TY - JOUR
T1 - A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae
T2 - a randomized clinical trial
AU - Huttner, B. D.
AU - de Lastours, V.
AU - Wassenberg, M.
AU - Maharshak, N.
AU - Mauris, A.
AU - Galperine, T.
AU - Zanichelli, V.
AU - Kapel, N.
AU - Bellanger, A.
AU - Olearo, F.
AU - Duval, X.
AU - Armand-Lefevre, L.
AU - Carmeli, Y.
AU - Bonten, M.
AU - Fantin, B.
AU - Harbarth, S.
AU - Colle, L.
AU - Kloosterman, F.
AU - van Bentum-Puijk, W.
AU - Vlooswijk, J.
AU - Andremont, A.
AU - Ben Hayoun, M.
AU - Canoui, E.
AU - Chabrol, A.
AU - Gamany, N.
AU - Lafaurie, M.
AU - Lefort, A.
AU - Lepeule, R.
AU - Louis, Z.
AU - Rondinaud, E.
AU - Sadou-Yaye, H.
AU - Sarfati, L.
AU - Zarrouk, V.
AU - Brossier, C.
AU - Carrez, L.
AU - Lazarevic, V.
AU - Renzi, G.
AU - von Dach, E.
AU - Cohen Percia, S.
AU - Shvartz, R.
AU - Lellouche, J.
N1 - Funding Information:
This study was part of the European R-GNOSIS ?Resistance in Gram-Negative Organisms: Studying Intervention Strategies? collaborative research project funded by the European Commission under the Seventh Framework Programme (FP7/2007) for Research and technology (Grant Agreement no. 282512). We would like to thank all the patients, donors and medical personnel involved in the study. Furthermore, we would like to thank the following colleagues and institutions without whose support this trial would not have been possible: Annecy: Jean-Pierre Bru; Boston: Elizabeth Hohmann, Hannah Systrom; Dijon: Centre National de R?f?rences des virus ent?riques; Geneva: Fabricio Jantarada, Dani?le Schaerrer, Ilker U?kay; Lausanne: Beno?t Guery, Thierry Calandra; Paris: Khadidja Berrouane, Estelle Marcault, Isabelle Vivaldo, Loubna Alavoine, Mich?le Benhayoun, Institut Pasteur and Institut de veille sanitaire fran?ais (Alexandre Leclercq, Marie Laure Quilici); Tel Aviv: Meital Kazma, Shimrit Cohen Percia, Gal Schtrechman Levi; Swissmedic: Julia Djonova, Constanze Fritzsche; and Eurofins: Elodie Lanois. This study has also received contributions from the Clinical Research Centre, Geneva University Hospitals and Faculty of Medicine, Geneva (special thanks to Serenella Ferro Rojas and Khaled Mostaguir).
Funding Information:
This study was part of the European R-GNOSIS ‘Resistance in Gram-Negative Organisms: Studying Intervention Strategies’ collaborative research project funded by the European Commission under the Seventh Framework Programme (FP7/2007) for Research and technology (Grant Agreement no. 282512 ).
Publisher Copyright:
© 2019 The Authors
PY - 2019/7
Y1 - 2019/7
N2 -
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 × 10
6
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.gov NCT02472600. 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.
AB -
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 × 10
6
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.gov NCT02472600. 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.
KW - Carbapenemase
KW - Colistin
KW - Extended-spectrum β-lactamase
KW - Faecal microbiota transplantation
KW - Neomycin
KW - Extended-spectrum beta-lactamase
UR - https://www.scopus.com/pages/publications/85061796742
U2 - 10.1016/j.cmi.2018.12.009
DO - 10.1016/j.cmi.2018.12.009
M3 - Article
AN - SCOPUS:85061796742
SN - 1198-743X
VL - 25
SP - 830
EP - 838
JO - Clinical Microbiology and Infection
JF - Clinical Microbiology and Infection
IS - 7
ER -