KPC-producing (KPCKP) is a threat for patients admitted to healthcare institutions. To assess the efficacy of several decolonization strategies for KPCKP rectal carriage. Observational study performed in a 750-bed university center from July to October 2018 on the efficacy of a 10-day non-absorbable oral antibiotic (NAA) regimen (colistin 10 mg/ml, amikacin 8 mg/ml, and nystatin 30 mg/ml, 10 ml/6 h) vs. the same regimen followed by a probiotic (Vivomixx®) for 20 days in adult patients with KPCKP rectal colonization acquired during an outbreak. Seventy-three patients colonized by KPCKP were included, of which 21 (29%) did not receive any treatment and 52 (71.2%) received NAA either alone ( = 26, 35.6%) or followed by a probiotic ( = 26, 35.6%). Eradication was observed in 56 (76.7%) patients and the only variable significantly associated with it was not receiving systemic antibiotics after diagnosis of rectal carriage 22/24 (91.6%) vs. 34/49 (69.3%), = 0.04. Eradication in patients receiving NAA plus probiotic was numerically but not significantly higher than that of controls 23/26 (88.4%) vs. 15/21 (71.4%), = 0.14 and of those receiving only NAA (OR = 3.4, 95% CI = 0.78-14.7, = 0.09). In an outbreak setting, rectal carriage of KPCKP persisted after a mean of 36 days in about one quarter of patients. The only factor associated with eradication was not receiving systemic antibiotic after diagnosis. A 10-day course of NAA had no impact on eradication. Probiotics after NAA may increase the decolonization rate, hence deserving further study.