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CDI Flashcards

1
Q

Clostridioides difficile

A

Gram-positive
Anaerobic
Spore-forming, toxin producing
Colonizes intestinal tract (part of normal flora)

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2
Q

Pathogenesis

A

Normal gut flora altered due to use of broad spectrum antibiotics
- Broad spectrum antibiotics able to clear other normal gut flora but don’t cover C. difficile –> decrease competition –> allow C. difficile to proliferate & become active
C. difficile contain endospores
- Spores are normally dormant but can germinate to form vegetative cells that initiate CDI
C. difficile can survive acidity of stomach and reach large intestines –> flourishes within the colon
C. difficile produces toxins A & B –> can cause inflammation & mucosal cell death
Pseudomembranous colitis
- Occurs with untreated/uncontrolled CDI
- Indication of severe CDI

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3
Q

Mode of transmission

A

Fecal-to-oral

  • E.g. Touch surfaces contaminated with feces from infected person
  • E.g. Lack of handwashing with soap and water can increase transmission
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4
Q

Clinical manifestations

A

In order of increasing severity:

1) Diarrhoea without colitis
2) Colitis
3) Severe colitis
4) Fulminant colitis

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5
Q

Clinical presentation - Diarrhoea without colitis

A

≥ 3 episodes of unformed stools in a 24h period

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6
Q

Clinical presentation - Colitis

A

1) Fever
2) Abdominal pain/cramps
3) Nausea
4) Anorexia

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7
Q

Clinical presentation - Severe coitis

A

1) Significant leukocytosis
2) Renal impairment
3) Sepsis

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8
Q

Clinical presentation - Fulminant colitis

A

Complications:

1) Toxic megacolon
- Intestines lose ability to contract & become dilated
- Can result in buildup of toxins & C. difficile –> perforation

2) Pseudomembranous colitis
- Yellowish plaques form over damaged intestinal epithelium

3) Ileus
- Intestinal paralysis (gut is not moving)

4) Colonic perforation
- Toxins cause inflammation of gut mucosa –> perforation

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9
Q

Risk factors

A

Pharmacotherapy

1) Antibiotics
2) PPI, Histamine type 2 blockers

Healthcare exposure

1) Current hospitalization
- CDI is a common nosocomial infection
- May be exposed via to contaminated environment / hands of HCP (transiently contaminated with C. difficile spores
- Hospitalized patients may be on antibiotics –> increased risk of developing CDI
2) Prior hospitalization
3) Duration of hospitalization
4) Long-term care residency

Age

1) ≥ 65 years
2) Per year increment over 18 years

Host immunity

1) Lack of antibody response to C. difficile toxin
- E.g. Due to immunosuppression (transplant, chemotherapy)
2) Severe underlying illness
3) Comorbidities e.g. DM, stroke, heart disease
- Visit healthcare institutes more frequently –> increased risk of transmission
- Impaired physiology

CDI experience
1) Past CDI

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10
Q

Risk factor - Antibiotics

  • Cause
  • Will be at risk during
  • Factors increasing risk
  • How to reduce risk
A

Cause:
1) Due to ability of antibiotics to suppress normal bowel microbiota (but doesn’t cover C. difficile)

Will be at risk during:

1) Antibiotic therapy
2) Up to 1 month post exposure

Factors increasing risk:

1) Increased exposure of systemic antibiotics
- E.g. Increased no., duration, dose
2) Use of high-risk antibiotics:
- Clindamycin
- 3rd-4th generation Cephalosporins
- Amoxicillin, Ampicillin
- Fluoroquinolones

Note: All routes will have risk

  • Can distribute to the GIT
  • Topical antibiotics may have lower risk, but generally will have risk as long as there is systemic absorption

How to reduce risk:

1) Antimicrobial stewardship
- Minimize exposure (frequency, duration, no.) of antibiotics

