Surgical Antimicrobial Prophylaxis: Clinical and Economic Impacts on Surgical Site Infection Prevention and Healthcare System Sustainability

Background: Surgical antimicrobial prophylaxis (SAP) is a cornerstone of surgical site infection (SSI) prevention and represents one of the most cost-effective interventions in perioperative care. However, inappropriate antimicrobial selection, timing, dosing, and duration remain common, compromising clinical outcomes and increasing healthcare costs. This narrative review summarizes the clinical and economic impacts of SAP and its role in antimicrobial stewardship, value-based healthcare, and healthcare sustainability. Methods: A narrative review was conducted to synthesize current evidence on the clinical and economic impacts of SAP. The literature addressing the burden of SSIs, the clinical and economic impacts of prophylactic strategies, antimicrobial selection and duration, stewardship interventions, and future perspectives for optimizing perioperative infection prevention was reviewed. Results: Available evidence indicates that appropriate SAP reduces SSI-related morbidity and healthcare resource utilization, whereas inappropriate prophylaxis and prolonged antimicrobial exposure increase costs without improving outcomes. In a Brazilian microcosting study, deep sternal wound infection increased hospitalization costs by 152%, and mediastinitis by 188%, compared with uninfected patients. In orthopedic surgery, actual prophylaxis costs were approximately 11-fold higher than guideline-based regimens when inappropriate prescribing predominated. In neurosurgery, prolonged prophylaxis increased antimicrobial costs from US$3.35 to US$20.41 per patient, despite similar SSI rates (3.5% vs. 3.6%). Stewardship interventions have also demonstrated substantial economic benefits; one arthroplasty program improved optimal prophylactic antimicrobial selection from 64.9% to 95.4% and generated estimated savings of US$197,050 per 1000 procedures. Conclusions: Appropriate SAP is a high-value intervention that improves patient outcomes while reducing healthcare costs. Optimizing antimicrobial selection, timing, dosing, and duration through stewardship initiatives is essential to maximize clinical effectiveness, minimize unnecessary antimicrobial exposure, and promote sustainable healthcare systems. Future studies should incorporate standardized pharmacoeconomic methodologies to strengthen evidence-based decision-making and value-based surgical care.