Fecal microbiota transplantation may be more effective than vancomycin in treating primary C. difficile infection

1. In this randomized controlled trial, a higher proportion of patients who underwent fecal microbiota transplantation achieved clinical cure of primary Clostridioides difficile infection without recurrence compared with patients who were treated with vancomycin.

2. The frequency of adverse events was similar between the two groups, and no adverse events were deemed to be related to the study treatment.

Evidence Rating Level: 1 (Excellent)

Study Rundown: The current recommended treatment for primary Clostridioides difficile infection (CDI) involves the antibiotics vancomycin or fidaxomicin. However, with 10-20% of patients experience symptom recurrence following treatment, repeated antibiotic regimens are often required, resulting in further cost, adverse effects, and patient burden as well as promoting antibiotic resistance. Fecal microbiota transplantation (FMT) has been promoted as a treatment for recurrent CDI that reduces antibiotic use; however, recent studies have suggested that it may be effective for primary CDI as well. This prospective non-inferiority study aimed to directly compare FMT with vancomycin in treating primary CDI. It was found that, while the vancomycin group initially had a numerically greater percentage of patients who achieved clinical cure at the two-week time point compared to the FMT group, the FMT group had fewer patients with recurrence within sixty days. Subgroup analysis showed consistent results compared with the main analysis. No significant differences in the number of adverse events were reported between the two groups, and none of the adverse events or deaths were related to the study treatments. The generalizability of this study was limited by its lack of use of stool tests after treatment, the possibility of bias from its open-label design, and a lack of comparison between FMT and fidaxomicin. Nevertheless, this study suggested that FMT was at least as effective as vancomycin in treating primary CDI.

Click to read this study in AIM

Relevant Reading: Fecal Microbiota Transplantation for Primary Clostridium difficile Infection

In-Depth [randomized controlled trial]: This phase III clinical trial aimed to compare the effectiveness of FMT versus vancomycin in treating primary CDI. Adult patients were enrolled from 20 hospitals in Norway and were eligible if they had primary CDI, defined as diarrhea, a positive stool result for toxin-producing C. difficile, and no diagnosis of CDI within 365 days prior to enrollment. Patients were excluded if they had other stool pathogens that could cause diarrhea, antibiotic treatments for other infections, inflammatory bowel disease, microscopic colitis, toxic megacolon, or ileus, among others. A total of 100 patients were randomly assigned in a 1:1 ratio to receive either a single FMT enema or oral vancomycin for 10 days. The primary end point was clinical cure 14 days after initiation of treatment – without need for additional treatments – and absence of recurrent CDI within 60 days after treatment. Clinical cure was defined as fewer than 3 stools a day or firm stools for at least 48 hours on day 14. At day 14, 36 (70.6%) FMT patients and 38 (77.6%) vancomycin patients showed clinical cure with the assigned treatment alone; however, 2 (5.6%) FMT patients and 8 (21.1%) vancomycin patients subsequently developed recurrence. As such, 34 (66.7% [95% CI, 52.1% to 79.2%]) FMT patients achieved clinical cure with the assigned treatment alone without recurrence versus 30 (61.2% [95% CI, 46.2% to 74.8%]) vancomycin patients, yielding a difference in treatment success of 5.4 percentage points (95.2% CI, -13.5 to 24.4). The total proportion of patients who achieved clinical cure without recurrence, with or without additional treatment, was 40 (78.4% [95% CI, 64.7% to 88.7%]) in the FMT group and 30 (61.2% [95% CI, 46.2% to 74.8%]) in the vancomycin group, yielding a difference in treatment success of 17.2 percentage points (95.2% CI, -0.7 to 35.1). The study reported 7 deaths (2 in the FMT group and 5 in the vancomycin group) within 60 days of follow-up, but none were related to the study treatments. Overall, FMT was shown to be at least noninferior to vancomycin in treating primary CDI.

Image: PD

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