Association of a Hospital-Wide Integrated Stewardship Intervention with Hospital-Acquired Multidrug-Resistant Organism Infection Incidence Density: A Large-Scale Interrupted Time-Series Study

Background: Hospital-acquired multidrug-resistant organism (HA-MDRO) infections remain a major patient-safety threat linked to antimicrobial exposure, but long-term hospital-level evidence on whether integrated stewardship can reduce HA-MDRO burden remains limited. Methods: We conducted a quasi-experimental interrupted time-series study at a large multi-campus tertiary teaching hospital in China. A hospital-wide integrated intervention combining diagnostic stewardship and antimicrobial prescribing stewardship was implemented on 1 November 2021. Monthly aggregated hospital data from July 2018 to December 2024, including 2,145,489 hospitalizations, were analyzed. The primary outcome was HA-MDRO infection incidence density per 1000 patient-days. Results: HA-MDRO incidence density decreased immediately at the start of the COVID period (IRR = 0.246; p < 0.001) and then increased over time (IRR per month = 1.074; p < 0.001). After intervention implementation, the post-intervention trend declined significantly relative to the COVID-period trajectory (IRR per month = 0.938; p < 0.001). Microbiological testing increased immediately and continued to rise (OR = 1.381 and 1.016 per month, respectively), whereas restricted antibiotic use declined after implementation (OR = 0.979 per month; all p < 0.05). The control outcome showed no consistent post-intervention change. Counterfactual analysis estimated that 15,274 HA-MDRO cases were averted over follow-up. Conclusions: A hospital-wide integrated stewardship intervention was associated with reversal of the increasing HA-MDRO trajectory observed during the COVID period, together with improved microbiological testing and reduced restricted antibiotic use. These findings support the value of integrating diagnostic and prescribing stewardship in high-volume tertiary hospital settings.