1. What’s All the Fuss About Clostridium difficile? Peter C. Iwen, PhD, D(ABMM) Nebraska Public Health Laboratory

2. Clostridium difficile – GI Disease Indigenous microflora of colon 1 trillion bacteria per gram!

4. Objectives l C. difficile ….the organism l Host relationships and pathogenesis l Diagnosis l Prevention and control l Patient management l Update clinical issues

5. National Estimates of US Short-Stay Hospital Discharges with C. difficile as First-Listed or Any Diagnosis From McDonald LC, et al. Emerg Infect Dis. 2006;12(3):409-15

6. Clostridium difficile l Bacterium –Anaerobe –Gram-positive spore-forming bacillus l Source –Environment –Stool flora

7. Host Relationship Disturbed colonic microflora ↓ C. difficile exposure & colonize ↓ Toxin A & B ↓ Diarrhea & colitis

8. Risk Factors l Age >65 years l Severe underlying disease –Prompting hospitalization l Nasogastric intubation l Antiulcer medications –Proton pump inhibitors l Antimicrobial therapy –Clindamycin, 3 rd generation cephalosporins, penicillin, fluoroquinolones l Long hospital stay or long-term care residency “Clostridium difficile is the most common cause of nosocomial infectious diarrhea.”

9. Sunenshine and McDonald,Cleveland Clin. J. Med., Feb 2006

10. Virulence Factors l Toxin A –Exotoxin –Enterotoxic to cells l Toxin B –Exotoxin –Not as toxic to cells? l Multiple strains of C. difficile –ToxA+/ToxB+ –ToxA+/ToxB- –ToxA-/ToxB+ …only toxigenic strains of C. difficile produce disease…

11. CDI vs Antibiotic-Associated Diarrhea

12. Clinical Presentation l Mild disease –Non-bloody diarrhea –Mild abdominal tenderness l Severe disease –Pseudomembranous colitis –Paralytic ileus l Ileitis –Toxic megacolon l Ulcerative colitis –Perforation –Ascites

13. Pseudomembranous Colitis H & E, OM 400x Mushroom-shaped pseudomembrane→ “Volcano” lesion Yellow lesion against hyperemic bowel

14. Diagnosis

15. Diagnostics l Generally…. …if stool samples are obtained after hospital day 3, the only enteric pathogen most labs will test for is…..Clostridium difficile….. l Testing not considered a STAT test –Batching, but calling all positive results l Many labs will only test a diarrheic stool specimen l Follow-up testing of previous positive result not useful –Patients remain positive for months –Not useful for “proof-of-cure”

16. 85%-97%

17. Relative Sensitivity Culture > Cell cytotoxin > Toxin A & B EIA > Toxin A EIA > Latex agglutination > Endoscopy

18. What about PCR? l Studies have shown PCR to be less sensitive than the toxin assay –Requires a nucleic acid extraction step l Complexity of stool matrix a problem

19. CDI Case Defined l Stool characteristic –Diarrhea (most common) –No diarrhea l Associated with toxic megacolon or ileitis –Documented by radiology l ≥ 1 of the following –Stool positive for: l C. difficile toxin l C. difficile determined to be a toxin producer –Pseudomembranous colitis by: l Endoscopy l Histological exam

20. Prevention and Control l Prevent ingestion of the organism –Infection control strategies l Target environment l Personal hygiene l Barrier methods l Reduce the chance of disease in the event of such digestion –Minimize or eliminate antibiotic exposure l “Good antimicrobial stewardship”

21. Audience Interaction l Clostridium difficile spores can resist desiccation and can persist on hard surfaces: A.48 hours or less B.About 1 week C.About 1 month D.> 6 months

22. l The most effective cleaning agent for killing C. difficile spores in the environment is: A.70% alcohol B.10% bleach C.Hot water and soap D.Phenol solutions E.Quaternary ammonium compounds Enhanced environmental cleaning…sporocidal

23. l The incubation period for Clostridium difficile infection is: A.Less than 1 day B.1-7 days C.2-3 weeks D.Unknown

24. l Barrier precautions to prevent the spread of Clostridium difficile include: A.Airborne precautions B.Droplet precautions C.Contact precautions D.Standard precautions only Single room GlovesGowns Duration of isolation controversial …2 days after diarrhea resolves …upon discharge

25. Patient Management Surgical consult…perforation, toxic megacolon, colonic-wall thickening, ascites….

26. “Stool infusion therapy” or “fecal transplant” has been shown to be highly effective….

27. Update Clinical Issues l Hypervirulent C. difficile strain l Community-associated CDI l Proton Pump Inhibitors as risk factor –Antacids and antiulcer drugs l Medicare issues and CDI

28. Hypervirulent CDI

29. Hypervirulent C. difficile Strain l North American PFGE Type 1 l Restriction enzyme analysis Type BI l PCR ribotype 027 Collectively referred to as “NAP1/BI/027 strain”

30. NAP1 Virulence Attributes l Hypertoxigenic –Toxin A16x –Toxin B23x –Binary toxin l Hypersporulation capacity l High-level resistance to fluoroquinolones –Leads to outbreaks

31. States with the Epidemic Strain of C. difficile Confirmed by CDC and Hines VA labs (N=24), Updated 2/9/2007 DC PR AK HI

32. Community-Acquired CDI l Less common than nosocomial l No traditional risk factors –“Spontaneous” l Exposure to hypervirulent strain l More likely to receive antacids (anti-ulcer) drugs

34. Heartburn Drugs Cause Diarrhea? l Proton pump inhibitors –Prilosec –Prevacid –Nexium l H2 blockers –Zantac –Pepcid –Tagamet l Main function is to suppress stomach acid production –Gastritis –GERD (acid reflux disease) –Heartburn S. Dial, 2005, J. Amer. Med Assoc., 293:2989-2995.

35. Stomach Acid-Suppressing Medications and Community-Acquired CDAD, England From Dial S, et al. JAMA. 2005;294:2989-2995.

36. Deficit Reduction Act of 2005 l Requires an adjustment in Medicare Diagnosis Related Group payments l –For certain hospital-acquired conditions

38. “Myth Busters” l C. difficile may infect individuals who are NOT taking antibiotics l Optimal method to diagnose CDI is NOT clear l Alcohol-based gels are NOT effective for hand hygiene against C. difficile spores l Vancomycin is NOT the recommended initial therapy for CDI l Current literature does NOT support the use of probiotics to treat for CDI l CDI is NOT only a problem in acute care hospital facilities but also long-term care and rehab centers

39. Recommendations for Control l Conduct surveillance for CDI l Early diagnosis and treatment l Strict infection control practices l Good antimicrobial stewardship

40. Clostridium difficile InfectionQuestions??