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11
Q

Risk factor - PPI, H2RA

  • Cause
  • How to reduce risk
A

Cause:
1) Decrease gastric acid –> allow ingested C. difficile to survive

How to reduce risk:

1) Discontinue unnecessary PPIs
- Note: Do not discontinue if indicated

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12
Q

Diagnosis of CDI

A

Laboratory testing alone is unable to distinguish between asymptomatic colonization & clinical symptoms of infection

Diagnostic criteria:
Unexplained new onset diarrhoea 
- ≥ 3 episodes of unformed stools in 24h
OR 
Radiologic evidence of ileus / toxic megacolon

AND

Positive stool test for presence of toxigenic C. difficile & its toxins
OR
Histopathologic findings of pseudomembranous colitis

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13
Q

Types of stool tests

A

1) Toxigenic culture
2) Cell culture cytotoxicity neutralization assay
3) Glutamate dehydrogenase (GDH) EIA
4) Toxin A & B EIA
4) Nucleic acid amplification tests (NAAT)
- PCR commonly used

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14
Q

What does each stool test detect

A

Toxigenic culture
- Detects C. difficile spores/cells

Cell culture cytotoxicity neutralization assay
- Detects Toxins A & B (free toxins)

GDH EIA

  • Detects C. difficile common antigen (i.e. presence of C. difficile)
  • Limitation: Unable to determine if C. difficile detected is toxin-producing (only toxin-producing causes CDI)

Toxin A & B EIA

  • Detects Toxins A or B (free toxins)
  • Limitation: Unable to detect whether C. difficile is present

NAAT

  • Detects C. difficile toxigenic gene (i.e. presence of toxin-producing C. difficile)
  • Limitation: Unable to differentiate between colonization VS true infection
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15
Q

Stool tests used in clinical practice

A

1) GDH EIA
2) Toxin A & B EIA
3) NAAT

Toxigenic culture & cell culture cytotoxicity neutralization assay NOT used due to long turnaround time (24 - 48h)

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16
Q

Diagnosis of CDI based on stool tests

A

Must have ≥ 2 positive stool tests out of the following:

1) GDH EIA
2) Toxin A & B EIA
3) NAAT

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17
Q

Repeat testing

A

NOT recommended within 2 weeks of previous positive test

- Likely to have colonization –> test will come back positive –> won’t help with treatment and managing patient

18
Q

Indication for stool tests

A

When suspect CDI:
- Carry out GDH EIA + Toxin A & B EIA

NAAT only carried out when:

1) Unsure of cause of diarrhoea
- Will carry out series of tests (GI panel) (including NAAT) –> test for presence of possible pathogens
2) Only 1 positive test result after carrying out GDH EIA + Toxin A & B EIA
- Need at least 2 positive test results to make diagnosis

19
Q

Infection control - Strategies

A

1) Rapidly identify & isolate infected patients
- Liquid stools –> easy to spread to patients in same ward (shared toilets)
2) Appropriate PPE when caring for infected patients
- Gowns & gloves
3) Good hand hygiene before & after contact with patients
- Alcohol handrub is insufficient to kill spore-forming bacteria –> must wash with water & soap
4) Environmental management
- Reusable equipment and surfaces of room CDI patient was treated in should be cleansed/treated with EDA-approved, sporicidal disinfectant

20
Q

Infection control - When to implement infection control strategies

A

Implement for all suspected cases (not just confirmed cases)

Can take out of isolation once:

1) Rule out CDI
2) Patient is diarrhoea-free for at least 48h

21
Q

Need for antibiotic treatment algorithm

A

1) Symptoms of CDI present?
- Yes: Suspect CDI
- No: No need to treat/test

2) Suspect CDI
- Stool testing
- Stop precipitating antibiotics (if possible) / Switch to narrower spectrum antibiotic
- Stop drugs that can cause diarrhoea (if possible)
- Initiate infection control strategies

3) ≥ 2 Positive stool tests?
- Yes: Initate antibiotics
- No: No need to treat. Cause of diarrhoea unlikely to be CDI

