A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial

Abstract

Faecal microbiota transplantation Neomycin a b s t r a c t Objectives: Intestinal carriage with extended spectrum b-lactamase Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) can persist for months. We aimed to evaluate whether oral antibiotics followed by faecal microbiota transplantation (FMT) can eradicate intestinal carriage with ESBL-E/CPE. Methods: Randomized, open-label, superiority trial in four tertiary-care centres (Geneva (G), Paris (P), Utrecht (U), Tel Aviv (T)). Non-immunocompromised adult patients were randomized 1: 1 to either no intervention (control) or a 5-day course of oral antibiotics (colistin sulphate 2 Â 10 6 IU 4Â/day; neomycin sulphate 500 mg 4Â/day) followed by frozen FMT obtained from unrelated healthy donors. The primary outcome was detectable intestinal carriage of ESBL-E/CPE by stool culture 35e48 days after randomization (V4). ClinicalTrials.gov NCT02472600. The trial was funded by the European Commission (FP7). Results: Thirty-nine patients (G ¼ 14; P ¼ 16; U ¼ 7; T ¼ 2) colonized by ESBL-E (n ¼ 36) and/or CPE (n ¼ 11) were enrolled between February 2016 and June 2017. In the intention-to-treat analysis 9/22 (41%) patients assigned to the intervention arm were negative for ESBL-E/CPE at V4 (1/22 not receiving the intervention imputed as positive) whereas in the control arm 5/17 (29%) patients were negative (one lost to follow up imputed as negative) resulting in an OR for decolonization success of 1.7 (95% CI 0.4 e6.4). Study drugs were well tolerated overall but three patients in the intervention group prematurely stopped the study antibiotics because of diarrhoea (all received FMT).

‘A five-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae’ – Author's reply

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We would like to thank Mullish et al for their letter regarding our study [1,2]. They rightly point out that the amount of faecal material (15e30 g of stool) used in patients treated with capsulized faecal microbiota transplant (FMT) was low and below the minimum of 30 g recommended in the 2017 European Consensus Conference on Faecal Microbiota Transplantation in Clinical Practicefor the treatment of recurrent Clostridium difficile infection (CDI) [3].

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Therapeutic Potential of the Gut Microbiota in the Management of Sepsis

“…Recently, a randomized controlled trial has been completed showing that patients given nonabsorbable oral antibiotics followed by FMT had a slight decrease in ESBL and CRE colonization compared with control patients, although without reaching statistical significance. The unfavorable results are potentially due to the study design (two different routes of FMT in the interventional group and contemporary antibiotic administration may have influenced carriage in the interventional group) and early trial termination [41]. However, it is important to note that so far none of the published studies has been conducted in ICU patients.…”

Transmission and clearance of potential procarcinogenic bacteria during fecal microbiota transplantation for recurrent Clostridioides difficile

“…Conversely, should future mechanistic studies confirm that these putative procarcinogenic bacteria are causally involved in human CRC or other disorders, our data suggest that FMT from donors who are negative for these organisms could be explored as a potential preventive/therapeutic approach. FMT has already shown some promise in non-rCDI patients as a tool to prevent or clear other individual pathogenic bacteria including antibiotic-resistant organisms, although with variable success (49)(50)(51). However, given that FMT itself is not risk free (e.g., there are risks associated with anesthesia for colonoscopy-delivered FMT), any such investigational studies should not be explored lightly, as the risks involved could very likely exceed any benefit.…”