A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial
B D Huttner, V de Lastours, M Wassenberg, N Maharshak, A Mauris, T Galperine, V Zanichelli, N Kapel, A Bellanger, F Olearo, X Duval, L Armand-Lefevre, Y Carmeli, M Bonten, B Fantin, S Harbarth, R-Gnosis WP3 study group, L Colle, F Kloosterman, W van Bentum-Puijk, J Vlooswijk, A Andremont, M Ben Hayoun, E Canoui, A Chabrol, N Gamany, M Lafaurie, A Lefort, R Lepeule, Z Louis, E Rondinaud, H Sadou Yayé, L Sarfati, V Zarrouk, C Brossier, L Carrez, V Lazarevic, G Renzi, E von Dach, S Cohen Percia, R Shvartz, J Lellouche, B D Huttner, V de Lastours, M Wassenberg, N Maharshak, A Mauris, T Galperine, V Zanichelli, N Kapel, A Bellanger, F Olearo, X Duval, L Armand-Lefevre, Y Carmeli, M Bonten, B Fantin, S Harbarth, R-Gnosis WP3 study group, L Colle, F Kloosterman, W van Bentum-Puijk, J Vlooswijk, A Andremont, M Ben Hayoun, E Canoui, A Chabrol, N Gamany, M Lafaurie, A Lefort, R Lepeule, Z Louis, E Rondinaud, H Sadou Yayé, L Sarfati, V Zarrouk, C Brossier, L Carrez, V Lazarevic, G Renzi, E von Dach, S Cohen Percia, R Shvartz, J Lellouche
Abstract
Objectives: Intestinal carriage with extended spectrum β-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 × 106 IU 4×/day; neomycin sulphate 500 mg 4×/day) followed by frozen FMT obtained from unrelated healthy donors. The primary outcome was detectable intestinal carriage of ESBL-E/CPE by stool culture 35-48 days after randomization (V4). ClinicalTrials.govNCT02472600. The trial was funded by the European Commission (FP7).
Results: Thirty-nine patients (G = 14; P = 16; U = 7; T = 2) colonized by ESBL-E (n = 36) and/or CPE (n = 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 0.4-6.4). Study drugs were well tolerated overall but three patients in the intervention group prematurely stopped the study antibiotics because of diarrhoea (all received FMT).
Conclusions: Non-absorbable antibiotics followed by FMT slightly decreased ESBL-E/CPE carriage compared with controls; this difference was not statistically significant, potentially due to early trial termination. Further clinical investigations seem warranted.
Keywords: Carbapenemase; Colistin; Extended-spectrum β-lactamase; Faecal microbiota transplantation; Neomycin.
Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
Source: PubMed