Authors:
Benedikt Huttner (Geneve | CH)
Victoire De Lastours (Paris | FR)
Marjan Wassenberg (Utrecht | NL)
Nitsan Maharshak (Tel Aviv | IL)
Anne Mauris (Genève | CH)
Tatiana Galperine (Geneva | CH)
Veronica Zanichelli (Geneva | CH)
Nathalie Kapel (Paris | FR)
Agnes Bellanger (Paris | FR)
Flaminia Olearo (Geneva | CH)
Xavier Duval (Paris | FR)
Antoine Andremont (Paris | FR)
Yehuda Carmeli (Tel Aviv | IL)
Marc Bonten (Utrecht | NL)
Bruno Fantin (Paris | FR)
Stephan Harbarth (Geneva | CH)
Background: Fecal microbiota transplantation (FMT) has been suggested to eradicate intestinal carriage with Extended spectrum beta-lactamase (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE).
Materials/methods: This publically funded, multicenter (Geneva [G], Paris [P], Utrecht [U], Tel Aviv [T]) open-label, randomized trial examined whether a 5-day course of oral antibiotics followed by FMT is superior to no intervention for the eradication of intestinal carriage of ESBL-E and/or CPE. Adult, immunocompetent patients with ESBL-E or CPE carriage were eligible. Patients were randomized 1:1 to either 5 days of colistin sulphate 2 million IU per os 4x/day & Neomycin sulphate 500 mg (salt) per os 4x/day for 5 days followed by FMT (either by administration of 15 FMT capsules on two consecutive days [G, P] or by a single administration of 80ml of faecal material via nasogastric tube [U,T]). FMT was obtained from healthy, unrelated donors [G, P, U] or from a stool bank [T]. Stool cultures for ESBL-E/CPE carriage were obtained 8-15 days [V2], 16-28 days [V3], 35-48 days [V4, primary outcome] and 5-7 months [V5] after randomization. The targeted sample size was 16 patients per centre. The primary analysis was “intention-to-treat”. ClincalTrials.gov NCT02472600.
Results: Between 02/2016-06/2017 39 patients were randomized [G=14; P=16; U=7; T=2], 22 to the intervention (21/22 underwent the intervention) and 17 to the control. Recruitment stopped in 06/2017 due to lack of further funding. Median age was 65 years (range 22-89), 20 were female, 36 of 39 patients were colonized with ESBL-E and 11 with CPE (8 had both). Of the 22 patients in the intervention arm, 9 (41%) were negative for ESBL-E/CPE at V4. In the control arm, 4 patients were negative (24%), 12 positive and 1 was lost to follow-up (imputed as negative). The intervention had no significant effect (OR for decolonization; 2.0 [95%CI 0.5-7.6]). Study drugs were overall well tolerated.
Conclusions: While this clinical trial failed to achieve its targeted sample size, the results suggest only a small effect of oral non-absorbable antibiotics followed by FMT on the eradication of intestinal carriage of ESBL-E and/or CPE.