Clostridium difficile as a Nosocomial Pathogen

1
Clostridium difficile as a Nosocomial Pathogen

• Elizabeth Wu
• Bacteriology 330
• April 26, 2007

2
Clostridium difficile

• Gram-positive bacillus
• Spore-forming
• Anaerobic
• Most common nosocomial infection of GI tract

3
Cause?

• Healthy people good bacteria keeps bad under
  control.
• Antibiotics kill both the good and bad bacteria ?
  C. difficile growth

4
Antibiotics

• Virtually all antibiotics can cause infection
• Most common antibiotics
• Ampicillin
• Amoxicillin
• Cephalosporins
• Clindamycin

5
C. difficle-associated diseases (CDAD)

• Pseudomembranous colitis (PMD)
• Antibiotic-associated diarrhea (AAD) (15-25)
• Perforation of the colon
• Toxic megacolon
• Sepsis
• Death (rarely)

6
Disease Symptoms

• Appear within 4-10 days of taking antibiotics or
• weeks after discontinuing medication
• Watery diarrhea
• Fever
• Loss of appetite
• Nausea
• Abdominal pain

7
C. difficile colonization

• Different from C. difficile diseases no apparent
  symptoms
• Patients test positive for the bacterium/toxin
• More common than CDADs

8
Transmission

• Transmitted through feces
• Bathtubs, toilets, and rectal thermometers
  reservoirs for spores
• Enter body via mouth or mucous membranes
• healthcare workers working with different
  patients

9
Pathology

• C. difficile spores germinate in small intestine
• Polysaccharide capsule prevents phagocytosis
• Bacteria multiplies in colon
• Binds to intestinal wall
• Inflammation of colon

10
Virulence Factors

• Major virulence factors
• Enterotoxin toxin A (TcdA)
• Cytotoxin toxin B (TcdB)
• Binary toxin (CDT)
• Encoded by two genes cdtA and cdtB
• Pathogenic role not known

11
Virulence Factors

• Adhesins
• Relevance in colon not yet determined
• Enzymes
• May play role in survival in intestine
• S-layer
• Outer cell coat

12
TcdA and TcdB

• enter intestinal epithelial cells by endocytosis
• disrupt actin cytoskeleton ? cell death
• Induce production of Tumor Necrosis Factor
  (TNFa), proinflammatory interleukins (IL-1)
• Degrade at room temperature

13
TcdA

• Causes necrosis, increased intestinal
  permeability, and inhibition of protein
  synthesis.
• Affects phospholipase A2
• Produces prostaglandins and
• Leukotrienes
• Eventually leads to erosion of mucosa
• Viscous, bloody fluid produced

14
TcdB

• No noticeable enterotoxic activity
• Lethal in vitro
• May be effective after intestinal wall has been
  damaged

15
Diagnostic Tests

• Colonoscopy
• Sigmoidoscopy
• Toxin Test
• Enzyme immunoassay (toxin A, B, or both) same
  day results
• Tissue cytotoxicity assay (toxin B) more
  sensitive results within 24-48 hours

16
Diagnostic Tests

• Stool sample
• Most sensitive results within 48-96 hours
• Toxin undetectable within 2 hours of collection
• False-positive results appear with non-toxigenic
  strains
• Antigen detection
• results within 1 hour
• Detects presence of C. difficile antigen
• results compared with toxin test to verify
  diagnosis

17
Whos at risk?

• Elderly
• People staying in a hospital or nursing home
• People taking antibiotics
• People with compromised immune systems
• Patients who recently had gastrointestinal
  surgery

18
Treatment

• 23 CDADs resolve within 2-3 days after
  discontinuing antibiotics
• 10 days of (oral) Metronidazole and Vancomycin
• Surgery to remove infected parts of intestine

19
Prevention

• Only take antibiotics if necessary
• Wash hands with soap and water or alcohol based
  hand-soap after using restroom and before eating
• Wash contaminated materials/surfaces with warm
  water and detergent or disinfectant

20
Prevention

• If there is an outbreak, do NOT use alcohol-based
  hand-soap
• Healthcare workers should wear gloves when
  treating infected patients

21
Recent outbreaks

• Emergence of new strain in last 2 years
• Diagnostic tests do not differentiate between
  strains
• Produces 16-23 times greater amounts of toxins A
  and B
• More resistant against fluoroquinolones
• Metranidazole recommended for treatment

22
References

• Barbut, Frederic, Beatrice Gariazzo, Laetitia
  Bonne, Valerie Lalande, Beatrice Burghoffer,
  Ralucca Luiuz, and Jean-Claude Petit. "Clinical
  Features of Clostridium Difficile-Associated
  Infections and Molecular Characterizations of
  Strains Results of a Retrospective Study,
  2000-2004." Infection Control and Hospital
  Epidemiology 28.2 (2007) 131-139. PubMed. 20
  Mar. 2007.
• McDonald, L. Clifford, Bruno Coignard, Erik
  Dubberke, Xiaoyan Song, Teresa Horan, Preeta K.
  Kutty, and Ad Hoc Clostridium Diffic .
  "Recommendations for Surveillance of Clostridium
  Difficile-Associated Disease." Infection Control
  and Hospital Epidemiology 28.2 (2007) 140-145.
  20 Mar. 2007.
• McDonald, L. Clifford. "Clostridium Difficile
  Responding to a New Threat From an Old Enemy."
  Infection Control and Hospital Epidemiology os
  26.8 (2005) 672-674. 10 Mar. 2007
  .
• Paxton, I. R., J. McCoubrey, and G. Blair. "The
  Pathogenicity of Clostridium Difficile." Clinical
  Microbiology and Infection the Official
  Publication of the European Society of Clinical
  Microbiology and Infectious Diseases 7.8 (2001)
  421-427. PubMed. 21 Mar. 2007.
• Reineke, Jessica, Stefan Tenzer, Maja Rupnik ,
  Andreas Koschinski, Oliver Hasselmayer, Andre
  Schrattenholz, Hansjorg Schild, and Christoph Von
  Eichel-Streiber. "Autocatalytic Cleavage of
  Clostridium Difficile Toxin B." Nature ns (2007)
  1-5. PubMed. 20 Mar. 2007.
• Surawicz, Christina M. "Antibiotics and
  Clostridium Difficile Cause and Cure." Journal
  of Clinical Gastroenterology ns 41.1 (2007) 1-2.
  Journals_at_Ovid. 20 Mar. 2007.