2 - C. Dif Flashcards
Describe Toxin A
-Major pathogenic factor and has been characterized as an enterotoxin that causes intestinal fluid secretion, mucosal injury, and inflammation through actin disaggregation, intracellular calcium release, and damage to neurons.
Describe Toxin B
-Nonenterotoxic cytotoxin that causes depolymerization of filamentous actin and mediates more potent damage to human colonic mucosa than toxin A.
______ = enterotoxin
Toxin A
______ = cytotoxin
Toxin B
Which toxin is worse?
Toxin B
Is C. dif dose dependent?
No.
If an AB causes C. diff it needs to be removed, reducing dose of that agent will have no effect
ESBL
extended spectrum beta lactamases
Describe the bug of C. dif (characteristics)
- anaerobic
- GP
- spore-forming bacilli
C. dif colonizes ___% of hospitalized patients (fecal-oral transmission)
20-50
C. dif causes _____% of antimicrobial-associated diarrhea
10-20
C. dif causes _____% of antimicrobial-associated colitis
50-70
C. dif enterotoxin (A) and cytotoxin (B) cause ??
infection, inflammation, and colitis
C. dif has __% infection-related mortality
5
NAP1 strain is hyper-virulent strain of C. dif associated with hyper-production and _________-type toxin
C. perfringes
NAP1 strain associated with _______, first identified in Quebec where incidence increased from 36-156 cases per 100,000 between 1991 and 2003
outbreaks
Current estimates suggest _____% of CDI associated with NAP1
30-50
NAP1 is associated with higher rates of ?
- treatment failure
- 2x recurrence
- 2x complications
- 4x attributable mortality compared with non-NAP1
What is the main risk factor for CDI?
antimicrobial therapy
CDI
C. difficile infection
When does CDI typically result ?
within 4-9 days (up to 8 weeks) after AB therapy
Which antibiotics are at high risk of causing CDI?
- Cephalosporins
- Fluoroquinolones
- Penicillins
CFP
Which antibiotics are at moderate risk of causing CDI?
- Macrolides
- Sulfonamides
MS
Which antibiotics are at low risk of causing CDI?
- Aminoglycosides
- Tetracyclines
AT
List other risk factors for getting CDI (besides being on high-risk antibiotics)
- hospitalization > 72 hours
- elderly, debilitated, multiple co-morbidities, severe underlying disease, immunocompromised
- nasogastric tube, gastric acid suppression (antacids, H2 blockers, PPIs)
Why is gastric acid suppression a risk factor for C. dif?
PPI’s, antacids, & H2 blockers cause the pH to increase and therefore makes it a better environment for C. dif to grow
What are some clinical signs and symptoms of CDI?
- watery diarrhea with >3 unformed stools in 24 hours
- nausea, abdominal pain, high fever, very high leukocytosis
What are some complications that can arise from C. dif?
- septic shock
- pseudomembranous or fulminant colitis, ileus, toxic megacolon, perforation (may require colon removal)
How is CDI diagnosed?
- positive C. dif toxin in stool of symptomatic patient with diarrhea
- isolate culture and molecular typing during outbreaks
Does alcohol kill C. diff?
No - it is a spore.
List some important strategies for preventing CDI
- environmental cleaning and disinfection (C. dif is very infectious)
- healthcare worker hygiene and hand-washing (alcohol-based sanitizers not effective against spores)
- single rooms for patients with known CDI, contact/barrier precautions with gloves and gowns for patients with known or suspected CDI
- antimicrobial stewardship particularly for Clindamycin, FQs, and cephalosporins (high risk for C. dif)
Is the use of probiotics warranted for those with C. dif?
Data is inconsistent for the primary prevention of antimicrobial-associated diarrhea or CDI
Describe the approach for treating CDI
a) Discontinue offending antimicrobial, or replace with lower risk agent if needed
b) Supportive measures with hydration
c) avoid anti-motility agents (ex. loperamide, narcotics)
d) Surgery (loop ileostomy, colectomy) for severe, complicated disease
e) antimicrobial therapy for C. dif infection
Why do we want to avoid anti-motility agents (loperamide, narcotics) ?
need to get toxin out, don’t want to trap it in
What is the 1st line agent for mild-moderate CDI?
