Lecture 31 CDiff infection Flashcards
What is C. difficile associated diarrhea (CDAD)?
normal GI flora disrupted ⇒ all antibacterials are implicated in this: fluoroquinolones, clindamycin, 3rd gen cephalosporins are particularly troublesome
this attaches to receptors in gut epithelial cell, proliferates and toxigenic strains may release toxins (Toxins A and B)
Toxin B is highly pathogenic essential for virulence
toxins cause inflammation and vasoconstriction leading to development of pseudomembranous colitis +/- necrosis
S&S: diarrhea, fever, ab pain, dehydration, etc
What are clinical manifestations of CDAD and complications, and risk fx?
onset 5-10 days after start of antibacterial tx but may occur as long as 10-12 weeks following
S&S: unformed stools, >/= 3 episodes in 24 hours may be brief and self-limited or cholera-like with >20 very liquid stools/day
blood in stools rare
fever 30-50%
leukocytosis 50-60% (>15 x 10^9/L)
ab pain or cramping 20-33%
Complications: dehydration, electrolyte disturbances, hypoalbuminemia, toxic megacolon, bowel perforation, hypotension, renal failure, sepsis/shock, death
Risk Fx: age >65, antimicrobial tx, hospitalization, cancer chemotherapy, severe underlying illness, manipulation of GI tract
How is CDAD diagnosed?
diarrhea - >/= 3 unformed stools in </= 24 hours AND >/= 1 of: positive stool test for C. diff or its toxins OR evidence of pseudomembranous colitis ⇒ this criteria is used for diagnosing initial and recurrent episodes (unless paralytic ileus present)
Stool culture (72 hours) - GOLD STANDARD (not practical to use routinely)
NAATs like PCR to detect toxin genes the preferred test
ow should CDAD tx for patients be approached?
discontinue all unnecessary antimicrobials and avoid antiperistaltics, determine if its an initial or recurrent episode
if severe tx should include: IV fluid and electrolyte resuscitation, VTE prophylaxis, oral or enteral feeding should be continued unless pt has paralytic ileus, use of probiotics not currently recommended
What are the criteria for initial and recurrent episodes of CDAD?
Initial: sx of CDAD, NO positive C. diff test results in the last 8 weeks
Recurrent: up to 25% of treated CDAD pt have a recurrence, recurrences may be due to relapse with original strain or re-infection with new strain
⇒ sx of CDAD, >/= 1 positive C. diff test result in last 8 weeks
How is an initial or 1st recurrence of a CDAD episode classified by severity?
Mild-Moderate: leukocytosis (WBC <15 x 10^9/L) AND SCr < 130
Severe: leukocytosis (WBC >15 x 10^9/L) OR SCr >/= 130
Severe, complicated (fulminant): hypotension, shock, ileus, and/or megacolon
What are therapeutic options for CDAD (absorption, collateral, AE)?
Metronidazole: >/= 85% absorption following oral dose
affects other gut bacteria
AE: peripheral neuropathy, darkened urine, others
Vancomycin: negligible absorption following oral dose, affects some gut bacteria
AE: minimal systemic
Fidaxomicin: minimal absorption following oral dose, limited activity against other gut bacteria - also preserves Bacteroides groups in fecal flora
AE: minimal systemic
What are tx recommendations for initial episodes of CDAD?
Mild-Moderate: Vancomycin 125 mg PO QID F10D OR Fidaxomicin 200 mg PO BID F10D OR if above two not available ⇒ metronidazole 500 mg PO TID F10D
Severe, uncomplicated: Vancomycin 125 mg PO QID F10D OR Fidaxomicin 200 mg PO BID F10D
Severe, complicated (fulminant): Vancomycin 500 mg PO/NG QID F10-14D AND Metronidazole 500 mg IV Q8H
What are tx recommendations for recurrent episodes of CDAD?
First One: Vancomycin 125 mg PO QID F10D if metronidazole was used for initial episode OR prolonged tapered and pulsed vancomycin if a standard regimen was used initially (ex. 125 mg PO QID F10-14D then BID F7D then QD F7D then Q2-3D F2-8W OR Fidaxomicin 200 mg PO BID F10D if vancomycin was used initially
Second or Subsequent: vancomycin in tapered and pulsed regimen OR vancomycin 125 mg PO QID F10D followed by Rifaximin 400 mg PO TID F20D OR Fidaxomicin 200 mg PO BID F10D OR fecal microbiota transplantation
What is bezlotoxumab?
monoclonal antibody against C. diff toxin B,, addition to antibacterials may reduce recurrence of CDI
2 RCTs found sustained cure through 12 weeks: 64% vs 54%
