CDI Flashcards
Clostridioides difficile
Gram-positive
Anaerobic
Spore-forming, toxin producing
Colonizes intestinal tract (part of normal flora)
Pathogenesis
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
Mode of transmission
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
Clinical manifestations
In order of increasing severity:
1) Diarrhoea without colitis
2) Colitis
3) Severe colitis
4) Fulminant colitis
Clinical presentation - Diarrhoea without colitis
≥ 3 episodes of unformed stools in a 24h period
Clinical presentation - Colitis
1) Fever
2) Abdominal pain/cramps
3) Nausea
4) Anorexia
Clinical presentation - Severe coitis
1) Significant leukocytosis
2) Renal impairment
3) Sepsis
Clinical presentation - Fulminant colitis
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
Risk factors
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
Risk factor - Antibiotics
- Cause
- Will be at risk during
- Factors increasing risk
- How to reduce risk
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
Risk factor - PPI, H2RA
- Cause
- How to reduce risk
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
Diagnosis of CDI
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
Types of stool tests
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
What does each stool test detect
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
Stool tests used in clinical practice
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)
Diagnosis of CDI based on stool tests
Must have ≥ 2 positive stool tests out of the following:
1) GDH EIA
2) Toxin A & B EIA
3) NAAT
Repeat testing
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
Indication for stool tests
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
Infection control - Strategies
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
Infection control - When to implement infection control strategies
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
Need for antibiotic treatment algorithm
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
Classification of CDI - Initial VS Recurrent
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
Classification of CDI - Recurrent CDI
Any prior recurrence?
Yes: Subsequent recurrence
No: First recurrence
Classification of CDI - Initial CDI
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
Antibiotic treatment of initial episode (non-severe) - Choice of antibiotics
1st Line:
Vancomycin OR
Fidaxomicin
Alternative:
Metronidazole
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
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
Antibiotic treatment of initial episode (severe) - Dosing
Vancomycin
- PO 125 mg q6h
Fidaxomicin
- PO 200 mg q12h
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
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
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)
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
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
Antibiotic treatment of initial CDI - Duration
10 days
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
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
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
Types of adjunctive treatment
1) Probiotics
2) Anti-motility agents
- E.g. Loperamide, Diphenoxylate, Atropine
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
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
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
