Clostridioides difficile (C. difficile) is one of the bacteria listed as urgent threat by the US Centers for Disease Control and Prevention in 2019 [1]. C. difficile infection (CDI) mainly manifests as mild-to-moderate diarrhea, but sometimes as life-threatening diarrhea [2,3]. According to recent systematic reviews and meta-analyses, oral vancomycin administration exhibits high clinical cure rates against severe CDI [4,5]. Thus, oral vancomycin administration is globally recommended as the standard antibiotic therapy for patients with severe CDI [[6], [7], [8]]. However, the recurrence rate after vancomycin treatment is high [9,10], causing higher mortality rates, extended hospitalization, and higher medical costs [11,12]. Therefore, other therapeutic options that can lower the recurrence rates are required.

Teicoplanin has received considerable attention as a therapeutic alternative to vancomycin because clinical studies have reported that the effectiveness of oral teicoplanin administration is comparable to that of oral vancomycin administration in patients with CDI, and teicoplanin exhibits lower recurrence rates [[13], [14], [15]]. Thus, teicoplanin is a potential antibiotic candidate for CDI treatment, with better efficacy than vancomycin. However, the previous clinical studies included only a small number of patients with severe and life-threatening CDI; thus, the effect of teicoplanin treatment on lethal CDI is unclear. Although the incidence of severe and life-threatening CDI worldwide is increasing [3], teicoplanin cannot be used because of lack of scientific evidence. Teicoplanin is not globally approved for the treatment of CDI worldwide, except in some European countries [14,15]. Thus, the therapeutic efficacy of teicoplanin against severe CDI should be investigated for increased use of teicoplanin as a therapeutic agent for CDI; moreover, the number of studies on patients with severe and life-threatening CDI is small from an ethical point-of-view.

Therefore, the main objective of the present study was to investigate whether teicoplanin is a potent antibiotic against severe and life-threatening CDI in a mouse model. We assessed the physiological and biological responses of mice with lethal CDI to oral teicoplanin administration during the antibiotic treatment phase and the effect of teicoplanin on CDI recurrence. The antibiotic properties of teicoplanin against C. difficile were investigated in vitro to elucidate its antibiotic efficacy. All experimental data of teicoplanin obtained in this study were compared with those of vancomycin to determine whether the two antibiotics had different modes of action.