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Background: Whether antimicrobial stewardship programs (ASPs) modulate the association between antimicrobial use and resistance remains uncertain. Long-term evidence for precision stewardship models in Chinese tertiary hospitals is scarce. Methods: A 7.5-year interrupted time-series analysis (2018– 2025) was conducted at a 1900-bed Chinese tertiary hospital. A pharmacist-led, grid-based precision ASP—stratifying 29 departments via Boston Matrix and integrating four synergistic pillars—was implemented in July 2020. Segmented regression models, adjusted for seasonality and autocorrelation, evaluated changes in antimicrobial use density (AUD), clinical/economic outcomes, and the temporal association ( R 2 ) between AUD and multidrug-resistant organism (MDRO) detection rates. Results: The ASP was associated with an immediate AUD reduction (− 25.6%, β 2 = − 14.55 DDDs/100 patient-days, P < 0.001) and a sustained decline in antimicrobial use rate ( β 3 = − 0.003, P < 0.001). Key antimicrobial classes showed marked reductions (fluoroquinolones: − 40.2%; carbapenems: − 16.1%). The ASP was also associated with improved clinical outcomes, including shorter median length of stay (10.9 to 8.8 days), 52% lower all-cause mortality (0.79% to 0.38%, P < 0.001), and declining per capita antimicrobial costs ( β 3 = − 19.39 CNY/month, P < 0.001). Notably, the AUD-MDRO temporal association varied across pathogens: R 2 for MRSA, CREco, and CRAB decreased by 71.8% to 87.0%, moderately weakened for CRKP (49.8%), but paradoxically strengthened for CRPA (+78.3%). Conclusion: This grid-based precision ASP was associated with sustained reductions in antimicrobial use and costs, and improved clinical outcomes. It was also associated with changes in the temporal relationship between AUD and MDRO detection rates. These alterations suggest this approach may mitigate selective pressure driving resistance, although causality cannot be established in this observational study. This framework may serve as a policy-aligned reference for large tertiary hospitals and provide useful insights to inform local and national antimicrobial stewardship initiatives. Keywords: temporal association, antimicrobial stewardship, pharmacist-led intervention, grid-based precision management, interrupted time-series analysis, multidrug-resistant organism
Zhao et al. (Fri,) studied this question.