pathogens, modifying intestinal immune responses, and reducing the risk of infection [12][13][14][15]. Lactobacillus fermentum is one of the dominant Lactobacilli in a healthy woman's vaginal tract and intestine [16,17]. Previous studies have defined L. fermentum as a possible probiotic candidate for protecting the intestine against pathogens and regulating microfloral balance [18,19]. L. fermentum can inhibit intestinal pathogen growth by producing inhibitory compounds including H 2 O 2 , bacteriocin, and biosurfactants and improve intestinal bacteria flora by reducing Clostridium perfringens [20][21][22]. Moreover, other studies have reported that L. fermentum shows probiotic potential against gram-negative bacteria, including E. coli, Salmonella Typhimurium, and Klebsiella pneumoniae biofilm [23,24].CRE are gram-negative bacteria that seriously threaten public health, and infections due to these organisms are associated with significant morbidity and mortality [25]. Carbapenemase (including new Delhi metallo-β-Carbapenem-resistant Enterobacteriaceae (CRE) that produce Klebsiella pneumoniae carbapenemase are increasingly reported worldwide and have become more and more resistant to nearly all antibiotics during the past decade. The emergence of K. pneumoniae strains with decreased susceptibility to carbapenems, which are used as a last resort treatment option, is a significant threat to hospitalized patients worldwide as K. pneumoniae infection is responsible for a high mortality rate in the elderly and immunodeficient individuals. This study used Lactobacillus fermentum as a candidate probiotic for treating CRE-related infections and investigated its effectiveness. We treated mice with L. fermentum originating from the vaginal fluid of a healthy Korean woman and evaluated the Lactobacilli's efficacy in preventive, treatment, nonestablishment, and colonization mouse model experiments. Compared to the control, pre-treatment with L. fermentum significantly reduced body weight loss in the mouse models, and all mice survived until the end of the study. The oral administration of L. fermentum after carbapenemresistant Klebsiella (CRK) infection decreased mortality and illness severity during a 2-week observation period and showed that it affects other strains of CRK bacteria. Also, the number of Klebsiella bacteria was decreased to below 5.5 log 10 CFU/ml following oral administration of L. fermentum in the colonization model. These findings demonstrate L. fermentum's antibacterial activity and its potential to treat CRE infection in the future.