Include the duration
Metronidazole x 10-14 days
Why is Metronidazole the 1st line agent for mild-moderate CDI?
-preferred based on lower risk of collateral resistance and cost
Metronidazole has ____% response rate but lower 80% for NAP1 strains
90
____ will require a second treatment
1 in 5
Describe the response with metronidazole
IMPORTANT
typically afebrile within 2 days and diarrhea resolution within 5-7 days
Adverse effects of Metronidazole (list 4 besides GI)
- metallic taste (9%)
- disulifiram-reaction
- CNS (headache 18%, dizziness, confusion)
- peripheral neuropathy or neurotoxicity (potentially cumulative with multiple courses of therapy)
Is metronidazole expensive?
approx $20 for 10 day course
Besides metronidazole, what else can be used to treat mild-moderate C. diff? Include duration.
Vanco x 10-14 days
Why can’t you give Vanco IV for C. dif?
Bc you want it in the GI tract where the infection is.
Who is vancomycin preferred for in C. dif?
- pregnant or nursing women
- metro-intolerance
- metro treatment failure
- severe infection
Is Vanco less effective than metronidazole for C. dif?
No - at least as effective as Metro
What has fewer side effects:
Metro or Vanco
Vanco - since it is oral, vancomycin is not absorbed systemically and SE are not bad like metro
What is our concern with giving a patient Vanco?
collateral resistance, especially VRE
Is Vanco expensive?
Yes - capsules are $750
When is Vanco suggested?
If GI symptoms > 5 days, fever > 3 days, worsening or deteriorating during therapy
**If patient is on metro and still having diarrhea on day 5 of therapy, consider this a failure in treatment
Vanco or Metro:
What is better against NAP1?
Vanco
Severe infection associated with who/what?
- elderly, debilitated, inflammatory bowel disease, immunocompromised
- serum albumin < 30 g/L and WBC > 15, 000 or abdominal tenderness or SCR 1.5 x baseline
What would indicate a very severe infection?
- in critically ill with fulminant infection or septic shock
- ACG suggest ICU, hypotension, T > 38.5, ileum, confusion, WBC > 35,000 or <2000, organ failure)
Treatment for a very severe CDI?
Vanco 500mg + Metro 500mg
I assume x 10-14 days
Why is Vanco 500mg q6h instead of Vanco 125mg q6h ?
based on expert opinion only, consider 125mg for PO and 500mg for NG or PR
What would constitute recurrence?
Symptoms and positive C. difficile toxin within 8 weeks of initial episode.
___% chance of recurrence rate with multiple recurrences thereafter
25
For __________:
Consider probiotics such as Saccharomyces boulardii (500mg q12h), Lactobacilli rhamnosus GG, despite weak evidence for the secondary prevention of recurrent CDI
recurrence
What is the treatment for the 1st recurrence of CDI?
repeat initial therapy (50% response rate)
What is the treatment for > 2nd recurrence of CDI?
Vanco pulsing or tapering recommended in guidelines despite weak evidence
(ex. 125 mg q6h x 14 days, then q12h x 7d, q24h x 7d and q2-3d x 2-8 weeks
What is an alternative drug for recurrent CDI?
Fidaxomicin
What class if Fidaxomicin in?
macrocyclic antimicrobial
Fidaxomicin is ______ absorbed therefore well tolerated
poorly
When is Fidaxomicin used?
Used as last option for when multiple recurrence occurs
Is Fidaxomicin expensive?
Yes - $2200 for 10 days
FMT can also be done. What is this?
Fecal microbiota transplant - from healthy donor to alter and increase gut diversity
Describe how FMT is done
performed via nasogastric, nasojejunal, gastrostomy tube, colonoscopy or enema following antimicrobial therapy for C. dif infection
FMT has >___% response rate
80
Cons of FMT?
- lacks standardized products and procedures
- used for desperate patients
When are probiotics a risk?
Only in immunocompromised patients (introducing bacteria into their gut)
What are some other investigational options?
- monoclonal Toxin A and B antibodies
- C. difficile vaccine
What AB has HIGHEST risk of causing C. dif ?
Clindamycin