22
Q

Classification of CDI - Initial VS Recurrent

A

At time of symptom onset, time of last positive test result:
1) > 8 weeks ago: Initial episode

2) Within 2-8 weeks ago: Recurrent episode

3) < 2 weeks ago: Continue/Complete previous CDI treatment
- I.e. Considered same infection as previous CDI
- This case is rarely seen since repeat testing within 2 weeks of previous positive test is not recommended

23
Q

Classification of CDI - Recurrent CDI

A

Any prior recurrence?
Yes: Subsequent recurrence
No: First recurrence

24
Q

Classification of CDI - Initial CDI

A

1) Severe symptoms present?
- Severe symptoms (any one): WBC ≥ 15 x 10^9 / L OR SCr ≥ 1.5 mg/dL (133 mmol/L)
- Present: Complications present?
- Not present: Non-severe CDI

2) Complications present?
- Complications: (1) Toxic megacolon (2) Pseudomembranous colitis (3) Ileus (4) Colonic perforation
- Present: Fulminant colitis
- Not present: Severe colitis

25
Antibiotic treatment of initial episode (non-severe) - Choice of antibiotics
1st Line: Vancomycin OR Fidaxomicin Alternative: Metronidazole
26
Antibiotic treatment of initial episode (non-severe) - Dosing
Vancomycin - PO 125 mg q6h Fidaxomicin - PO 200 mg q12h Metronidazole - PO 400 mg q8h - Guidelines recommend PO 500mg q8h but SG only has 200 mg tabs
27
Antibiotic treatment of initial episode (severe) - Choice of antibiotics
1st Line: Vancomycin OR Fidaxomicin PO Metronidazole NOT used - New data suggesting higher treatment failure rates in severe/complicated CDI
28
Antibiotic treatment of initial episode (severe) - Dosing
Vancomycin - PO 125 mg q6h Fidaxomicin - PO 200 mg q12h
29
Antibiotic treatment of initial episode (fulminant) - Choice of antibiotics
1st Line: Vancomycin - IV Metronidazole may be considered if Vancomycin is C/I (but lower efficacy) If ileus present, add on: IV Metronidazole AND PR Vancomycin - Concerns over impaired ability for PO Vancomycin to reach entire colon since gut is not moving - PR Vancomycin able to cover lower bowels
30
Antibiotic treatment of initial episode (fulminant) - Dosing
Vancomycin - PO 500 mg q6h - PR 500 mg in 100mL NS q6h (rectal instillation via enema) Metronidazole - IV 500 mg q8h
31
Treatment considerations - Vancomycin - Clinical use - Route - Alternatives if Vancomycin is C/I
Clinical use: 1st line for initial CDI (regardless of severity) Route: Avoid IV Vancomycin - Distributes to other tissues --> GIT concentrations insufficient to treat CDI - VS PO Vancomycin --> poor systemic absorption --> concentrates in GIT Alternatives if Vancomycin is C/I: Non-severe CDI: - PO Metronidazole / PO Fidaxomicin Severe CDI - Must do literature search/look at case reports to see what works - May consider Fidaxomicin / older agents Fulminant CDI - May consider IV Metronidazole (but lower efficacy)
32
Treatment considerations - Metronidazole | - Clinical use
PO Metronidazole formerly 1st line for non-severe CDI Now: - Alternative in non-severe CDI - PO Metronidazole NOT used severe / fulminant CDI Due to new data suggesting higher treatment failure rates in severe / fulminant CDI
33
Treatment considerations - Fidaxomicin - Advantages - Limitations
Advantages: 1) Narrower spectrum 2) Lower MIC against C. difficile 3) Prolonged post antibiotic effect - Lower frequency 4) Bactericidal --> more effective - VS Vancomycin --> bacteriostatic 5) Higher rates of symptomatic cure (VS Vancomycin) 6) Associated with lower rates of CDI recurrence (VS Vancomycin) Disadvantages: 1) Not registered in SG; Not stocked in hospital formularies - Only brought in on a case-by-case basis 2) Very costly 3) Limited data to support use in fulminant CDI
