Module 2: C. Diff Flashcards
Describe the pathogenesis of c. diff.
antibiotic therapy
- disruption of colonic microflora
- c. difficile exposure and colonization
- release of toxin A (“enterotoxin”) and toxin B (“cytotoxin”)
- Mucosal injury and inflammation
How is c. diff diagnosed?
Stool + for toxigenic Clostridioides difficile and it’s toxins or
Colonscopic or histopatholgic findings of pseudomembranous colitis
Major risk factors for c.diff = tx with abx, PPI’s, or antineoplastic agents within previous 8 weeks
What are the three general principles of CDI management?
Antibiotic management - d/c ASAP or switch to abx with lower CDI SE
Infection control - contact precautions and educate family
Nutrition and fluid management -
What is fulminant CDI?
previously known as severe, complicated CDI
may be characterized by hypotension or shock, ileus (obstruction) or megacolon (colon abnormally dilated).
What is the recommended treatment for initial nonsevere, non-fulminant CDI?
Fidaxomicin - 200mg BID PO x 10 days
Vanco - 125mg QD PO x 10 days
Metronidazole - 500 mg TID x 10-14 days
Fidax favoured for decreased recurrence rates.
Metronidazole assoc with treatment failure.
When should metronidazole be avoided?
patients with severe disease, patients who are frail, elderly or have multiple medical conditions and in patients who develop CDI in association with IBD.
When should a surgical consult for CDI be indicated?
In fulminant CID with poor prognosis:
* Hypotension
* Fever ≥38.5°C
* Ileus or significant abdominal distension
* Peritonitis or significant abdominal tenderness
* Altered mental status
* White blood cell count ≥20,000 cells/mL
* Serum lactate level >2.2 mmol/L
* Admission to intensive care unit
* End organ failure (eg, requiring mechanical ventilation, kidney failure)
* Failure to improve after 3 to 5 days of maximal medical therapy
If patient requires long term abx and is positive for CDI what is the treatment course?
Continue to receive CDI tx throughout antibiotic course and additional period of 1 week or 14 days with metronidazole.
What is recurrent CDI?
Resolution of CDI symptoms while on appropriate therapy followed by reappearance of symptoms within 2-8 weeks after tx has stopped.
What is the tx regiman for first recurrence of nonsevere, non-fulminant CDI
Prior tx with vanco:
- Fidax 200mg BID x 10 days OR fidax 200mg BID x 5 days follow by every other day for 20 days
Prior tx with fidax:
- vanco pulse-tapered fashion OR vanco 125mg po QD x 10 days
With prior CDI in last 6 months - adjunctive use of bezlotoxumab
NOTE: pulse-tapered vanco =
125mg po QD x10-14 days
125mg po BID x 7 days
125mg po OD x 7 days
125mg po OD every 2-3 days for 2-8 weeks
What is the tx for second or more recurrance of nonsevere, non-fulminant CDI?
- Fidax 200mg BID x 10 days OR fidax 200mg BID x 5 days follow by every other day for 20 days
- vanco pulse-tapered fashion OR vanco 125mg po QD x 10 days
Live biotherapeutic product (e.g. rectal suspension, oral capsule) after completion of CDI therapy or one time dose of bezlotoxumab dose during therapy.
When would a fecal microbiota transplantation be indicated and what are the cautions?
3 or more episodes of CDI
Risk of colonic perforation so should be performed by personnel with appropriate expertise.
What is the tx for severe or fulminant CDI?
Antibiotic therapy 10-14 days:
- Vanco 500 mg PO QD AND
- Metronidazole IV 500 mg q8h
FMT: where available
Surgical consult
What medications should be avoided in CDI?
Antimotility agents = slowing down can worsen infection potentially leading to complications like megacolon
Probiotics = pose a risk of bacteremia/ fungemia in immunocompromised patients
What is the drug formulary for fidax, vanco and metronidazole.
Fidax - partial coverage, special authority required. Most expensive to patient.
Vanco - partial coverage, special authority required
Metronidazole - partial coverage. Cheapest for patient.
Is fidaxomicin safe in pregnancy and breastfeeding?
Limited systemic absorption may limit potential fetal exposure and distribution into breast milk
What are common adverse reactions to fidaxomicin?
Nausea
Pruiritus
Contraindications for fidaxomicin?
macrolide allergy
What is the difference between nonsevere non-fulminant CDI, severe non-fulminant CDI and fulminant colitis?
nonsevere, non-fulminant CDI = WBC <15,000 cells/microL and serum creatinine <1.5 mg/dL
Severe non-fulminant CDI = WBC >15,000 and/or serum creatinine >1.5 mg/dL
Fulminant colitis = presence of hypotension or shock, ileus, megacolon or C. diff bacteremia.
Why is vanco cautioned in IBD?
Increased serum concentrations found in patients with IBD treated with vanco for C. Diff. Monitor for adverse reactions to vanco and serum concentrations in patients with renal insufficiency, severe colitis and a prolonged course.
Why is vanco cautioned in patients with renal impairment?
Has been associated with nephrotoxicity especially if taken with other nephrotoxic drugs. Dosage modification and close monitoring required in existing or high risk renal impairment. Monitor serum concentrations of vanco.
Which populations should be cautioned in using metronidazole?
Hepatic and renal impairment (can cause accumulation). Seizure disorder. Polypharmacy - significant drug interactions exist.
What are cautions with bezlotoxumab?
Heart failure observed in patients with underlying cardiac conditions. Should only be used when benefits outweigh risks.
Is vanco recommended in pregnancy and lactation?
Yes - recommended in pregnancy for treatment of c. diff.
Oral absorption is minimal so presence in breast milk is limited.
