- no intervention [control]
- 5-day course of oral antibiotics (colistin sulphate 2 M IU 4x/day; neomycin sulphate 500mg 4x/day) followed by frozen FMT
Intestinal carriage with extended spectrum beta-lactamase (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.
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 M IU 4x/day; neomycin sulphate 500mg 4x/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).
39 patients [G=14; P=16; U=7; T=2] colonized by ESBL-E (n=36) and/or CPE (n=11) were enrolled between 02/2016 and 06/2017. 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) while in the control arm 5/17 (29%) patients were negative (1 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 overall well tolerated but 3 patients in the intervention group prematurely stopped the study antibiotics because of diarrhoea (all received FMT).
Non-absorbable antibiotics followed by FMT slightly decreased ESBL/CPE carriage compared to controls; this difference was not statistically significant, potentially due to early trial-termination. Further clinical investigations seem warranted.