What is the treatment for Clostridioides difficile (C. diff) infection?

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Last updated: April 25, 2025View editorial policy

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From the Guidelines

The most effective treatment for Clostridioides difficile (C. diff) infection is fidaxomicin 200 mg given twice daily for 10 days, as recommended by the 2021 focused update guidelines by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) 1. When considering treatment options, it's essential to assess the severity of the infection and the patient's medical history.

  • For an initial CDI episode, fidaxomicin is the preferred treatment, with vancomycin 125 mg given four times daily by mouth for 10 days as an alternative 1.
  • For first CDI recurrence, fidaxomicin or a tapered and pulsed vancomycin regimen is recommended, with adjunctive treatment using bezlotoxumab 10 mg/kg given intravenously once during administration of standard of care antibiotics, although caution is advised in patients with congestive heart failure 1.
  • For second or subsequent CDI recurrence, treatment options include fidaxomicin, vancomycin in a tapered and pulsed regimen, or vancomycin followed by rifaximin, with fecal microbiota transplantation considered after at least two recurrences 1.
  • For fulminant CDI, vancomycin 500 mg four times daily by mouth or by nasogastric tube, with or without rectal instillation, and intravenously administered metronidazole, is the recommended treatment 1. It's crucial to prioritize treatment strategies that minimize morbidity, mortality, and impact on quality of life, while also considering the availability of resources and potential risks associated with certain treatments, such as bezlotoxumab in patients with congestive heart failure 1.

From the FDA Drug Label

1 INDICATIONS AND USAGE 1.1 Clostridioides difficile-Associated Diarrhea DIFICID® is indicated in adult and pediatric patients aged 6 months and older for the treatment of C. difficile-associated diarrhea (CDAD).

C. diff treatment with fidaxomicin (PO) is indicated for adult and pediatric patients aged 6 months and older. The recommended dosage for adults is one 200 mg tablet orally twice daily for 10 days 2. For pediatric patients, the dosage varies based on weight, with tablets or oral suspension administered twice daily for 10 days 2. It is essential to complete the full course of therapy to reduce the development of drug-resistant bacteria and maintain the effectiveness of DIFICID and other antibacterial drugs 2.

From the Research

Treatment Options for C. difficile Infection

  • The primary treatment options for C. difficile infection include vancomycin, fidaxomicin, and fecal microbiota transplantation (FMT) 3, 4, 5, 6.
  • Vancomycin and fidaxomicin are recommended as the cornerstones for the treatment of C. difficile infection, with metronidazole only recommended for mild-to-moderate disease in younger patients with no or few risk factors for recurrence 4.
  • Fecal microbiota transplantation (FMT) is a reasonable treatment option with high cure rates in patients who have had multiple recurrent episodes and have received appropriate antibiotic therapy for at least three of the episodes 5, 6.

Comparison of Treatment Options

  • A study comparing fidaxomicin and vancomycin found that fidaxomicin was associated with a significantly lower rate of recurrence of C. difficile infection associated with non–North American Pulsed Field type 1 strains 3.
  • Another study found that FMT was superior to fidaxomicin and vancomycin for the treatment of recurrent C. difficile infection, with higher rates of clinical resolution and negative results from a polymerase chain reaction test for Clostridium difficile toxin 5.
  • A randomized trial comparing fidaxomicin with oral vancomycin for the treatment of C. difficile infection in hospitalized patients receiving concomitant antibiotics found similar rates of clinical cure and recurrence between the two groups 7.

Recurrent C. difficile Infection

  • Recurrent C. difficile infection is a significant problem, and treatment options include bezlotoxumab infusion, a monoclonal antibody against C. difficile toxin B, and FMT 4, 5.
  • FMT has been shown to be effective in treating recurrent C. difficile infection, with high cure rates and low rates of recurrence 5, 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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