Data Sheet 1_Shengjiang Xiexin decoction combined with vancomycin for Clostridioides difficile infection: impact of vancomycin dose-reduction strategy on gut microbiota homeostasis and recurrence risk.docx

Even though relapse rates for Clostridioides difficile infection (CDI) are high, vancomycin—a medication that targets C. difficile and works well during acute episodes—has gut microbiota-disrupting effects. The Chinese herbal formula Shengjiang Xiexin decoction (SXD) is helpful for microbial reversion, justifying the use of combination therapy. One often invoked tactic in such bundles of care is to minimize patients’ antibiotic exposure. In this work, we challenged this paradigm in a murine CDI model. Divergently with regard to the dose deescalation (low-dose vs. short-course), we found that it significantly undermined the synergy between the drugs. Despite the resolution of acute symptoms by all combination regimens containing SXD, deescalation strategies (CDR2 and CDR3) resulted in significantly worse relapse, enhanced inflammation and sustained gut dysbiosis. Conversely, only the CDR1 regimen with SXD co-treatment resulted in a full recovery of gut microbiota alpha-diversity and long-term ecological stability, associated with a better shift of metabolic pathways. Accordingly, our key finding is that standard vancomycin dosing is necessary for this therapeutic synergy to be realized and that dose deescalation blunts it and raises the risk of relapse. Such evidence invites a more sophisticated antibiotic stewardship approach with concomitant treatments, favoring preservation of synergistic effect over simplistic dose reduction.