A network meta-analysis of randomized controlled trials exploring the role of fecal microbiota transplantation in recurrent Clostridium difficile infection

Theodore Rokkas, Javier P Gisbert, Antonio Gasbarrini, Georgina L Hold, Herbert Tilg, Peter Malfertheiner, Francis Megraud, Colm O'Morain, Theodore Rokkas, Javier P Gisbert, Antonio Gasbarrini, Georgina L Hold, Herbert Tilg, Peter Malfertheiner, Francis Megraud, Colm O'Morain

Abstract

Background: Recurrence remains a challenge in Clostridium difficile infection (CDI), and in this field fecal microbiota transplantation (FMT) has attracted significant interest. Network meta-analysis (NWM) has been established as an evidence-synthesis tool that incorporates direct and indirect evidence in a collection of randomized controlled trials. So far no NWM exists concerning therapeutic interventions for recurrent CDI (rCDI).

Objective: In this NWM we assessed the comparative effectiveness of various therapies for rCDI to examine the efficacy rank order and determine the optimum therapeutic approach.

Methods: A Bayesian network meta-analysis was performed to investigate the efficacy rank order of rCDI interventions.

Results: Six eligible RCTs were entered into an NWM. They included 348 rCDI patients, in whom seven therapeutic interventions were used, i.e. donor fecal microbiota transplantation (DFMT), vancomycin, fidaxomicin, vancomycin + DFMT, vancomycin + bowel lavage, autologous FMT and placebo. DFMT showed the highest efficacy in comparison with vancomycin [odds ratio (95% credible interval), 20.02 (7.05-70.03)] and fidaxomicin (22.01 (4.38-109.63)).

Conclusion: This NWM showed that DFMT is the optimum therapeutic approach for rCDI, as it was the most efficacious among various therapeutic interventions, particularly in comparison with commonly used antibiotics such as vancomycin or fidaxomicin.

Keywords: Fecal microbiota transplantation; network meta-analysis; recurrent Clostridium difficile infection; treatment.

© Author(s) 2019.

Figures

Figure 1.
Figure 1.
Flowchart of studies included in the network meta-analysis.
Figure 2.
Figure 2.
(a) Network map of recurrent Clostridium difficile infection interventions included in the randomized controlled trials. Node size reflects the number of patients randomly assigned to each treatment. Edge thickness is in proportion to the precision, i.e. the inverse of variance of each direct comparison. (b) Network forest plot. There was no significant inconsistency (p = 0.7). (c) Comparison-adjusted funnel plot. Treatment labels: A: DFMT (donor fecal microbiota transplantation); B: vancomycin; C: vancomycin + BL (bowel lavage); D: AFMT (autologous fecal microbiota transplantation); E: vancomycin + DFMT; F: placebo; G: fidaxomicin.
Figure 3.
Figure 3.
(a) Contribution plot for the comparisons network. The numbers represent the percentage contribution of the column showing direct comparisons to the row defining network meta-analysis estimates. (b) Bar graph depicting the risk of bias (RoB) for each network estimate. Light gray = low RoB, dark gray = unclear RoB, black = high RoB. (c) Quality matrix depicting the summary of RoB for each included study. Studies are identified by the number in the reference list. Treatment labels: A: DFMT (donor fecal microbiota transplantation); B: vancomycin; C: vancomycin + BL (bowel lavage); D: AFMT (autologous fecal microbiota transplantation); E: vancomycin + DFMT; F: placebo; G: fidaxomicin.
Figure 4.
Figure 4.
(a) Forest plot illustrating all possible pairwise comparisons of recurrent Clostridium difficile (rCDI) interventions according to their efficacies. The horizontal lines represent credible intervals (CrI). (b) League table showing the comparative efficacies of rCDI interventions. AFMT: autologous fecal microbiota transplantation; BL: bowel lavage; DFMT: donor fecal microbiota transplantation; OR: odds ratio.
Figure 5.
Figure 5.
(a) Rankograms for the recurrent Clostridium difficile intervention network showing the cumulative rank order for each intervention. (b) SUCRA: surface under cumulative ranking. Values for the six therapeutic interventions. AFMT: autologous fecal microbiota transplantation; BL: bowel lavage; DFMT: donor fecal microbiota transplantation.

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Source: PubMed

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