1. Clostridium difficileinfectionClinical presentation and complications
Dr Vu Kwan
Staff Specialist
Department of Gastroenterology
Westmead Hospital

2. Case presentation
3. Mr HL
72 year old male
Background:
Ischaemic heart disease
NSTEMI 2009
Coronary stent
Echocardiogram: EF 25%
Atrial fibrillation
Warfarin
Chronic kidney disease
Baseline creatinine ~180
4. October 2009
Per rectum bleeding
Admitted for observation
Discharged for outpatient colonoscopy
Recurrent bleeding
Admitted for inpatient colonoscopy
Colonoscopy:
Multiple large colonic polyps
Endoscopic mucosal resection performed
Histology
Multiple tubular adenomas
Invasive malignancy not excluded
5. 6. 7. 8. Post-polypectomy
Represented 3 days post-procedure with recurrent rectal bleeding
ED assessment:
Post-polypectomy bleeding
Possible peptic ulcer bleeding
Commenced on high dose proton-pump inhibitor infusion
Observed for several days bleeding cessation
Discharged home
9. Representation
Represented 2 days later with bloody diarrhoea
Up to 10 episodes per day
Initially assumed to be ongoing post-polypectomy bleeding
No stool tests performed
10. Colonoscopy
Pseudomembranous colitis
11. History
No history of recent antibiotics
Only history:
Elderly male
Multiple co-morbidities
Repeated hospitalisations
Only new medication = PPI
12. Progress
Commenced on oral metronidazole
Ongoing fluid balance problems
Dehydration due to diarrhoea
Worsening renal function
Fluid therapy resulting in pulmonary oedema
Prolonged HDU admission with other medical complications
Eventual resolution of diarrhoea & discharge 3 weeks later
13. C.difficile:Overview of clinical aspects
14. Overview
One of the most common healthcare-associated infections
Spectrum of disease ranging from asymptomatic carriage to fulminant colitis
Commonly a result of antibiotic therapy due to alteration of normal gut flora
15. Overview
Can occur without antibiotic use, importantly via nosocomial transmission
Mortality rates of up to~25% reported, particularly in elderly1
1. Crogan et al, GeriatrNurs 2007
16. Clinical aspects
17. Spectrum of disease
18. 1. Asymptomatic carriage
Approximately 20% of hospitalised patients are C. difficilecarriers
Significant reservoir for disease transmission
Contribution of hosts immune response is unclear
19. 2. C.difficilediarrhoea
Watery diarrhoea
>3 times per day
>2 days duration
More severe cases
Up to 15 motions per day
Lower abdominal pain and cramping
Low grade fever
Leucocytosis
Onset may be during antibiotic therapy or 5-10 days after treatment
Can present up to 10 weeks after antibiotic cessation
20. 3. C.difficile colitis
More significant illness than diarrhoea alone
Constitutional symptoms, fever, abdominal pain + watery diarrhoea
Colonoscopy:
Non-specific diffuse or patchy erythematous colitis
21. 22. 4. Pseudomembranous colitis
The classic manifestation of full-blown C.difficile colitis
Symptoms similar to, but often more severe than, colitis due to other causes
Unwell, WCC, hypoalbuminaemia
Colonoscopy:
Classical raised white/yellow plaques
23. 24. 5. Fulminant colitis
Severe manifestation affecting ~3%
Account for the most serious complications:
Perforation
Prolonged ileus
Toxic megacolon
Death
Clinical features of fever, leucocytosis, abdominal distension
25. 26. Extracolonic manifestations
Small bowel
Bacteraemia
Reactive arthritis
Others
27. 1. Small bowel
Particularly described in small bowel subjected to recent surgery
Inflammatory bowel disease post ileal-anal anastomosis
Pseudomembrane formation
May act as a reservoir for recurrent colonic infection?
28. 2. Bacteraemia
Uncommon
Associated with high mortality rate1
May be more common in patients with underlying gastrointestinal diseases2
Daruwala et al, Clin Med Case Reports 2009
Libby et al, Int J Infect Dis 2009
29. 3. Reactive arthritis
Polyarticular arthritis
Knee and wrist in 50% of cases
Onset average 11 days after diarrhoea1
Prolonged illness : average 68 days to resolve2
Birnbaum et al, ClinRheumatol 2008
Jacobs et al, Medicine (Baltimore) 2001
30. 4. Other extracolonic manifestations
Cellultis
Necrotisingfasciitis
Osteomyelitis
Prosthesis infection
Intra-abdominal abscess
Empyema
etc
31. Risk factors
32. Risk factors
General risk factors
Long duration antibiotics
Multiple antibiotics
Nature of faecal flora
Production of requisite cytotoxins
Presence of host risk factors
Specific risk factors
Immunosuppressive drugs
Gastric acid suppression
Cancer chemotherapy with antibiotic properties
33. Host risk factors
Advanced age
Nasogastric tube
Severe underlying illness
Prolonged hospitalisation
Enema therapy
GI stimulants
Stool softeners
34. Inflammatory bowel disease
Chronic, relapsing inflammatory disorders of the bowel of unknown aetiology
Ulcerative colitis
Crohns disease
Enteric infections account for ~10% of relapses
C.difficile in about half
May mimic a relapse, OR trigger a true relapse
35. Inflammatory bowel disease
Crucial that C.difficile is considered in the differential diagnosis of every flare
Otherwise inappropriate escalation of immunosuppression may result in severe infection
High index of suspicion required as classical pseudomembranes dont form in IBD
Treatment is to REDUCE their usual immunosuppressive drugs
36. Gastric acid suppression
37. Gastric acid suppression
Gastric acid inhibits germination of ingested C.dificile spores
Therefore, medications lowering gastric acid could increase risk of C.difficile infection
Clinical data are conflicting
38. 39. Imaging investigations
40. Imaging investigations
Abdominal xray
CT scan
Colonoscopy
41. Abdominal xray
Important in patients who are unwell with C.difficile infection
Findings:
Ileus
Toxic megacolon
Perforation
42. 43. CT scan
Diagnosis can often be made on CT alone
Several characteristic findings:
Gross bowel wall thickening
Luminal narrowing
Characteristic signs:
Accordion sign
Target sign
44. CT scan
45. 46. 47. Colonoscopy
Pathognomonic appearance of pseudomembranes
Raised, white/yellow plaques
Up to 1/3 right-sided only, so full colonoscopy better than sigmoidoscopy
Biopsies reveal spectrum of mucosal inflammation and necrosis
48. Colonoscopy
49. Colonoscopy
Beware colonoscopy in unwell patients with ileus or megacolon
Risk of perforation
If clinical picture and stool tests are suggestive, minimal role for colonoscopy
50. 51. Conclusion
Health-care associated infection of great clinical significance
Spectrum of disease ranging from asymptomatic infection to fuliminant colitis and death
Imaging investigations are complimentary to clinical index of suspicion
52. Recurrent C.difficile infection
Approximately 15-20% of patients with CDAD relapse following successful treatment
One relapse predicts further relapses!
Sudden recurrence of diarrhoea within ~1 week of treatment cessation