Clostridiumdifficile<br />By Kimberly Bowman, <br />Katie Lee, Michelle Shim<br />
Objectives<br />				Clostridiumdifficile<br />Epidemiology <br />Causes & Diagnosis <br />Treatment & Prevention <br />
Epidemiology<br />Katie Lee <br />
Morphology <br />Rod shaped<br />Gram positive<br />Anaerobic bacillus bacteria <br />Spore-forming<br />
Habitats<br />Soils<br />Marine Sediments <br />GI tract of Humans and other animals<br />Spores survive harsh conditions ...
Spore Survival<br />
Pathogenesis<br />Produces two exotoxins, A and B, which activate cytokines<br />Toxin A: Attracts the immune cells neutro...
Outbreak Strain<br />New virulence factors in NAP1 strain (NAP1/B1/027)<br />1. Binary toxin <br />     2. Fluoroquinolone...
Genetic Arrangement of Toxins<br /> <br />Voth, D.E. & Ballard, J.D. Clostridium difficile toxins: mechanism of action and...
Spore Germination<br />Agents that trigger spore germination:<br />Taurocholate (Bile salt)<br />Glycine <br />Lysozyme <b...
Comparative Phylogenomics<br /><ul><li>Multi-locus Sequence Typing (MLST) </li></ul>	- Mutation found to be 8x higher than...
Associated Diseases<br />C. difficile associated infection (CDI) <br />C. difficile associateddisease (CDAD)<br />Pseudome...
Causes & Diagnosis <br />Michelle Shim <br />
Causes<br />Contact with contaminated surfaces/items, then contact with mouth or nose<br />Nosocomially infected hospitals...
Symptoms & Recurrence<br />Watery diarrhea (at least 3 bowel movements per day for 2 or more days)<br />Fever<br />Loss of...
Diagnosis<br />Significant diarrhea (new onset of 3 or more partially formed or watery stool per 24 hour period)<br />Foul...
Diagnosis<br />Generally based on detection of toxin A or B<br />
Outbreak<br />2003: 2 outbreaks of highly virulent strain in Montreal and Calgary with deaths up to 89 people<br />2005: s...
Incidence<br />Poutanen, S. M. “Clostridium difficile-associated diarrhea in adults”. CMAJ. 2004. Canadian Medical Associa...
Risk factors<br />Age: > 65 years<br />Gender: female<br />Gastrointestinal surgery<br />Less than 1 year since admission ...
Treatment & Prevention<br />Kimberly Bowman<br />
Treatment for CDI<br />Asymptomatic Carriage<br />Treatment discouraged<br />Symptomatic Infection (CDAD & Colitis)<br />D...
Metronidazole vs Vancomycin<br />
Treatment for Symptomatic CDI<br />Stop Afflicting antibiotics<br />1st line: Metronidazole (Flagyl)<br />2nd line: Vancom...
Infection Control Measures<br />**The persistence of C diff spores is the biggest challenge in eradicating C diff from the...
Image from: Rupnik M, Wilcox MH and Gerding DN. Clostridium difficile Infection: new developments in epidemiology and path...
CDAD & Antibiotics<br />Almost all antibiotics have been correlated with increased incidence of C diff infection<br />Thos...
Antimicrobial Stewardship Programs<br />Goals: Reduce C diff incidence by monitoring usage of antibiotics esp. broad-spect...
Questions ?<br />
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Clostridium Difficile

