inpatient / gastroenterology

C Difficile Infection

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If You Remember Nothing Else

C Diff infectious symptoms are toxin-mediated and often only take hold when there is loss of usual gut microbiota. Thus, C Diff is commonly seen when patients are on broad-spectrum antibiotics in the hospital but up to 1/3 of new cases are community-acquired. C Diff testing should only be sent when the patient has >3 watery bowel movements in the last 24 hours. The severity should be determined based on WBC, creatinine, lactate, and vitals. You should pursue imaging if there is concern for complications including toxic megacolon, ileus, or microperforations. PO Vanc is the most commonly used treatment for initial cases. Consult ID for the treatment of recurrent disease, as the decision making can get complicated.
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Clinical Pearls

• C. Diff is gram pos bacillus and obligate anaerobe - only toxigenic strains cause infection
• Transmission is fecal-oral and is easily transmitted because spores are difficult to eradicate
• Pathogenesis requires the acquisition of C Diff plus loss of usual gut microbiota, often due to abx - commonly when on broad-spectrum antibiotics in the hospital, however about ⅓ of new cases are community-acquired 
• 20% of hospitalized patients are likely asymptomatic carriers
• Infectious symptoms of C Diff tend to arise 4-9 days into abx treatment
• The symptoms of C. Diff are toxin-mediated - toxin A is enterotoxic and toxin B is cytotoxic; Toxin A binds to the brush border of enterocytes and disrupts the actin cytoskeleton and leads to permeability and apoptosis causing diarrhea; Toxin B causes pore formation in the membrane leading to a cytopathic effect
• C. Diff studies should only be run if true diarrhea, as there will often be positive testing in colonized patients - that’s why labs will often refuse if the patient’s stool is formed; Only send when >3 watery bowel movements in last 24 hours
• Send GDH (glutamate dehydrogenase) assay and toxin assay - GDH sensitive for all C. Diff strains put can be pos without active infection, the toxin assay is specific for active disease but poorer sensitivity - in general, should see the positive toxin before treating; you should not restest within 7 days unless a significant change in diarrhea; can remain positive for 6 weeks even after adequately treated
• Endocsopy is usually not persued unless there is diagnostic uncertainty - pseudomembranes are usually only present in severe disease; Pseudomembranous colitis can be seen on imaging or endoscopy - formation of plaques that are essentially due to necrosis and exudation of fibrin - indicates an increased risk of adverse outcomes in patients with C Diff
• Secondary ppx with PO vanc 125-250mg BID may decrease recurrence in patients receiving systemic abx, but the literature is mixed
• Probiotics are not part of the guidelines, probably safe for patients to take, but should be used with caution in patients who are immunocompromised (risk and safety of probiotics) 
• Metronidazole is no longer the first line because of increased resistance
• IV vancomycin is not effective because it is insufficiency excreted into the colon
• Fidaxomicin is a bactericidal abx - better outcomes compared to vanc but expensive
• 25% of patients have recurrence after symptoms resolution - in such cases, a relapse is more common than a re-infection
• Imaging signs for complications - free air, loss of haustration, dilated small and large bowel without evidence of obstruction

Trials and Literature

• Cochrane Analysis for Treatment in C. Diff - essentially fidaxomicin > vanc > metronidazole, but the differences weren’t that big and fidaxomycin costs a lot more
• Meta-Analysis on Abx associated with C. Diff - the reason clinda gets all the hate when really many broad-spectrum abx can lead to C. Diff
• Fecal Microbiota transplant for C Diff - more effecting than vancomycin resolution of 81% vs 31% (small N) (NEJM, 2013)
• FMT is superior to fidaxomicin for recurrent C Diff - 71% vs 33% (Gastroenterology, 2019)
• Probiotics May Help Prevent C. Diff in those prescribed abx, NNT 25; however individual trials like PLACIDE do not show benefit
• MODIFY I and II Trials - actoxumab and bezlotoxumab (bind to toxins A and B, respectively) for prevention of recurrence of C Diff in 12 weeks after treatment - bezlotoxumab alone (17% vs 28%) and both together (16% vs 28%) reduced recurrence, but actoxumab alone did not 
• PEPTIC RCT - mortality same for PPI vs H2RA for ulcer ppx in intubated patients, they had essentially the same rate of C Diff infection as well

Other Resources

• C Diff Curbsiders Podcast - #117 Clostridium Difficile Infection