Treatment of Recurrent C. difficile Infection

Introduction to Treatment Strategies

The Infectious Diseases Society of America recommends treating the first recurrence of C. difficile infection with oral vancomycin using a tapered and pulsed regimen, particularly if metronidazole was used for the initial episode 1, 2.
For second or subsequent recurrences, the treatment hierarchy includes fecal microbiota transplantation (FMT) as the most effective option, with strong recommendation and moderate quality evidence 1, 5.

The American College of Gastroenterology suggests that fidaxomicin 200 mg twice daily for 10 days is an excellent alternative for first recurrence, as it reduces subsequent recurrence rates compared to standard vancomycin (19.7% vs 35.5%, p=0.045) 2, 4.
The Infectious Diseases Society of America recommends against using metronidazole for recurrent CDI, as initial and sustained response rates are lower than vancomycin, and metronidazole carries risk of cumulative neurotoxicity with prolonged use 1, 2, 4.

Fecal microbiota transplantation (FMT) should be offered after at least 2 recurrences in patients who have failed appropriate antibiotic treatments, with strong recommendation and moderate quality evidence 1, 5, 4.
Vancomycin tapered and pulsed regimen remains an option for second or subsequent recurrences 1, 2, 4.

The Infectious Diseases Society of America suggests considering adding bezlotoxumab (monoclonal antibody against C. difficile toxin B) to standard antibiotic therapy for patients at high risk of recurrence, particularly for those with severe CDI presentation 4, 6.

The American College of Gastroenterology recommends discontinuing inciting antibiotics whenever possible, as continued antibiotic use is associated with treatment failure and increased recurrence risk 1, 2, 3.
The Infectious Diseases Society of America advises against using proton pump inhibitors if possible, as continued PPI use increases recurrence risk 1, 2.
Antimotility agents (loperamide, opiates) should not be used, as they can worsen outcomes 3.

The Infectious Diseases Society of America identifies risk factors that predict recurrence, including continued antibiotic use during or after CDI treatment, and severe initial disease 1, 2, 6.

For patients unable to take oral medications with recurrent CDI, intravenous metronidazole 500 mg every 8 hours PLUS vancomycin 500 mg via nasogastric tube four times daily and/or vancomycin 500 mg retention enema in 100 mL normal saline every 4-12 hours may be considered 3, 6, 7.
The American College of Gastroenterology notes that intravenous vancomycin has no efficacy against CDI, as it is not excreted into the colon 6.

The Infectious Diseases Society of America recommends obtaining prompt surgical evaluation if the patient develops perforation of the colon, toxic megacolon or severe ileus, serum lactate >5.0 mmol/L, or systemic inflammation with deteriorating clinical condition despite antibiotic therapy 7, 6, 3.