Fresh Versus Frozen Versus Lyophilized Fecal Microbiota Transplant for Recurrent Clostridium Difficile Infection A Systematic Review and Network Meta-analysis

Introduction:Clostridium difficile Infection is a significant source of morbidity and mortality, which is on the rise. Fecal Microbiota Transplantation (FMT) is an alternative therapy to antibiotics with a high success rate and low relapse rate. Current data regarding the efficacy of the types of FMT used, namely fresh, frozen, and lyophilized is conflicting. Our review attempts to consolidate this data and highlight the most efficacious treatment currently available. Methodology:MEDLINE, Embase, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, SciELO, the Korean Citation Index, and Global Index Medicus were systematically searched from inception through May 3, 2022. Studies in which patients are undergoing any form of FMT who had failed antibiotic treatment previously were included. Both pairwise (direct) and network (direct + indirect) meta-analysis were performed using a random effects model and DerSimonian-Laird approach. A frequentist approach was used for network meta-analysis. Risk differences with (RD) with 95% confidence interval (CI) were calculated. Results:A total of 8 studies, including 4 RCTs and 4 cohort studies, were included with a total of 616 patients. Fresh FMT was determined to be most successful with 93% efficacy 95% CI (0.913 to 0.999) followed by frozen with 88% efficacy 95% CI (0.857 to 0.947) and lyophilized with 83% efficacy 95% CI (0.745 to 0.910). The direct meta-analysis showed no statistically significant difference between fresh and frozen group. (RD -0.051 95% CI -0.116 to 0.014 P=0.178). No significant differences were noted in frozen versus lyophilized groups with an overall trend towards Fresh FM (RD -0.061 95% CI -0.038 to 0.160 P=0.617). On network meta-analysis, when compared with fresh group, a lower recovery rate was noted with both frozen group (RD -0.06 95% CI -0.11 to 0.00 P=0.05) and lyophilized group (RD -0.16 95% CI -0.27 to -0.05 P=0.01). Conclusion:We conclude the efficacy of Frozen and Lyophilized preparations is high with no difference in direct comparison, and the relative efficacy reduction based on network analysis is outweighed by the safety, accessibility, and practicality of Frozen or Lyophilized preparations.

Automated summary

Clostridium difficile Infection is a significant health problem with high morbidity and mortality. Fecal Microbiota Transplantation (FMT) is an alternative therapy with high success rate and low relapse rate. However, the efficacy of different types of FMT, such as fresh, frozen, and lyophilized, remains unclear. This review aims to consolidate the data and identify the most effective treatment.