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To reduce transmission within health care facilities, patients with suspected or proven C difficile infection should be placed on strict contact precautions and health care workers should apply careful handwashing before and after contact. If possible, therapy of the inciting antibiotic should be discontinued as soon as possible. The treatment of an initial episode of C difficile colitis is determined by the severity of disease. For patients with nonsevere disease, oral fidaxomicin (200 mg orally two times daily) and vancomycin (125 mg orally four times daily) are equally effective for initial treatment, but recurrence rates are lower with fidaxomicin than vancomycin (15% vs 25%). Fidaxomicin may be preferred as first-line treatment for patients believed to be at higher risk for recurrent disease. Recommended treatment duration is 10 days in most situations but is extended in patients requiring prolonged antibiotic therapy for other infections. Metronidazole (500 mg orally three times daily) is no longer recommended for initial therapy except when vancomycin or fidaxomicin is unavailable. Symptomatic improvement occurs in most patients within 72 hours. Following treatment, stool assays may remain positive for several weeks after symptom resolution.
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For patients with fulminant disease, vancomycin 500 mg orally four times daily along with metronidazole 500 mg intravenously every 8 hours are recommended. In patient with ileus, vancomycin may be administered by nasoenteric tube and by rectal enema (500 mg in 100 mL normal saline by enema every 6 hours). The efficacy of fidaxomicin for severe or fulminant disease requires further investigation. Early surgical consultation is recommended for all patients with severe or fulminant disease. Total abdominal colectomy or loop ileostomy with colonic lavage may be required in patients with toxic megacolon, perforation, sepsis, or hemorrhage.
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Bezlotoxumab is a monoclonal antibody to C difficile toxin B. It was approved by the FDA in 2016 for patients with C difficile infection who are receiving antimicrobial therapy with metronidazole, vancomycin, or fidaxomicin and are deemed at high risk for disease recurrence. In two phase III randomized controlled trials, patients given one intravenous infusion of bezlotoxumab had a lower risk of disease relapse within 12 weeks (16%) than patients given placebo (26%). In light of this modest clinical benefit, bezlotoxumab should be considered only in patients at high risk for disease recurrence, including patients who are immunocompromised, have inflammatory bowel disease, are undergoing dialysis, require continued antimicrobial therapy for ongoing infection, or have had prior C difficile recurrences.
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B. Treatment of Relapse
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Up to 20% of patients have a relapse of diarrhea from C difficile within 8 weeks after stopping initial therapy. This may be due to reinfection or failure to eradicate the organism. Current Infectious Disease Society of America guidelines recommend that the first recurrence be treated with fidaxomicin 200 mg orally twice daily for 10 days or with a prolonged tapering regimen of vancomycin 125 mg orally four times daily for 14 days; twice daily for 7 days; once daily for 7 days; then every other 2 or 3 days for 2–8 weeks. Second recurrence should be treated with an additional vancomycin tapering regimen, as above.
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For patients with three or more relapses, guidelines recommend consideration of fecal microbiota transplantation (FMT), in which a suspension of fecal bacteria from a healthy donor is given to the patient with infection. Fecal specimens that have been screened for infectious agents are commercially available. The fecal microbiota may be instilled into the patient by one of three methods: (1) infusion through a colonoscope into the terminal ileum and colon, (2) infusion through a nasoenteric tube into the duodenum, or (3) ingestion of multiple freeze-dried capsules. Due to its efficacy and relative safety and ease of administration, the oral capsule method has become the preferred mode of fecal administration in most patients. Using all three infusion modalities, multiple case series reported disease remission after a single treatment in over 90% of patients with recurrent C difficile infection. Furthermore, randomized studies have demonstrated significantly higher resolution of C difficile diarrhea with FMT (94%) than vancomycin (31%) and with FMT (92%) versus fidaxomicin (42%) or vancomycin (19%). However, FMT carries the potential risk of transmission of serious, even potentially fatal, infection. However, with proper screening and stool testing of donors, the risk of infections appears to be very low. In 2019, the FDA issued a safety alert regarding two cases of extended-spectrum beta-lactamase E coli infections in immunocompromised patients following FMT. In 2020, the FDA received reports of four patients developing STEC and two patients developing enteropathogenic E coli (EPEC) following FMT; four of the six patients required hospitalization. In addition, the manufacturer reported that two other patients had died following FMT from the STEC donor. Clinicians considering offering FMT must discuss with their patient this potential uncommon but very serious risk.
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