Clinical Outcomes of Metronidazole Monotherapy Versus Metronidazole Plus Clostridium butyricum MIYAIRI 588 Combination Therapy in Non-Severe Clostridioides difficile Infection: A Retrospective Cohort Study

Clostridioides difficile infection (CDI) remains a major healthcare-associated infection, and metronidazole (MNZ) is still used for selected patients with non-severe infection in Japan. Although Clostridium butyricum MIYAIRI 588 (CBM588) may be used as an adjunctive therapy, clinical evidence regarding its add-on value to MNZ in non-severe CDI remains limited. We conducted an exploratory single-center retrospective cohort study of adults with non-severe CDI treated with MNZ between April 2015 and March 2025. Of the 161 patients diagnosed with C. difficile infection, 53 patients met the eligibility criteria and were analyzed. Patients were categorized into MNZ monotherapy (n = 27) or MNZ plus CBM588 combination therapy groups (n = 26), and clinical outcomes were compared. Clinical cure was achieved in 51.9% of patients in the monotherapy group and 69.2% of patients in the combination therapy group; however, the difference was not statistically significant (p = 0.196). Recurrence was uncommon in both groups (3.7% vs. 0%), and exploratory multivariable analysis revealed that CBM588 use was not independently associated with clinical cure. These findings do not establish a definitive benefit of adjunctive CBM588 therapy and should be interpreted cautiously as hypothesis-generating given the limited sample size and non-significant result.