Clostridium difficile (anaerobic)

Question 1

Disease

Answer 1

• antibiotic-associated pseudomembranous
  colitis
• common nosocomial (hospital-acquired) cause of diarrhea.

Question 2

Transmission

Answer 2

• organism colonizes large intestine
• most people not colonized-> most people take antibiotics don’t get pseudomembranous colitis.
• Transmitted by fecal–oral route.
• Spores or bacterial
  organism transmitted.

Question 3

Pathogenesis

Answer 3

• Antibiotics suppress drug-sensitive members of normal flora of colon, allowing C. difficile to multiply & produce exotoxins A & B glucosyltransferases (enzymes glucosylate
  G protein Rho GTPase).
• Exotoxin B depolymerizes
  actin-> loss of cytoskeletal integrity, apoptosis, & death of enterocytes.
• Clindamycin 1st antibiotic cause of pseudomembranous colitis, but many antibiotics
  cause disease.
• 3rd gen cephalosporins common cause, frequently used.
• Ampicillin & fluoroquinolones
  implicated.
• cancer chemotherapy predisposes to pseudomembranous
  colitis.
• rarely invades intestinal mucosa.

Question 4

Clinical Findings

Answer 4

• diarrhea associated with pseudomembranes
  (yellow-white plaques) on colonic mucosa
• not bloody diarrhea & neutrophils found in stool
• Fever & abdominal pain.

Organism rarely enters blood stream & causes metastatic infection.

• pseudomembranes visualized by sigmoidoscopy.
• Toxic megacolon
• surgical resection
  of colon necessary.
• Pseudomembranous colitis distinguished from transient diarrhea-> oral antibiotics side effect by testing presence of toxin in stool.
• Hypervirulent strain-> more severe disease, recurrences, responds less well to metronidazole than previous strain.
• resistance to quinolones -> widespread use of quinolones for diarrheal
  disease

Question 5

Lab Diagnosis

Answer 5

• Exotoxins presence in filtrate of patient’s stool
  specimen
• insufficient-> people can be colonized by organism & not have disease.

2 types of tests

1) Detects exotoxin itself
- ELISA test employing antibody to exotoxin is used.
2) Detects genes that encode exotoxin.
- PCR assay to determine the presence of toxin gene DNA

• DNA-based test greater sensitivity & specificity than ELISA.
• NAAT tests interpreted with caution-> colonized by C. difficile & be positive when not cause of disease.

Question 6

Treatment

Answer 6

• causative antibiotic withdrawn.
• Oral metronidazole
  or vancomycin given & fluids replaced.
• Metronidazole preferred -> VRE
• life-threatening cases, vancomycin used-> more effective
• life-threatening cases, surgical colon removal
• treatment does not eradicate carrier state & recurrent episodes of colitis occur.

Fidaxomicin (Dificid) ->
pseudomembranous colitis & preventing relapses & effective in life-threatening cases.

• Fecal transplantation-> administering bowel flora from normal individual by enema or nasoduodenal
  tube to patient with pseudomembranous colitis= bacterial interference (replace C. difficile with normal bowel flora).
• High cure rates; aesthetic considerations limited acceptance.

Question 7

Prevention

Answer 7

• no vaccines or drugs.
• antibiotics-> predisposing factor for pseudomembranous
  colitis->prescribed only when necessary.
• Hospital, strict infection control procedures-> rigorous handwashing.

Probiotics(Saccharomyces)useful to prevent pseudomembranous colitis.