Clostridioides Difficile Flashcards
What is Clostridioides difficile?
Gram-positive, spore forming anaerobic bacillus
What is the difference between toxigenic strains and non-toxigenic strains?
Toxigenic strains produce Toxin A and B capable of invading the tissues and causing inflammation + infection (Toxin B is 10-40x more potent)
Non-toxigenic strains do not producing toxins, can only colonize without causing infection
Toxigenic strains may not necessarily cause infections if they do not actively secrete toxins
Clostridioides difficile is the causative organism of ______ and _______________
CDAD (Clostridioides difficile associated diarrhea)
and
Pseudomembranous colitis
*It is the most common cause of nosocomial diarrhea
Clostridioides difficile are spores that are transmitted via ___________ route
List examples of how it might be transmitted
Fecal-oral route
- Transmitted via fomites
- Found in rooms of patient with CDI
- Found on hands of HCP
- Found on medical instruments
Presentation of Clostridioides difficile can range from ________ to __________
Asymptomatic carriage to Fulminant disease
May be asymptomatic due to:
- Non-toxigenic strain
- Toxigenic strain not actively producing toxins
- Host immune antibody production (against the toxins)
How is antibiotics involved in the pathogenesis of C. diff infection?
- Colonization of intestinal tract with C. diff occur via fecal-oral route
- Antibiotics disrupt the barrier function of normal colonic flora, creating a niche for C. diff to multiply and produce toxins
- Toxigenic C. diff strains release toxins
- Toxins cause mucosal damage, inflammation, and diarrhea
=> When toxins destroy the gut, YELLOW PLAQUES form over damaged epithelium, causing pseudomembranous colitis - Antibodies to the toxins can be protective. Asymptomatic carriers often have higher serum levels of antibodies.
What are the risk factors for C. diff?
- Advanced age >65yo
- Multiple or severe comorbidities
- Immunosuppression
- History of CDI
- GI surgery
- Tube feeding
- Prior hospitalization (last 1 year)
- Duration of hospitalization
- Residence in nursing home or long-term care facilities
- Use of antibiotics
- Use of gastric acid suppressive therapy (PPI)
All antibiotics are associated with CDI, esp those with gram-negative and anaerobic coverage (a/w the ecology of normal gut flora)
List the antibiotics with greatest risk of causing CDI. Also list those of medium risk.
Greatest risk:
- Clindamycin
- 3rd and 4th gen Cephalosporins
- Fluoroquinolones
Medium risk:
- Carbapenems
- 1st and 2nd gen Cephalosporins
- Beta lactam/BLI
CDI risk is highest when receiving antibiotics but still elevated up to _________
Still elevated up to 12 weeks later (gut flora not yet return to normal ecology)
Antibiotic stewardship is important because the risk of CDI increases with?
- Higher defined daily dose of Abx
- More Abx days (duration of exposure)
- More number of antibiotics used
*Impt to minimize FREQUENCY and DURATION of high-risk antibiotic therapy, as well as the NUMBER of Abx agents prescribed so as to reduce risk and hence incidence of CDI
Which antibiotic is preferred for use to prevent C. diff infection
(lowest risk of causing CDI)
Doxycyline/Tigecycline
- Active against C. difficile growth and inhibits toxin production
- Minimal effects on gut flora
List some CDI infection control and prevention measures
- Isolation
- Pt with CDI should be given private rooms w dedicated toilets to dcr transmission to other patients
- Prioritize pt with stool incontinence
- Hand hygiene
- Wear gloves and gowns
- Handwashing with soap and water to remove spores (alcohol handrub not effective)
- Environmental cleaning with sporicidal agents
- E.g., aldehyde, hydrogen peroxide, peracetic acid
- Antimicrobial stewardship
- Discontinue acid suppressive therapy
- Discontinue unnecessary PPIs
- Insufficient evidence but epidemiologic association poses a risk (may change the environment in GIT and colon)
- Probiotics
- Unknown benefit (right strain, dose, duration)
- But limited risk, may recommend
[1. Confirm presence of infection]
What is the cardinal symptom of CDI?
Cardinal symptom: Watery diarrhea (3 or more loose stools in 24h)
*Eliminate all other reason/cause for diarrhea
[1. Confirm presence of infection]
Describe the clinical presentation of mild CDI
Diarrhea, abdominal cramps
[1. Confirm presence of infection]
Describe the clinical presentation of moderate CDI
- Fever, malaise, nausea
- Diarrhea
- Abdominal cramps, distension
- Leukocytosis (elevated WBC)
- Hypovolemia
[1. Confirm presence of infection]
Describe the clinical presentation of severe CDI
*Much more systemic
- Fever
- Diarrhea
- Diffused abdominal cramps, distension
- WBC >= 15 x 10^9 /L
- SCr >= 133 umol/L (1.5mg/dL)
[1. Confirm presence of infection]
Describe the clinical presentation of fulminant CDI
- Hypotension/Shock
- Ileus (inhibit gut propulsion)
- Megacolon (enlarged, swelling colon)
[1. Confirm presence of infection]
What is required to diagnose CDI?
- Presence of diarrhea (3 or more unformed stool in 24h) OR radiographic evidence of ileus or toxic megacolon
AND
- A positive stool test result for C. diff or its toxin OR colonoscopic or histopathologic evidence of pseudomembranous colitis
*1 is related to presentation, 2 is related to diagnostic tests
[1. Confirm presence of infection]
CDI testing should only be performed in symptomatic patients because?
CDI laboratory testing cannot distinguish b/w colonization and infection
We do not want to treat asymptomatic colonization
- Waste infection control resources (such as private hospital rooms)
- Unnecessary treatment adds to antibiotic selection pressure and resistance
[1. Confirm presence of infection]
Are cultures taken for CDI diagnosing? Why or why not?