34
Antibiotic treatment of initial CDI - Duration
10 days
35
Administration of PO Vancomycin
Not available as oral dosage form Must reconstitute from Vancomycin injection vials (1 vial = 500 mg Vancomycin) Reconstitute with normal saline / water for injection / 5% dextrose Use oral syringe to draw out dose
36
Antibiotic treatment of recurrent CDI - First recurrence
Initial antibiotic: Vancomycin 1) Prolonged tapered/pulsed Vancomycin regimen - PO Vancomycin 125 mg q6h x 10 - 14 days; then - PO Vancomycin 125 mg q12h x 7 days; then - PO Vancomycin 125 mg q24h x 7 days; then - PO Vancomycin 125 mg every 2 - 3 days x 2 - 8 weeks OR 2) Fidoxamicin PO 200 mg q12h x 10 days Initial antibiotic: Metronidazole 1) Vancomycin PO 125 mg q6h x 10 days Initial antibiotic: Fidoxamicin 1) Prolonged tapered/pulsed Vancomycin regimen - PO Vancomycin 125 mg q6h x 10 - 14 days; then - PO Vancomycin 125 mg q12h x 7 days; then - PO Vancomycin 125 mg q24h x 7 days; then - PO Vancomycin 125 mg every 2 - 3 days x 2 - 8 weeks
37
Antibiotic treatment of recurrent CDI - Subsequent recurrence
1) Prolonged tapered/pulsed Vancomycin regimen - PO Vancomycin 125 mg q6h x 10 - 14 days; then - PO Vancomycin 125 mg q12h x 7 days; then - PO Vancomycin 125 mg q24h x 7 days; then - PO Vancomycin 125 mg every 2 - 3 days x 2 - 8 weeks OR 2) Vancomycin PO 125 mg q6h x 10 days; then Rifaximin PO 400 mg q8h x 20 days OR 3) Fidaxomicin PO 200 mg q12h x 10 days OR 4) Fecal microbiota transplantation (FMT) - If failed appropriate antibiotic treatment for at least 2 recurrences - Instillation of healthy donor stools into GIT of patient with recurrent CDI --> restore gut microbiota diversity
38
Types of adjunctive treatment
1) Probiotics 2) Anti-motility agents - E.g. Loperamide, Diphenoxylate, Atropine
39
Probiotics - Benefits - Limitations - Recommendation
Benefits: 1) Restore normal gut microbiota 2) Generally safe & well-tolerated Limitations: 1) Insufficient data to provide recommendation on its use 2) Role in treatment & prevention of CDI & infectious diarrhoea is unclear 3) Unclear if will remain active once exposed to antibiotic treatment 4) Additional pill burden & cost, especially with evidence of benefits Recommendation 1) NOT recommended as adjunctive treatment to antibiotics 2) May be considered in self-limiting diarrhoea - May help with resolution of symptoms
40
Anti-motility agents - Benefits - Limitations - Recommendation
Benefits: 1) Inhibit contraction of intestinal smooth muscles --> symptomatic relief Limitations 1) Limited role in infectious diarrhoea (especially inflammatory diarrhoea & CDI) 2) Reduce bowel output --> affect ability to carry out stool testing - Delay diagnosis & treatment 3) Mask fluid loss - May under-hydrate patients 4) Associated with poor outcomes, especially if diarrhoea is not treated appropriately Recommendation: 1) NOT recommended
41
Monitoring
Clinical improvement 1) Resolution/Improvement of symptoms within a few days of initiating treatment - Improvement in diarrhoea frequency & consistency, leukocytosis 2) Near complete resolution expected within 10 days of treatment 3) Repeat stool testing NOT recommended to assess cure - Will likely test positive due to colonization

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