Pharmacoeconomics of Surgical Antimicrobial Prophylaxis: Impact on Surgical Site Infection Prevention and Healthcare System Sustainability

1. Introduction

Surgical site infections (SSIs) remain among the most common healthcare-associated infections worldwide and are associated with substantial clinical and economic consequences [1]. Despite advances in surgical techniques, perioperative care, and infection prevention measures, SSIs continue to contribute significantly to postoperative morbidity, prolonged hospitalization, readmissions, reoperations, and increased mortality [2]. Beyond their impact on patient outcomes, these infections impose a considerable financial burden on healthcare systems through increased resource utilization and higher treatment costs [3].

Surgical antimicrobial prophylaxis (SAP) is one of the most effective and widely adopted strategies for preventing SSIs [4]. When appropriately prescribed, including the correct antimicrobial agent, timing of administration, dosage, and duration, SAP has consistently demonstrated the ability to reduce the incidence of postoperative infections across a wide range of surgical procedures. Consequently, SAP has become a fundamental component of evidence-based perioperative care and an essential element of international guidelines for infection prevention.

The benefits of SAP extend beyond clinical effectiveness. The prevention of postoperative infections translates into reductions in hospital length of stay, antimicrobial consumption, diagnostic testing, intensive care utilization, and the need for additional surgical interventions. These outcomes have important economic implications, particularly in healthcare systems facing increasing financial constraints and growing demands for efficiency, quality, and sustainability [5].

In this context, pharmacoeconomics provides a valuable framework for evaluating the relationship between the costs and outcomes associated with healthcare interventions [6]. Through methodologies such as cost-effectiveness, cost-benefit, cost-minimization, and cost-utility analyses, pharmacoeconomic evaluations support decision-making processes by identifying interventions capable of generating the greatest health benefits while optimizing resource allocation [7]. The application of pharmacoeconomic principles to surgical antimicrobial prophylaxis is particularly relevant because relatively low-cost preventive interventions may avoid costly postoperative complications and improve overall healthcare value [8].

More recently, the growing adoption of value-based healthcare models has reinforced the importance of assessing both clinical outcomes and economic performance when implementing infection prevention strategies [9]. In this scenario, surgical antimicrobial prophylaxis represents a paradigmatic example of an intervention capable of simultaneously improving patient safety, reducing healthcare expenditures, and promoting sustainability within healthcare systems [10].

Therefore, this narrative review aims to discuss the current evidence regarding the pharmacoeconomic value of surgical antimicrobial prophylaxis, focusing on its impact on surgical site infection prevention, healthcare costs, antimicrobial stewardship initiatives, and the sustainability of healthcare systems.

2. Economic Burden of Surgical Site Infections

Surgical site infections represent one of the most frequent healthcare-associated infections and remain a major challenge for healthcare systems worldwide. For surgical patients, SSIs constitute most nosocomial infections and account for approximately 20% of all hospital-acquired infections [11]. Despite advances in perioperative care and infection prevention strategies, SSIs continue to be associated with significant morbidity, mortality, and healthcare expenditures. According to reports, SSIs account for almost one-third of postoperative fatalities globally, and it annually endangers the lives of millions of people and fuels the development of antibiotic resistance [12]. Their impact extends beyond clinical outcomes, generating substantial economic consequences for patients, healthcare institutions, and society.

The economic burden of SSIs can be categorized into direct, indirect, and intangible costs. Direct costs include expenditures related to additional antimicrobial therapy, diagnostic tests, surgical reinterventions, intensive care unit admissions, prolonged hospitalization, wound care management, and outpatient follow-up. Several studies have demonstrated that patients who develop SSIs require significantly greater healthcare resource utilization compared with non-infected surgical patients, resulting in considerable increases in treatment costs.

Among the most important contributors to the economic burden of SSIs is prolonged hospital length of stay. Badia et al. assessed the impact of SSI on health-cost of 26 publications from Europe, but the major issue was the homogeneity of data for cost-evaluation [13]. Studies have demonstrated that patients who develop SSIs may require an additional 7 to 10 days of hospital stay compared with uninfected surgical patients, largely due to the need for further diagnostic investigations, intravenous antimicrobial therapy, surgical reinterventions, and management of infection-related complications [14]. Moreover, the attributable cost of a single SSI has been estimated to range from approximately US$11,000 to over US$20,000 per case, depending on the type and severity of the infection [15]. These findings highlight the significant economic burden imposed by SSIs on healthcare systems and reinforce the importance of effective preventive strategies aimed at reducing postoperative infectious complications.

In addition to direct medical costs, SSIs generates important indirect costs associated with productivity losses, delayed return to work, long-term disability, and caregiver burden [16]. These consequences may persist long after hospital discharge and substantially increase the overall societal impact of postoperative infections. Furthermore, intangible costs, including pain, psychological distress, reduced quality of life, and decreased patient satisfaction, represent significant but often difficult-to-measure components of the total burden [1].