NO CULTURES (no stool, blood or urine culture)
- Due to long turnaround time
[1. Confirm presence of infection]
What stool tests (molecular/rapid diagnostic tests) are done for C. diff diagnosing? What are their respective pros and cons?
- Nucleic acid amplification test (NAAT)
- PROS: Identifies genes that produce toxin A and B
- CONS: Unable to differentiate if genes are activated or not
- Polymerase chain reaction (PCR)
- PROS: Identifies genes that produce toxin A and B
- CONS: Unable to differentiate if genes are activated or not
- Enzyme immunoassay (EIA) toxins A and B
- PROS: Identifies presence of toxin A and B
- CONS: low sensitivity, cannot be done alone
- Glutamate dehydrogenase (GDH) immunoassay
- PROS: Identifies all C. diff strains
- CONS: does not differentiate toxigenic strains
=> 1 and 2 can be done alone to confirm presence of infection, 3 and 4 must be done in combi
In which groups of patients should stool test for CDI be done?
- Only in symptomatic patients
- Testing is limited to pt with diarrhea (3 or more unformed stools per day)
- Only do after confirming that pt has not received a laxative within the prior 48h before sending test
Should stool test for CDI be repeated?
Do not repeat testing in <7 days
Do not repeat to document care
- Over 60% of patients with favourable clinical response continue to test positive for weeks
If patient is unable to discontinue additional antibiotic therapy when treating CDI, what should be considered?
- Select narrowest agent possible
- Avoid agents with a strong association with CDI (clindamycin, 3rd and 4th gen cephalosporins, fluoroquinolones)
- Consider a tetracycline if appropriate
[3. Antibiotic selection and regimen for INITIAL EPISODE]
What is defined as non-severe CDI?
WBC < 15 x 10^9 /L AND SCr < 133umol/L
[3. Antibiotic selection and regimen for INITIAL EPISODE]
How to treat non-severe CDI?
First line:
- PO Fidaxomicin 200mg BD
- PO Vancomycin 125mg QDS
Alternative:
- PO Metronidazole 400mg TDS (Sg has 200mg tablets, in guidelines it is 500mg TDS)
*Fidaxomicin has lower recurrence rate, but not available in Sg
[3. Antibiotic selection and regimen for INITIAL EPISODE]
How to determine the choice between Vancomycin and Metronidazole in non-severe CDI?
Vancomycin is preferred over Metronidazole if:
- Pt is more sick
- Pt has many comorbidities
- Low BP
- Frail elderly
- Experience lots of diarrhea
=> Assessed to be at higher risk of morbidity from C. diff
*Metronidazole considered in less sick presentation due to its lower success rate and higher recurrence rates
[3. Antibiotic selection and regimen for INITIAL EPISODE]
What is defined as severe CDI?
WBC >= 15 x 10^9 /L OR SCr >= 133umol/L
[3. Antibiotic selection and regimen for INITIAL EPISODE]
How to treat severe CDI?
First line:
- PO Fidaxomicin 200mg BD (not available in Sg)
- PO Vancomycin 125mg QDS
*Same as in non-severe
*Fidaxomicin has lower recurrence rate, but not available in Sg
[3. Antibiotic selection and regimen for INITIAL EPISODE]
What is defined as fulminant CDI?
Hypotension OR ileus OR megacolon
[3. Antibiotic selection and regimen for INITIAL EPISODE]
How to treat fulminant CDI?
First line:
IV Metronidazole 500mg q8h
+ PO Vancomycin 500mg QDS
+/- PR Vancomycin 500mg QDS
*PR: per rectum (via enema)
[3. Antibiotic selection and regimen for INITIAL EPISODE]
Why is IV metronidazole used in fulminant CDI?
Why can’t IV Vancomycin be used?
IV metronidazole undergoes enterohepatic circulation, and can concentrate in the gut
IV Vancomycin does not undergo enterohepatic circulation
PO Vancomycin has poor oral bioavailability, poor absorption allows it to accumulate in the colon
[3. Antibiotic selection and regimen for INITIAL EPISODE]
What is the treatment duration for initial episode of CDI?
10 days, may extend to 14 days if symptoms are not completely resolved
What is the definition of recurrent CDI?
Defined as resolution of CDI symptoms, followed by subsequent reappearance of symptoms after treatment has been discontinued
*around 30% of pt may experience recurrent CDI within 30 days of tx
What are the risk factors for recurrent CDI?
- Administration of other antibiotics during or after initial treatment of CDI
- Defective humoral immune response against C. diff toxins
- Advanced age
- Severe underlying disease
- Continued use of PPIs
[3. Antibiotic selection and regimen for FIRST RECURRENCE]
What would be the treatment and duration for first recurrence if patient had previously taken Fidaxomicin/Vancomycin for initial episode?
- PO Fidoxamicin 200mg BD x10 days
- PO Fidoxamicin 200mg BD x5 days, then 5mg EOD x20 days
- PO Vancomycin 125mg QDS 10-14 days, then 125mg BD x7 days, then 125mg daily x7 days, then 125mg every 2-3 days x2-8 weeks
*Tapered/pulse therapy
[3. Antibiotic selection and regimen for FIRST RECURRENCE]
What would be the treatment and duration for first recurrence if patient had previously taken Metronidazole for initial episode?
PO Vancomycin 125mg QDS x10 days
[4. Monitoring response]
What are the monitoring parameters for CDI treatment?
- Symptoms should resolve in 10 days, if not extend for another 4 days
- If poor response, perform additional diagnostics or consider escalation of pharmacologic treatment
- Do not continue C. diff treatment for concurrent antibiotics (no evidence of reduced recurrence for treatment longer than 10-14 days)
