Objective This study evaluated the clinical, epidemiological, and economic outcomes associated with the implementation of a multidisciplinary antimicrobial stewardship program (ASP) at the 24-bed Septic Surgery Unit of the Somogy County Kaposi Mór Teaching Hospital. The primary objective was to assess changes in direct antimicrobial procurement expenditures, consumption metrics, and healthcare-associated pathogen patterns, while monitoring 30-day all-cause mortality as a core safety endpoint. Methods In this quantitative retrospective before-after cohort study following the ORION and SQUIRE 2.0 guidelines, data from two one-year periods were evaluated: pre-intervention (1 October 2022 to 30 September 2023) and post-intervention (1 October 2023 to 30 September 2024). Evaluated metrics included Defined Daily Dose (DDD) per 1,000 patient-days, Days of Therapy (DOT) per 1,000 patient-days, mean overall duration of antibiotic (AB) therapy per treated patient, gross institutional procurement costs, length of stay (LOS), and 30-day all-cause mortality from admission. Group comparisons were analyzed using the Independent Samples t-test for continuous variables, and the Chi-square (χ²) test or Fisher’s exact test for categorical variables. Results Following ASP implementation, cumulative DDD increased by 23.00% (from 4,037.44 to 4,965.85 DDD, p = 0.003, 673.52 to 832.36 DDD/1,000 patient-days), while the total drug procurement cost decreased by 25.09% (from 6,451,451 HUF to 4,832,680 HUF, p = 0.006). Active AB exposure altered from 626.88 to 691.26 DOT per 1,000 patient-days. The mean duration of therapy per treated patient decreased from 5.68 (SD +/- 3.22) to 5.30 (SD +/- 3.23) days ( p = 0.028), and de-escalation practices improved, with reduced intravenous (IV) (80.00% to 71.15%) and increased oral treatment (PO) (20.00% to 28.85%, p < 0.001). The incidence density (ID) of glycopeptide-resistant Gram-positive cocci decreased by 87.07% ( p = 0.039), and methicillin-resistant staphylococci decreased by 74.13% ( p = 0.034), observed in conjunction with reinforced barrier infection control measures. All-cause 30-day mortality was 10.03% pre-intervention and 9.00% post-intervention ( p = 0.545), confirming non-inferior clinical safety. Conclusions Implementation of a multidisciplinary ASP in a septic surgery environment was associated with substantial direct cost savings, accelerated IV-to-PO conversion, and a reduced mean duration of patient therapy without compromising clinical safety, despite an administrative expansion in cumulative DDD metrics.
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