Abstract Background The major reservoir of carbapenemase-producing Enterobacteriaceae (CPE) is the gastrointestinal tract of colonized patients. Colonization is silent and may last for months, but the risk of infection by CPE in colonized patients is significant. Methods Eight long-term intestinal carriers of OXA-48-producing Enterobacteriaceae (OXA-PE) were treated during 3 weeks with daily oral lactitol (Emportal^®), Bifidobacterium bifidum and Lactobacillus acidophilus (Infloran^®). Weekly stool samples were collected during the treatment period and 6 weeks later. The presence of OXA-PE was investigated by microbiological cultures and qPCR. Results At the end of treatment (EoT, secondary endpoint 1), four of the subjects had negative OXA-PE cultures. Three weeks later (secondary endpoint 2), six subjects were negative. Six weeks after the EoT (primary endpoint), three subjects had negative OXA-PE cultures. The relative intestinal load of OXA-PE decreased in all the patients during treatment. Conclusions The combination of prebiotics and probiotics was well tolerated. A rapid reduction on the OXA-PE intestinal loads was observed. At the EoT, decolonization was achieved in three patients. Clinical Trials Registration: NCT02307383. EudraCT Number: 2014-000449-65.