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Clostridium difficileBy Kimberly Bowman,
Katie Lee, Michelle Shim
Objectives
Clostridium difficile • Epidemiology • Causes & Diagnosis • Treatment & Prevention
EpidemiologyKatie Lee
Morphology
• Rod shaped• Gram positive• Anaerobic bacillus bacteria • Spore-forming
Habitats
• Soils• Marine Sediments • GI tract of Humans and other animals• Spores survive harsh conditions such as:
- Acid human stomach - Disinfectant-treated hospital surfaces - Endoscopy equipment
Spore Survival
Pathogenesis• Produces two exotoxins, A and B, which
activate cytokines• Toxin A: Attracts the immune cells neutrophils
and monocytes • Toxin B: Degrades the epithelial cells of the
colon; cause necrosis and inflammation of intestinal cells.
Outbreak Strain
• New virulence factors in NAP1 strain (NAP1/B1/027)1. Binary toxin
2. Fluoroquinolone resistance 3. Deletion of tcdC gene
Genetic Arrangement of Toxins
Voth, D.E. & Ballard, J.D. Clostridium difficile toxins: mechanism of action and role in disease. Clin. Microbiol. Rev. 18, 247–263
Spore Germination
Agents that trigger spore germination:
• Taurocholate (Bile salt)• Glycine • Lysozyme • Thioglycolate
Comparative Phylogenomics
• Multi-locus Sequence Typing (MLST) - Mutation found to be 8x higher than recombination events
• Microarray comparison among various strains - Genetic exchange readily available - Only 19.7% of DNA shared among strains
Associated Diseases
• C. difficile associated infection (CDI) • C. difficile associated disease (CDAD)• Pseudomembranous colitis (PMC)
Causes & Diagnosis Michelle Shim
Causes
• Contact with contaminated surfaces/items, then contact with mouth or nose
• Nosocomially infected hospitals, long-term care institutions
• Broad range of antibiotic use
Symptoms & Recurrence
• Watery diarrhea (at least 3 bowel movements per day for 2 or more days)
• Fever• Loss of appetite• Nausea• Abdominal pain or tenderness• Recurrance diarrhea – 5% to 40% of patients
receiving treatment for C. difficile diarrhea
Diagnosis
• Significant diarrhea (new onset of 3 or more partially formed or watery stool per 24 hour period)
• Foul stool odour• Colitis• Recent antibiotic exposure
Diagnosis
• Generally based on detection of toxin A or BLaboratory Test Advantages Disadvantages
Cytotoxin assay Excellent specificity Reduced sensitivity; 48h for results; requires special facility; detects only toxin B
Immunoassay Good specificity; < 4h for results; simple technique
Decreased sensitivity
Stool culture (with subsequent cytotoxin assay)
Excellent specificity and sensitivity
72-96h for results; labour intensive; requires special facility
Outbreak
• 2003: 2 outbreaks of highly virulent strain in Montreal and Calgary with deaths up to 89 people
• 2005: spread into Toronto and hospitalized 10, killing 1
• 2006: 21 deaths in Quebec; C. difficile mentioned on 6,480 death certificates in UK
• 2007: 4 killed and 14 cases in Mississauga
Incidence
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>
Risk factors
• Age: > 65 years• Gender: female• Gastrointestinal surgery• Less than 1 year since admission to long-term
care facility, hospital admission within 3 months of diagnosis
• Serious underlying disease• Broad use of antibiotics (>3), esp. PPI, H2RA
Treatment & Prevention
Kimberly Bowman
Treatment for CDI
• Asymptomatic Carriage– Treatment discouraged
• Symptomatic Infection (CDAD & Colitis)– Depending on severity, treat with antibiotics
• Pseudomembranous Colitis– Antibiotics and surgery
• Recurrent CDAD
Metronidazole vs VancomycinMetronidazole Vancomycin
Cost/Course $20 $800
Response > 95% > 95%
Route Oral or IV Oral only
Acts on Anaerobes Gram positives
Negatives Systemic side effects, some resistant strains of C diff
Promotes vancomycin-resistant bacteria [VRE], $$
Treatment for Symptomatic CDI
• Stop Afflicting antibiotics• 1st line: Metronidazole (Flagyl)• 2nd line: Vancomycin • Others: Bacitracin, Fusidic Acid, Teicoplanin• Probiotics• Surgical: Colectomy• Fecal Bacteriotherapy
Infection Control Measures
• Isolation:– Full enteric precautions
• Disinfection:– Hypocholrite substances
• Hand Hygiene:– Soap and water recommended by CDC for CDAD
• Education
**The persistence of C diff spores is the biggest challenge in eradicating C diff from the hospital environment!
Image from: Rupnik M, Wilcox MH and Gerding DN. Clostridium difficile Infection: new developments in epidemiology and pathogenesis. Nature: July 2009: 7;526-536.
CDAD & Antibiotics
• Almost all antibiotics have been correlated with increased incidence of C diff infection
• Those of greatest concern– Clindamycin– Cephalosporins (3rd and 4th generation)– Fluroquinolones– Broad Spectrum -lactams
Antimicrobial Stewardship Programs
• Goals: Reduce C diff incidence by monitoring usage of antibiotics esp. broad-spectrum antibiotics
• After 2005 NAP1 outbreak in Quebec, antimicrobial stewardship program saw 54% reduction in antibiotics, 60% decrease in incidence
• Implementing a program: key personnel– ID specialists– Multi professional team
Questions ?