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Clostridium Difficile

  1. 1. Clostridiumdifficile<br />By Kimberly Bowman, <br />Katie Lee, Michelle Shim<br />
  2. 2. Objectives<br /> Clostridiumdifficile<br />Epidemiology <br />Causes & Diagnosis <br />Treatment & Prevention <br />
  3. 3. Epidemiology<br />Katie Lee <br />
  4. 4. Morphology <br />Rod shaped<br />Gram positive<br />Anaerobic bacillus bacteria <br />Spore-forming<br />
  5. 5. Habitats<br />Soils<br />Marine Sediments <br />GI tract of Humans and other animals<br />Spores survive harsh conditions such as:<br /> - Acid human stomach<br /> - Disinfectant-treated hospital surfaces<br /> - Endoscopy equipment <br />
  6. 6. Spore Survival<br />
  7. 7. Pathogenesis<br />Produces two exotoxins, A and B, which activate cytokines<br />Toxin A: Attracts the immune cells neutrophils and monocytes <br />Toxin B: Degrades the epithelial cells of the colon; cause necrosis and inflammation of intestinal cells. <br />
  8. 8. Outbreak Strain<br />New virulence factors in NAP1 strain (NAP1/B1/027)<br />1. Binary toxin <br /> 2. Fluoroquinolone resistance <br />3. Deletion of tcdC gene <br />
  9. 9. Genetic Arrangement of Toxins<br /> <br />Voth, D.E. & Ballard, J.D. Clostridium difficile toxins: mechanism of action and role in disease. Clin. Microbiol. Rev. 18, 247–263 <br />
  10. 10. Spore Germination<br />Agents that trigger spore germination:<br />Taurocholate (Bile salt)<br />Glycine <br />Lysozyme <br />Thioglycolate<br />
  11. 11. Comparative Phylogenomics<br /><ul><li>Multi-locus Sequence Typing (MLST) </li></ul> - Mutation found to be 8x higher than recombination events<br /><ul><li>Microarray comparison among various strains </li></ul> - Genetic exchange readily available <br /> - Only 19.7% of DNA shared among strains <br />
  12. 12. Associated Diseases<br />C. difficile associated infection (CDI) <br />C. difficile associateddisease (CDAD)<br />Pseudomembranous colitis (PMC) <br />
  13. 13. Causes & Diagnosis <br />Michelle Shim <br />
  14. 14. Causes<br />Contact with contaminated surfaces/items, then contact with mouth or nose<br />Nosocomially infected hospitals, long-term care institutions<br />Broad range of antibiotic use<br />
  15. 15. Symptoms & Recurrence<br />Watery diarrhea (at least 3 bowel movements per day for 2 or more days)<br />Fever<br />Loss of appetite<br />Nausea<br />Abdominal pain or tenderness<br />Recurrance diarrhea – 5% to 40% of patients receiving treatment for C. difficile diarrhea<br />
  16. 16. Diagnosis<br />Significant diarrhea (new onset of 3 or more partially formed or watery stool per 24 hour period)<br />Foul stool odour<br />Colitis<br />Recent antibiotic exposure<br />
  17. 17. Diagnosis<br />Generally based on detection of toxin A or B<br />
  18. 18. Outbreak<br />2003: 2 outbreaks of highly virulent strain in Montreal and Calgary with deaths up to 89 people<br />2005: spread into Toronto and hospitalized 10, killing 1<br />2006: 21 deaths in Quebec; C. difficile mentioned on 6,480 death certificates in UK<br />2007: 4 killed and 14 cases in Mississauga<br />
  19. 19. Incidence<br />Poutanen, S. M. “Clostridium difficile-associated diarrhea in adults”. CMAJ. 2004. Canadian Medical Association. 10 Jan 2010. <http://www.cmaj.ca/cgi/content/full/171/1/51><br />
  20. 20. Risk factors<br />Age: > 65 years<br />Gender: female<br />Gastrointestinal surgery<br />Less than 1 year since admission to long-term care facility, hospital admission within 3 months of diagnosis<br />Serious underlying disease<br />Broad use of antibiotics (>3), esp. PPI, H2RA<br />
  21. 21. Treatment & Prevention<br />Kimberly Bowman<br />
  22. 22. Treatment for CDI<br />Asymptomatic Carriage<br />Treatment discouraged<br />Symptomatic Infection (CDAD & Colitis)<br />Depending on severity, treat with antibiotics<br />Pseudomembranous Colitis<br />Antibiotics and surgery <br />Recurrent CDAD<br />
  23. 23. Metronidazole vs Vancomycin<br />
  24. 24. Treatment for Symptomatic CDI<br />Stop Afflicting antibiotics<br />1st line: Metronidazole (Flagyl)<br />2nd line: Vancomycin <br />Others: Bacitracin, Fusidic Acid, Teicoplanin<br />Probiotics<br />Surgical: Colectomy<br />Fecal Bacteriotherapy<br />
  25. 25. Infection Control Measures<br />**The persistence of C diff spores is the biggest challenge in eradicating C diff from the hospital environment!<br />Isolation:<br />Full enteric precautions<br />Disinfection:<br />Hypocholrite substances<br />Hand Hygiene:<br />Soap and water recommended by CDC for CDAD<br />Education<br />
  26. 26. Image from: Rupnik M, Wilcox MH and Gerding DN. Clostridium difficile Infection: new developments in epidemiology and pathogenesis. Nature: July 2009: 7;526-536. <br />
  27. 27. CDAD & Antibiotics<br />Almost all antibiotics have been correlated with increased incidence of C diff infection<br />Those of greatest concern<br />Clindamycin<br />Cephalosporins (3rd and 4th generation)<br />Fluroquinolones<br />Broad Spectrum -lactams<br />
  28. 28. Antimicrobial Stewardship Programs<br />Goals: Reduce C diff incidence by monitoring usage of antibiotics esp. broad-spectrum antibiotics<br />After 2005 NAP1 outbreak in Quebec, antimicrobial stewardship program saw 54% reduction in antibiotics, 60% decrease in incidence<br />Implementing a program: key personnel<br />ID specialists<br />Multi professional team<br />
  29. 29. Questions ?<br />

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