Comparing the efficacy and safety of faecal microbiota transplantation with bezlotoxumab in reducing the risk of recurrentClostridium difficileinfections: a systematic review and Bayesian network meta-analysis of randomised controlled trials

Abstract

ObjectivesThe risk of recurrent Clostridium difficile infections (RCDIs) is high when treated with standard antibiotics therapy (SAT) alone. It is suggested that the addition of faecal microbiota transplantation (FMT) or bezlotoxumab after SAT reduces the risk of RCDI. In the absence of head-to-head randomised controlled trials (RCTs), this review attempts to compare the efficacy and safety of bezlotoxumab with FMT in reducing the risk of RCDI in hospitalised patients.DesignA systematic review and Bayesian network meta-analysis.Data sourceA comprehensive search from inception to 30 February 2019 was conducted in four databases (Medline/PubMed, Embase, Scopus, ClinicalTrials.gov).Eligibility criteriaRCTs reporting the resolution of diarrhoea associated with RCDI without relapse for at least 60 days after the end of treatments as the primary outcome.Data extraction and synthesisWe extracted author, year of publication, study design and binomial data that represented the resolution of diarrhoea or adverse events of monoclonal antibodies and FMT infusion. Random-effects models were used for resolution rate of RCDI and adverse events. The Cochrane Risk of Bias tool was used to assess the quality of included RCTs.ResultsOut of 1003 articles identified, seven RCTs involving 3043 patients contributed to the review. No difference was reported between single or multiple infusions of FMT and bezlotoxumab in resolving RCDI, (OR 1.53, 95% credible interval (CrI) 0.39 to 5.16) and (OR 2.86, 95% CrI 1.29 to 6.57), respectively. Patients treated with SAT alone or bezlotoxumab with SAT showed significantly lower rates of diarrhoea than FMT (OR 0, 95% CrI 0 to 0.09) and (OR 0, 95% CrI 0 to 0.19), respectively. There was no difference in terms of other adverse events.ConclusionsThis is the first network meta-analysis that has compared the recently Food and Drug Administration-approved monoclonal antibody bezlotoxumab with FMT for resolving RCDI. The quality of the included RCTs was variable. The findings of this study suggested no difference between single or multiple infusions of FMT and bezlotoxumab. However, FMT was associated with a higher rate of non-serious diarrhoea as opposed to SAT used alone or in combination with bezlotoxumab.

Fecal Microbiota Transplantation May Be the Best Option in Treating Multiple Clostridioides difficile Infection: A Network Meta-Analysis

“…FMT was not included to this analysis, since it is not recommended for primary infection. Other NMAs only investigated the efficacy of determined interventions (FMT, bezlotoxumab, only probiotics, only antibiotics or other antimicrobial agents [23,[25][26][27]), so our NMA can provide a more comprehensive result.…”

“…To rank and compare multiple treatments, a network meta-analysis may be the ideal choice. Although there have been network analyses (NMA) conducted on the efficacy of treatments in CDI [22][23][24][25][26][27], only one investigated a study population with mrCDI, which was restricted to the efficacy of different FMT methods [22]. Since there are many other therapeutic options available for treating rCDI, expansion of the network to pharmacological therapeutic modalities may provide further evidence when ranking treatments by efficacy.…”

Bezlotoxumab for Preventing Recurrent Clostridioides difficile Infection: A Narrative Review from Pathophysiology to Clinical Studies

“…They observed a greater risk reduction with FMT or monoclonal antibodies therapy, although any extrapolation about the relative efficacy of the different interventions should be made with caution because of the very different comparators employed in the included studies. In a Bayesian network meta-analyses of RCTs, a similar protective effect of bezlotoxumab versus (indirect comparison) single or multiple FMT was suggested, although FMT was possibly associated with a higher rate of non-serious diarrhoea as an adverse event (no differences were noticed for other adverse events) [67].…”

Clostridioides difficile infections in Saudi Arabia: Where are we standing?

“…The most hypervirulent strain detected during last decade was the North American pulsed-field gel electrophoresis type 1, restriction endonuclease analysis type B1, polymerase chain reaction ribotype 027, (NAP1/B1/027) and also referred to as ribotype 027 (RT027) which is also highly resistant to fluoroquinolones and metronidazole ( Fatima and Aziz, 2019 , Freeman et al, 2018 ). This strain has caused outbreaks in Europe and USA which brought the attention to CDI testing practice in hospitals, in terms of accuracy, specificity, and comprehensiveness as well as testing novel treatment options ( Alhifany et al, 2019 , Guh et al, 2020 ).…”

“…Hence, contact precautions with CDIs-infected patients is a must. Antibiotic treatment with intravenous or oral metronidazole (which is known for treating anaerobic bacterial infections) vancomycin (a glycopeptide antibiotic effective in CDIs when given orally only) or oral fidoxamycin remain the standard of care for initial episodes and subsequent recurrences, however, innovative adjunctive therapies such as fecal microbiota transplantation and bezlotoxumab have been proven effective in treating recurrent CDIs ( Alhifany et al, 2019 , McDonald et al, 2018 ).…”