IID 21: Therapeutics of C. difficile and Antibiotic Associated Diarrhea

What is diarrhea

Unusual passage of loose/watery stool at least 3 times in 24h

• type 6: fluffy pieces with ragged edges and mushy stool

• type 7: watery, no solid pieces, entirely liquid

Complications of diarrhea

• Dehydration

• Hypovolemia (critical reduction in circulating blood of fluid volume)

• Electrolyte disturbances

• Malabsorption of nutrients

Definition of a c diff infection present

• presence of diarrhea/megacolon w/o other known etiology AND lab confirmed presence of c diff

• diagnosis of typical pseudo-membrane on sigmoidoscopy/colonoscopy

• histological (study tissues under microscope) diagnosis of c diff w/ or w/o diarrhea

Definition of recurrent c diff infection

• resolution of symptoms following therapy, followed by reappearance of symptoms and pos c diff test withing 8 weeks

• more common in ppl w/ risk factors

How is c diff transmitted

• spores shed in feces

• contamination on surfaces (can last up to 5 months)

• ingestion of spores

Risk factors for c diff

• over 65yr, immunocompromised, history of inflammatory bowel disease, pt using antimicrobials, hospitalized, history of previous c diff

Pathophysiology of c diff inside host

• person ingests both spore and vegetative cells

• vegetative cell killed in stomach acid but spore remains

• spore germinate in small intestine when in contact w/ bile acid

• c diff multiplies in colon

• immunocompromised gut mucosa esp helps adherence to colonic epithelium

Pathophysiology of how c diff causes harm

• vegetative form releases 2 potent exotoxins → diarrhea + colitis

• toxin A: activates neutrophils to cause inflammation

• toxin B: more potent, cause colonic mucosal damage

Complications of c diff

• diarrhea

• pseudomembranous colitis

• toxin-induced ulcers on mucosal surface of intestine (raised yellow plaques)

• toxic megacolon

• prolong hospitalization

Mild to moderate c diff

WBC <= 15 × 10^9 per L and SCr < 133 umol/L (or < 1.5x increase from baseline)

Severe c diff

WBC >= 15 × 10^9 per L and SCr > 133 umol/L (or 1.5x increase from baseline)

Severe, complicated c diff

WBC >= 15 × 10^9 per L and SCr > 133 umol/L (or 1.5x increase from baseline)

AND

hypotension, shock, toxic megacolon

What is the 2 step testing algorithm for c diff

Treatment principles of c diff

• discontinue concomitant antimicrobials

• hydration

• correct electrolyte abnormalities

• discontinue laxatives

• tube feed in needed

• infection control measures

• monitor w/ stool chart

Antimicrobial treatment options for c diff

• metronidazole 500mg po/IV TID x 10 days

• vancomycin 125mg po QID x 10 days

• fidaxomicin 200mg po BID x 10 days

Monoclonal antibody treatment for c diff

• bezlotoxumab 10mg/kg IV x 1

  • human monoclonal antibodies that bind to toxin B and prevent it from entering GI: no colonic damage

  • not for ppl w/ history of heart issues

  • used in conjunction w/ antimicrobials

  • prevent recurrent c diff in high risk pts

Fecal microbiota transplant for c diff

• transfer of stool from healthy donor to a recipient w/ recurrent c diff to introduce healthy microbiota

• injected right into pt colon as a slurry, oral capsule, nasal tube into stomach into colon

• for pts with two or more recurrent episodes

• not for treatment, only for prevention of further reoccurrences

Which antimicrobial agent is better for what severity

• metro and vanco same for mild/moderate c diff

• vanco better than metro for severe c diff

• fidaxo and vanco same for curing c diff

• fidaxo resulted in lower rates of recurrence of c diff

Approach to treating initial episode of c diff

Approach to treating recurrent episode of c diff

Pt w/ 2 or more recurrences should be considered for FMT to prevent further recurrences

Are antidiarrheal agents recommended in c diff

• Can be used prn in pts with mild c diff being treated

• Avoided in untreated c diff and pt w/ severe c diff

Should PPIs be used in c diff

• increased risk of primary and recurrent c diff reported with gastric acid suppression (vegetative cells killed in acid)

Prevention measures for c diff

• no probiotics

• no prophylaxis therapy

• yes isolation precautions

  • full-barrier gown and gloves

  • spore resistant to hand sanitizers: must use soap/water

• yes antimicrobial stewardship

  • right drug at right dose for right duration

Antibiotic associated diarrhea vs c diff