FMT or Vancomycin as first line treatment for CDAD

Review by Prof. Eamonn Quigley (USA)

Study Summary 

Clostridioides difficile-related disease (CDAD) is a major public health issue which now affects not only hospitalized high-risk individuals but the general public as well. Increasing rates of resistance to metronidazole drive use of more expensive alternatives such as vancomycin and fidaxomicin. Meanwhile, fecal microbiota transfer/transplantation (FMT) has emerged as a highly effective therapy for those who fail or recur following antibiotics. Typically, FMT has been indicated after a third recurrence. If FMT is so effective why wait until recurrence occurs? This study randomized 104 individuals with a new episode of CDAD to either FMT (obtained from a national donor bank and delivered as an enema) and given once, or vancomycin 125 mg 4 times daily for 10 days. The primary end point (clinical cure and no recurrence within 60 days) was achieved in 66.7% of the FMT group and 61.2% of the vancomycin group. There were no differences between the groups in terms of adverse events.

Commentary 

As this trial adopted a non-inferiority approach, its conclusion, strictly speaking, is, therefore, that FMT is not inferior to vancomycin as a first-line treatment of CDAD. A number of points need to be emphasized. First, the donor material was derived from a nationally curated donor bank which ensured strict quality control, something that may not be possible everywhere and, if not optimal, could lead to serious infection-related adverse events. Second, the donor stool was administered via an enema, thereby avoiding the risk, expense, and accessibility issues that are associated with colonoscopy or the acceptability problems that accompany nasogastric or naso-enteral administration of FMT. If one can guarantee the highest standards of quality control, your regulatory authority approves, and payor reimburses, FMT delivered by enema can be considered as first-line therapy for C. difficile-related diarrhea.

Citation

Juul FE, Bretthauer M, Johnsen PH, Samy F, Tonby K, Berdal JE, Hoff DAL, Ofstad EH, Abraham A, Seip B, Wiig H, Rognstad ØB, Glad IF, Valeur J, Nissen-Lie AE, Ness-Jensen E, Lund KMA, Skjevling LK, Hanevik K, Skudal H, Melsom EJ, Boyar R, Cooper TJ, Ranheim TE, Riise EM, Adami HO, Kalager M, Løberg M, Garborg KK. Fecal Microbiota Transplantation Versus Vancomycin for Primary Clostridioides difficile Infection: A Randomized Controlled Trial. Ann Intern Med. 2025;178:940-947. 

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