C. difficile Diarrhea

Question 1

What are the risk factors for CDAD? (9)

Answer 1

1) Advanced age > 65 years

2) Multiple or severe comorbidities

3) Immuno suppression

4) History of CDI

5) GI surgery (affects ecology of GIT)

6) Tube feeding (may affect ecology of GIT)

7) Increased healthcare exposure (↑ risk of colonisation) e.g
- Prior hospitalization (last 1 year)
- ↑ Duration of hospitalization
- Residence in nursing home or long‐term care facilities

8) Use of antibiotics (e.g ↑ dose, days of treatment or number of antibiotics + differs between class used also; risk highest when receiving antibiotics but risk remains elevated up to 12 weeks after stopping)

9) Use of gastric acid suppressive therapy (e.g PPI; changes pH in colon and affect ecology)

Question 2

Which antibiotics haeve the greatest risk of causing CDAD?

Answer 2

1) Clindamycin (Odds Ratio 16.80)

2) Third‐ and fourth‐generation cephalosporins (OR 5.68)

3) Fluoroquinolones (OR 5.50)

usually those that have gram negative and anaerobe coverage -> more able to destroy the usual bacteria in the GIT; mostly broad spectrum except Clindamycin

Question 3

Which antibiotics may have protective effects against CDAD?

Answer 3

Doxycycline/ tigecycline

Question 4

What are the symptoms of fulminant CDAD?

Answer 4

1) Hypotension/shock

2) Ileus (cessation of gut motility with no sign of mechanical obstruction -> intolerant to oral intake)

3) Megacolon (very swollen colon)

4) Watery diarrhea (at least 3 loose stools within 24 hours)

Question 5

What are the symptoms of severe CDAD?

Answer 5

1) Fever, diffused abdominal cramps and distension

2) WBC ≥ 15 x 10^9/L or Scr ≥ 133 μmol/L (1.5 mg/dL)

3) Diarrhea

Question 6

What are the symptoms of moderate CDAD?

Answer 6

1) Fever, nausea, malaise

2) Abdominal cramps and distension

3) Leukocytosis (higher WBC)

4) Hypovolemia

5) Diarrhea

Question 7

What are the requirements of diagnosis of CDAD?

Answer 7

Presence of diarrhea (3 unformed stools in 24 hours not due to laxative or GI disease), OR Radiographic evidence of ileus or toxic megacolon

AND

A positive stool test result for C difficile or its toxins, OR Colonoscopic or histopathologic evidence of pseudomembranous colitis

Question 8

State what are the various stool tests, what they detect, and their limitations.

Answer 8

1) Nucleic acid amplification test (NAAT)
o Identifies genes that produces toxin A and B, does not differentiate if genes are activated and toxin is produced

2) Polymerase chain reaction (PCR)
o Identifies genes that produces toxin A and B, does not differentiate if genes are activated and toxin is produced

3) Enzyme immunoassay (EIA) toxins A and B
o But doesn’t pick it up very well so cannot be used as sole diagnostic yet

4) Glutamate dehydrogenase (GDH) immunoassay (least favoured)
o Identifies all forms of C. Diff but does not differentiate between non-toxic from toxic strains

Question 9

State the possible treatment regimen for this patient with first initial episode of CDAD.

[WBC < 15 x 10^9/L AND Scr < 133 μmol/L
(1.5 mg/dL)]

Answer 9

First Line:
- *PO Fidaxomicin 200mg BD
- PO Vancomycin 125mg QDS

Alternative:
- PO Metronidazole 400mg TDS

Duration: 10 days, may extend to 14 days if symptoms not completely resolved

Question 10

State the possible treatment regimen for this patient with first initial episode of CDAD.

[WBC ≥ 15 x 109/L OR Scr ≥ 133 μmol/L
(1.5 mg/dL)]

Answer 10

First Line:
- *PO Fidaxomicin 200mg BD
- PO Vancomycin 125mg QDS

Duration: 10-14 days

Question 11

State the possible treatment regimen for this patient with first initial episode of CDAD.

Symptoms: Hypotension OR ileus OR megacolon

Answer 11

IV Metronidazole 500mg Q8H + PO Vancomycin 500mg QDS +/- PR Vancomycin 500mg QDS

Duration: 10-14 days

Note: IV Metro can undergo enterohepatic circulation (EHC) so some still can get to GIT but IV Vanco cannot undergo EHC.

Question 12

What are the treatment principles of CDAD?

Answer 12

1) Do not treat asymptomatic patients with a positive C. difficile test
* Confirm symptoms consistent with CDI exist prior to prescribing therapy

2) If possible, discontinue any antibiotic therapy not specifically treating CDI

3) If additional antibiotic therapy is necessary:
* Select the narrowest agent possible
* Avoid agents with a strong association with CDI
* Consider a tetracycline if appropriate (protective effect)

Question 13

What are risk factors for recurrent CDAD? (4)

Answer 13

1) Administration of other antibiotics during or after initial treatment of CDI

2) A defective humoral immune response against C. difficile toxins

3) Advancing age and severe underlying disease (may have defective immune response also)

4) Continued use of PPIs

Question 14

State when stool test should/should not be conducted

Answer 14

SHOULD
- Confirm that patient has not received laxative within prior 48hr
- Only performed for symptomatic patients (asymptomatic colonisers don’t need treatment)

SHOULD NOT
- Repeat testing in < 7 days (CDAD will continue to be present for a few days)
- Repeat to document cure (most patients with favourable clinical responses continue to test positive)

Question 15

State the possible regimens for a patient with first recurrence of CDAD who was on Fidaxomicin/ Vancomycin for initial episode. (no need give the pulse dosing)

Answer 15

• PO Fidaxomicin 200mg BD x 10 days
• PO Fidaxomicin 200mg (pulsed)
• PO Vancomycin tapered/pulsed

Question 16

State the possible regimens for a patient with first recurrence of CDAD who was on Metronidazole for initial episode.

Answer 16

PO Vancomycin 125mg QDS for 10 days

Question 17

State how you would monitor a person with CDAD.

Answer 17

1) Symptoms should resolve in 10 days, if not, to extend another 4 days of treatment

2) Additional diagnostics or consider escalation pharmacologic treatment if poor response

3) Do not continue C. difficile treatment for concurrent antibiotics (if person still using other antibiotics after CDAD treatment ends, don’t continue CDAD treatment)
 No evidence of ↓ recurrence for treatment > 10‐14 days