Abstract
BACKGROUND: Inappropriate antibiotic use drives antimicrobial resistance (AMR). Performing pathogen detection before initiating antimicrobial therapy is essential for antimicrobial stewardship (AMS), enabling targeted treatment. Robust evidence on multifaceted interventions' sustained impact on pre-therapy pathogen detection specimen submission rates, AMS metrics, and multidrug-resistant organisms (MDROs) is limited. METHODS: Interrupted time series analysis evaluated a comprehensive AMS intervention (April 2023) at a tertiary care hospital in China (April 2022-May 2025). Interventions included: team establishment, lab expansion, education, electronic restrictions for restricted/special use-levels antibiotics (mandating pre-therapy pathogen detection specimen submission rate), audit/feedback, and monitoring. Segmented regression assessed level (immediate) and slope (trend) changes in pre-therapy pathogen detection specimen submission rate, antimicrobial use, costs, and MDRO isolate rates. RESULTS: Post-intervention, overall pre-therapy pathogen detection specimen submission rate increased immediately (+9.82%, P=0.009) with sustained monthly growth (+1.21%, P<0.001); increases occurred across all antimicrobial classes (all P<0.05). Antimicrobial use intensity reversed significantly from a pre-intervention upward trend (β(1) = +1.22 DDDs/100PD, P=0.002) to a sustained downward trajectory (β(3) = -1.36, P=0.001), with non-restricted agents showing the steepest decline (net slope = -0.16). Concurrently, antimicrobial utilization rate, per capita costs, and cost proportion reversed to downward trends (all P<0.05), while testing costs remained stable Only carbapenem-resistant Klebsiella pneumoniae (CRKP) exhibited sustained reduction (-0.87%/month, P=0.013); other MDROs showed no significant changes. CONCLUSION: The intervention significantly improved pre-therapy pathogen detection specimen submission rate and optimized antimicrobial use (reduced intensity/costs), but demonstrated limited resistance impact beyond CRKP reduction. Sustainable AMR control requires integrating diagnostic stewardship with infection prevention programs.