vehicle-treated mice showed morbidity from day 2 onward and 50% died from CDAD by day 4. Vancomycin-treated mice showed no signs of disease during treatment and all survived to day 10. However, from day 11 onward, the vancomycin-treated mice showed evidence of CDAD and 58% died by day 15. (B) Mean relative weight of all surviving mice (up to the day of death) in the vancomycin-treated (○) and control (●) groups. The control group showed significant weight loss at day 2 and reached their lowest level on day 3, after which the weight of the surviving mice (50%) increased and returned to normal by day 9. In contrast, vancomycin-treated mice had no weight loss during the first 9 days after C difficile inoculation. However, weight loss became evident on day 10 and reached a nadir on days 11 and 12, after which the average weight of the surviving mice (42%) quickly increased to reach normal by day 15. Data stand for mean relative weight ± standard error. Day 3: vehicle, 80.2 ± 1.3; vancomycin, ± 0.4 (P < .01). Day 12: vehicle, ± 0.6; vancomycin, 85.0 ± 4.5 (P < .01). Day 15: vehicle, ± 0.7; vancomycin, ± 4.6 (P = .5).
Gastroenterology  , DOI: ( /j.gastro )
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7. Figure 6
(A) Relative weight graph of mice challenged with various strains of C difficile including K14, BI1, BI17, and VPI strains at the dose of 105 cfu, from day 0 to day 5 (mean relative weight ± standard error; N = 8 per group). Relative weight is based on the weight at day 0. For animals that died, their terminal weights were extrapolated to the end of the experiment. Both the VPI and BI17 groups showed more weight loss than the K14 and BI1 groups. (On day 5, the mean relative weight for VPI vs BI1, P < .001; VPI vs K14, P < .001; BI17 vs BI1, P < .001; and BI17 vs K14, P < .001.) (B) Pathologic score of colon from mice challenged with various strains of C difficile. The histologic severity of enteritis was graded taking into account the following features: epithelial cell damage, neutrophil margination, hemorrhagic congestion, and edema of the mucosa. The total score of the VPI10463 group was 7.0 ± 0 (N = 3); K14 group was 1.3 ± 0.5 (N = 4); BI1 group was 4.4 ± 1.1; BI17 group was 4.5 ± 0.5; and the negative control group was 1.3 ± 0.7. VPI vs negative control, P = .001; VPI vs K14, P < .001; BI1 vs negative control, P = .1; BI1 vs K14, P = .05; B17 vs negative control, P = .01; B17 vs K14: P < .01.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2008 AGA Institute Terms and Conditions