Efficacy and Safety of Fecal Microbiota Transplantation in Treatment of Clostridioides difficile Infection among Pediatric Patients: A Systematic Review and Meta-Analysis

Abstract

Background and Aims: Cases of Clostridioides difficile infection have been rising among the pediatric and adolescent population. Fecal microbiota transplantation (FMT) has emerged as an alternative therapy for recurrent C. difficile infection. We aim to perform the first systematic review and meta-analysis investigating the safety and efficacy of fecal microbiota transplantation for C. difficile infection in children and adolescents. Methods: A literature search was performed using variations of the keywords “pediatrics”, “C. difficile infection”, and “fecal microbiota transplantation” in PubMed, EMBASE, CINAHL, Cochrane, and Google Scholar from inception to 30 June 2022. The resulting 575 articles were independently screened by three authors. Fourteen studies that satisfied the eligibility criteria were included in the meta-analysis. Results: The pooled success rate of FMT in the overall cohort was 86% (95% confidence interval: 77–95%; p < 0.001; I2 = 70%). There were 38 serious adverse events in 36 patients with a pooled rate of 2.0% (95% confidence interval: 0.0–3.0%; p = 0.1; I2 = 0.0%) and 47 adverse events in 45 patients with a pooled rate of 15% (95% confidence interval: 5.0–25.0%; p = 0.02; I2 = 54.0%). There was no death associated with FMT. Conclusions: FMT was concluded to be an effective and safe therapy in pediatric and adolescent patients with C. difficile infection. Underlying comorbidities may impede the efficacy. A rigorous screening process of the donors is recommended prior to embarking on FMT. There is no universal and cost-effective way to monitor the long-term outcomes of FMT. While promising, metagenomic sequencing may not be available in settings with limited resources. Robust data from randomized clinical trials is warranted.

Microbiome-Related and Infection Control Approaches to Primary and Secondary Prevention of Clostridioides difficile Infections

“…Even though the composition of the microbial species varies from donor to donor, successful prevention of CDI recurrences has been reported from 78 to 100% in one meta-analysis of 15 trials [ 91 ]. A meta-analysis of 14 studies (including RCTs, uncontrolled case reports, and case series) documented a pooled 86% cure (no CDI recurrences) with low adverse reactions (15%) and only 2% with serious adverse events [ 92 ]. Meta-analyses of FMT often pool results from phase 2 safety/formulation studies and phase 3 controlled trials, and CDI cure rates differ depending upon the study design (blinded controlled trials average 67.7% cure vs. 82.7% cure for open uncontrolled studies) [ 93 ].…”

“…Although early trials showed significant efficacy of FMT (averaging an 86% cure rate with 15% adverse events) for the recurrence of CDI, the procedure was unappealing to many patients and the risk of unidentified pathogens from the donor stool raised concerns with this procedure [ 92 ]. Another limitation is the heterogeneity of the microbial composition when different donors are used.…”

Unveiling the hidden world of gut health: Exploring cutting-edge research through visualizing randomized controlled trials on the gut microbiota

“…Among these, evaluating the safety and efficacy of fecal microbiota transplantation (FMT) was the main topic and received greater attention. FMT is a new therapy[ 46 , 94 ] being tested for autoimmune diseases[ 95 ], IBD[ 96 , 97 ], liver encephalopathy[ 98 ], and neurological disorders[ 99 ]. It has been extensively examined for recurrent Clostridium difficile infections[ 100 - 104 ].…”

Clostridioides difficile detection and infection in children: are they just small adults?

“…No deaths were attributed to FMT. The authors however discuss how little regulation and standardization exists regarding FMT, further highlighting the lack of randomized controlled clinical trials investigating its utility [59].…”