Probiotics for intestinal decolonization of ESBL-producing enterobacteriaceae; a randomized, placebo-controlled clinical trial

Abstract OBJECTIVES Infections with extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae (EPE) are a major healthcare concern. Our goal was to investigate whether a probiotic mixture could be used for eradication therapy in patients with prolonged intestinal EPE carriage. METHODS We performed a randomized, placebo-controlled single blinded clinical superiority trial in the south of Sweden between February 2017 and April 2019. Probiotic Vivomixx®, a mixture of 8 different living bacterial strains or placebo was given to adult outpatients intestinally colonized for at least three months with EPE. Patients with suspected active infections at the time of evaluation were excluded, immunosuppression, severe psychiatric disorder, drug abuse, or dementia. Each patient in the probiotic arm were administered 2 sachets (9.0 x 1011 live bacteria) twice daily for two months. The primary outcome was intestinal EPE eradication at the end of the one-year follow-up, as shown by three consecutive negative EPE rectal swabs during the follow-up year. The per protocol follow-up for all patients were 1, 3, 6 and 12 months after the initiation of the intervention. ClinicalTrials.gov Identifier: NCT03860415. RESULTS In total, the target size of 80 patients were included. The median age was 68 years in both groups. The number of females in the probiotics group were 23 (58 %) and in the placebo group 28 (70%). At the end of the trial, 12.5 % (5 out of 40) of the patients in the probiotic group had achieved successful eradication of EPE, as defined by the primary outcome, in the intention to treat analysis. In the placebo group, 5 % (2 out of 40) of the patients had achieved successful eradication of EPE (odds ratio 2,71; 95% confidence interval [CI], 0,49 to 14,9; p=0. 24). CONCLUSIONS Successful EPE eradication was observed in very few individualds. This trial did not support Vivomixx® as being superior to placebo for intestinal decolonization in adult patients with chronic colonization of EPE, but was limited in power.