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Antimicrob Agents Chemother. Vancomycin Treatment's Association with Delayed Intestinal Tissue Injury, Clostridial Overgrowth and Recurrence of Clostridium difficile Infection in Mice
[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]
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Vancomycin Treatment's Association with Delayed Intestinal Tissue Injury, Clostridial Overgrowth and Recurrence of Clostridium difficile Infection in Mice
Cirle A. Warren, MD #, Edward J. Van Opstal, MSc, Mary S. Riggins, Yuesheng Li, MD, PhD, John H. Moore, MSc, Glynis L. Kolling, PhD, Richard L. Guerrant, MD and Paul S. Hoffman, PhD
Author Affiliations: Division of Infectious Diseases and International Health, University of Virginia, Charlottesville VA, US
ABSTRACT
Background:
Antibiotic treatment, including vancomycin, for Clostridium difficile infection (CDI) has been associated with recurrence of disease in up to 25%. This study investigates the effects of vancomycin on the clinical outcomes, intestinal histopathology and anaerobic community during and after treatment in a murine model of CDI.
Methods:
C57BL/6 mice were challenged with C. difficile strain VPI 10463 after pre-treatment with an antibiotic cocktail. Twenty-four hours after infection, mice were treated daily with vancomycin, nitazoxanide, fidaxomicin, or metronidazaole for 5 days. Mice were monitored for either 6 or 12 days post-infection. Clinical, diarrhea and histopathology scores were measured. Cecal contents or stool were assayed for clostridial or Bacteroides DNA and C. difficile toxin A/B.
Results:
Vancomycin treatment of infected mice was associated with improved clinical, diarrhea and histopathology scores and survival during treatment. However, after discontinuation of the drug, clinical scores and histopathology were worse in treated mice compared to untreated infected controls. At the end of the study, 62% of the vancomycin treated mice succumbed to recurrence, with an overall mortality rate equivalent to the untreated infected control group. Fidaxomicin-treated mice had similar outcomes to vancomycin-treated mice. C. difficile predominated over Bacteroides in cecal contents of vancomycin-treated mice similar to untreated infected mice. Decreasing duration of vancomycin treatment from 5 to 1 day decreased recurrence and deaths.
Conclusion:
Vancomycin improved clinical scores and histopathology acutely but was associated with poor outcome post treatment in C. difficile-infected mice. Decreasing vancomycin exposure may decrease relapse and improve survival in CDI.
FOOTNOTES
# Corresponding author: Cirle A. Warren, M.D., Division of Infectious Diseases and International Health, University of Virginia, 345 Crispell Drive, Charlottesville VA 22908, ca6t@virginia.edu.
Copyright ? 2012, American Society for Microbiology. All Rights Reserved.
-Author Affiliations: Division of Infectious Diseases and International Health, University of Virginia, Charlottesville VA, US
ABSTRACT
Background:
Antibiotic treatment, including vancomycin, for Clostridium difficile infection (CDI) has been associated with recurrence of disease in up to 25%. This study investigates the effects of vancomycin on the clinical outcomes, intestinal histopathology and anaerobic community during and after treatment in a murine model of CDI.
Methods:
C57BL/6 mice were challenged with C. difficile strain VPI 10463 after pre-treatment with an antibiotic cocktail. Twenty-four hours after infection, mice were treated daily with vancomycin, nitazoxanide, fidaxomicin, or metronidazaole for 5 days. Mice were monitored for either 6 or 12 days post-infection. Clinical, diarrhea and histopathology scores were measured. Cecal contents or stool were assayed for clostridial or Bacteroides DNA and C. difficile toxin A/B.
Results:
Vancomycin treatment of infected mice was associated with improved clinical, diarrhea and histopathology scores and survival during treatment. However, after discontinuation of the drug, clinical scores and histopathology were worse in treated mice compared to untreated infected controls. At the end of the study, 62% of the vancomycin treated mice succumbed to recurrence, with an overall mortality rate equivalent to the untreated infected control group. Fidaxomicin-treated mice had similar outcomes to vancomycin-treated mice. C. difficile predominated over Bacteroides in cecal contents of vancomycin-treated mice similar to untreated infected mice. Decreasing duration of vancomycin treatment from 5 to 1 day decreased recurrence and deaths.
Conclusion:
Vancomycin improved clinical scores and histopathology acutely but was associated with poor outcome post treatment in C. difficile-infected mice. Decreasing vancomycin exposure may decrease relapse and improve survival in CDI.
FOOTNOTES
# Corresponding author: Cirle A. Warren, M.D., Division of Infectious Diseases and International Health, University of Virginia, 345 Crispell Drive, Charlottesville VA 22908, ca6t@virginia.edu.
Copyright ? 2012, American Society for Microbiology. All Rights Reserved.
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