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, L. Colle, F. Kloosterman, W. van Bentum-Puijk, J. VlooswijkA. Andremont, M. Ben Hayoun, E. Canoui, A. Chabrol, N. Gamany, M. Lafaurie, A. Lefort, R. Lepeule, Z. Louis, E. Rondinaud, H. Sadou-Yaye, L. Sarfati, V. Zarrouk, C. Brossier, L. Carrez, V. Lazarevic, G. Renzi, E. von Dach, S. Cohen Percia, R. Shvartz, J. Lellouche

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.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.

Original languageEnglish
Pages (from-to)830-838
Number of pages9
JournalClinical Microbiology and Infection
Volume25
Issue number7
DOIs
StatePublished - Jul 2019

Funding

FundersFunder number
FP7/2007
Faculty of Medicine, Geneva
Gal Schtrechman Levi
Shimrit Cohen Percia
Seventh Framework Programme282512
European Commission
Institut Pasteur
Seventh Framework Programme
Hôpitaux Universitaires de Genève
Institut de Veille Sanitaire

    Keywords

    • Carbapenemase
    • Colistin
    • Extended-spectrum β-lactamase
    • Faecal microbiota transplantation
    • Neomycin

    Fingerprint

    Dive into the research topics of 'A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial'. Together they form a unique fingerprint.

    Cite this