Last reviewed: 28 Sep 2021
Last updated: 17 Aug 2021
17 Aug 2021

IDSA/SHEA recommends fidaxomicin rather than vancomycin for treatment of initial and recurrent episodes

The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) have published new evidence-based guidelines on the management of Clostridium difficile infection.

This focused update of the previous guideline (published in 2018) includes three new updated recommendations on suggested treatments for patients with initial and recurrent episodes based on available new data.

IDSA/SHEA now recommends using fidaxomicin rather than a standard course of vancomycin for the treatment of an initial episode, based on moderate-certainty evidence. The recommendation places high value in the beneficial effects and safety of fidaxomicin, but acknowledges that its use depends upon resources as fidaxomicin is not widely available and is more costly compared to vancomycin. Vancomycin remains an acceptable alternative in these patients.

The guideline also now recommends using a standard or extended-pulsed regimen of fidaxomicin rather than a standard course of vancomycin for the treatment of a first recurrent episode, based on low-certainty evidence. Vancomycin in a tapered and pulsed regimen or as a standard course remains an acceptable alternative in these patients.

Finally, the guideline recommends that bezlotoxumab, a monoclonal antibody targeting toxin B produced by C difficile, may be used alongside standard of care antibiotics for the prevention of recurrence in patients who have had a recurrent episode in the last 6 months, particularly those who are at high risk of recurrence.

See Management: approach

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History and exam

Other diagnostic factors

  • fever
  • abdominal tenderness
  • nausea and vomiting
  • abdominal distension
  • symptoms of shock

Risk factors

  • antibiotic exposure
  • advanced age
  • hospitalization or residence in a nursing home
  • exposure to infected family member
  • history of Clostridium difficile-associated disease
  • use of acid-suppressing drugs
  • inflammatory bowel disease
  • solid organ transplant recipients
  • hematopoietic stem cell transplant recipients
  • chronic kidney disease
  • HIV infection
  • immunosuppressive agents or chemotherapy
  • gastrointestinal surgery
  • vitamin D deficiency

Diagnostic investigations

1st investigations to order

  • CBC
  • stool guaiac (fecal occult blood test)
  • stool polymerase chain reaction (PCR)
  • stool immunoassay for glutamate dehydrogenase
  • stool immunoassay for toxins A and B
  • abdominal x-ray

Investigations to consider

  • cell culture cytotoxicity neutralization assay
  • CT abdomen
  • sigmoidoscopy or colonoscopy

Emerging tests

  • stool lactoferrin or calprotectin

Treatment algorithm




Clinical Associate Professor of Medicine

Alabama Infectious Diseases Center




AH declares that he has no competing interests.

Peer reviewers

Julius Atashili, MD, MPH

Department of Epidemiology

Division of General Medicine and Epidemiology

UNC at Chapel Hill

Chapel Hill



JA declares that he has no competing interests.

Satish Keshav, MBBCh, DPhil, FRCP

Consultant Gastroenterologist

Department of Gastroenterology

John Radcliffe Hospital




SK declares that he has no competing interests.

Ian Beales, MD, FRCP

Clinical Reader and Consultant Gastroenterologist

Norfolk and Norwich University Hospital




IB declares that he has no competing interests.

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