Fecal Microbiota Transplant Mitigates Adverse Outcomes Seen in Patients Colonized With Multidrug-Resistant Organisms Undergoing Allogeneic Hematopoietic Cell Transplantation.

Andrew J Innes,Dragana Milojkovic,Julie A K Mcdonald,Horace R T Williams,Eimear T Brannigan,Julian R Marchesi,Frances J Davies,Jiří Pavlů,Renuka Palanicawandar,Jane F Apperley,Richard M Szydlo,Rohma Ghani,Mark R Thursz,Edward J Kanfer,Eduardo Olavarria,Benjamin H Mullish

doi:10.3389/fcimb.2021.684659

Abstract

The gut microbiome can be adversely affected by chemotherapy and antibiotics prior to hematopoietic cell transplantation (HCT). This affects graft success and increases susceptibility to multidrug-resistant organism (MDRO) colonization and infection. We performed an initial retrospective analysis of our use of fecal microbiota transplantation (FMT) from healthy donors as therapy for MDRO-colonized patients with hematological malignancy. FMT was performed on eight MDRO-colonized patients pre-HCT (FMT-MDRO group), and outcomes compared with 11 MDRO colonized HCT patients from the same period. At 12 months, survival was significantly higher in the FMT-MDRO group (70% versus 36% p = 0.044). Post-HCT, fewer FMT-MDRO patients required intensive care (0% versus 46%, P = 0.045) or experienced fever (0.29 versus 0.11 days, P = 0.027). Intestinal MDRO decolonization occurred in 25% of FMT-MDRO patients versus 11% non-FMT MDRO patients. Despite the significant differences and statistically comparable patient/transplant characteristics, as the sample size was small, a matched-pair analysis between both groups to non-MDRO colonized control cohorts (2:1 matching) was performed. At 12 months, the MDRO group who did not have an FMT had significantly lower survival (36.4% versus 61.9% respectively, p=0.012), and higher non relapse mortality (NRM; 60.2% versus 16.7% respectively, p=0.009) than their paired non-MDRO-colonized cohort. Conversely, there was no difference in survival (70% versus 43.4%, p=0.14) or NRM (12.5% versus 31.2% respectively, p=0.24) between the FMT-MDRO group and their paired non-MDRO cohort. Collectively, these data suggest that negative clinical outcomes, including mortality associated with MDRO colonization, may be ameliorated by pre-HCT FMT, even in the absence of intestinal MDRO decolonization. Further work is needed to explore this observed benefit.

Highlights

There is mounting evidence that the gut microbiome directly impacts upon immune responses in patients with hematological malignancies (Schluter et al, 2020), and markedly influences clinical outcomes after hematopoietic cell transplantation (HCT) (Peled et al, 2020)
Nineteen patients were colonized with an multidrugresistant organisms (MDROs) prior to an allogeneic HCT
In our non-randomized retrospective analysis and subsequent matched-pair study, FMT mitigated the worse outcomes seen in MDRO-colonized post-HCT patients, including survival. Part of this appears likely attributable to FMT-related impact on infective complications after HCT

Summary

Introduction

There is mounting evidence that the gut microbiome directly impacts upon immune responses in patients with hematological malignancies (Schluter et al, 2020), and markedly influences clinical outcomes after hematopoietic cell transplantation (HCT) (Peled et al, 2020). The pretransplant gut microbiota is predictive of bloodstream infections during transplant; poorer outcomes are seen in patients who have intestinal colonization with multidrugresistant organisms (MDROs) (Samet et al, 2013), in terms of increased risk of multidrug-resistant bloodstream infection (BSI) (Cattaneo et al, 2018). Whilst pre-HCT screening for MDRO carriage may help empiric antimicrobial choice, the mortality of MDRO infection remains high (Cattaneo et al, 2018). Biological approaches that may restore the pre-HCT gut microbiota may be beneficial both from a hematological perspective, and for their potential in reducing MDRO titers

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