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

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

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

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

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

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

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.”

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

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…

CDI vs Antibiotic-Associated Diarrhea

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

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

Diagnosis

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”

85%-97%

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

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

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

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”

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

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

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

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

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

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

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

Hypervirulent CDI

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”

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

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

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

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:

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

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

“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

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

Clostridium difficile InfectionQuestions??