Several economic analyses have highlighted the financial consequences of SSIs across different surgical specialties. In orthopedic trauma, for example, infection following tibial fracture fixation has been shown to significantly increase resource utilization and overall treatment expenditures, resulting in treatment costs that can be up to 6.5 times higher than uninfected cases [17]. Similarly, cardiac surgeries usually require a hospital length of stay (LOS) of roughly 7 to 10 days. Developing SSI increases the total postoperative duration to an average of 37 to 59 days, often necessitating readmission to the intensive care unit [18].

Given the substantial clinical and economic consequences of SSIs, preventive interventions have become a priority for healthcare organizations worldwide. Effective prevention strategies not only improve patient outcomes but also contribute to more efficient resource utilization and greater sustainability of healthcare systems [19]. Within this context, surgical antimicrobial prophylaxis has emerged as one of the most cost-effective interventions for reducing the burden of postoperative infections and optimizing healthcare expenditures.

3. Cost-Effectiveness of Surgical Antimicrobial Prophylaxis

Surgical antimicrobial prophylaxis is widely recognized as one of the most cost-effective interventions for preventing SSIs [20]. By reducing the incidence of postoperative infections, SAP not only improves patient outcomes but also decreases healthcare costs estimated at $4.5–10 billion annually in the United States [21]. The relatively low acquisition cost of prophylactic antibiotics, when compared with the high costs associated with the diagnosis and treatment of SSIs, makes SAP an intervention with a highly favorable cost-effectiveness profile confirmed in several studies around the world [22,23]. Even modest reductions in SSI rates may result in significant cost savings [24]. Multiple studies, including a meta-analysis published in 2018 by Allen et al., have demonstrated that the financial costs associated with managing a single SSI often exceed the total costs of prophylactic antibiotic administration for hundreds of surgical procedures [25,26,27].

Evidence from systematic reviews and economic evaluations consistently supports the cost-effectiveness of preoperative antimicrobial prophylaxis across a variety of surgical specialties, with SSI rates ranging from 0 to 71.1% with costs amounting to US$480-22,130 [28]. These studies have shown that appropriate SAP reduces infection rates while simultaneously lowering overall healthcare expenditures. Importantly, the economic benefits are observed not only in high-risk procedures involving implants or prosthetic materials but also in many clean and clean-contaminated surgeries where infection prevention translates into meaningful reductions in postoperative complications.

The effectiveness of SAP depends on adherence to evidence-based principles, including appropriate antimicrobial selection, timing of administration, dosage, and duration. Failure to comply with established guidelines may compromise both clinical and economic outcomes. Inappropriate antibiotic choices, delayed administration, unnecessary redosing, and prolonged postoperative prophylaxis increase antimicrobial consumption and healthcare costs without providing additional protection against infection. Consequently, adherence to guideline-recommended practices is essential for maximizing the economic value of prophylactic interventions. A systematic review recovered 859 articles at the databases, with a total of 18 studies selected for synthesis, showing appropriate indication of antibiotic prophylaxis (ranging from 70.3% to 95%), administration of antibiotic at the correct time (ranging from 12.73% to 100%), correct antibiotic choice (ranging from 22% to 95%), adequate discontinuation of antibiotic (ranging from 5.8% to 91.4%), and adequate antibiotic prophylaxis (ranging from 0.3% to 84.5%) [29]. These data demonstrate that we are far from the ideal SAP considering a global panorama. How many SSIs could be avoided yearly, and the financial burden?

Several studies have demonstrated that shorter prophylactic regimens, including single-dose strategies, achieve comparable infection prevention outcomes to prolonged antibiotic courses in selected surgical procedures [30]. From a pharmacoeconomic perspective, reducing unnecessary antimicrobial exposure decreases medication expenditures, minimizes adverse drug events, lowers the risk of antimicrobial resistance, and reduces costs associated with monitoring and treatment-related complications [8]. These findings reinforce the principle that greater antibiotic use does not necessarily translate into greater clinical benefit (Table 1).

In addition to reducing direct healthcare costs, SAP contributes to broader economic benefits by improving surgical outcomes, reducing readmissions, accelerating patient recovery, and facilitating earlier return to normal activities [31]. Such benefits are particularly relevant in modern healthcare systems increasingly focused on value-based care, where interventions are evaluated according to their ability to improve outcomes while optimizing resource utilization [32].

4. Economic Impact of Appropriate Antimicrobial Selection and Duration

The selection of an appropriate antimicrobial agent should be guided by the most likely pathogens associated with the surgical procedure, local epidemiological patterns, patient-specific risk factors, and antimicrobial stewardship principles [33,34]. In most clean and clean-contaminated procedures, first-generation cephalosporins, particularly cefazolin, remain the preferred agents due to their efficacy against common skin flora, favorable safety profile, narrow antimicrobial spectrum, and low acquisition cost. The use of broader-spectrum antibiotics when not clinically indicated may increase drug expenditures, promote antimicrobial resistance, and expose patients to unnecessary adverse events.

Comparative studies have demonstrated that broader-spectrum agents do not necessarily provide superior protection against SSIs. In some surgical settings, first-generation cephalosporins have shown equivalent or even superior outcomes compared with third-generation cephalosporins while maintaining lower treatment costs (Figure 1). These findings reinforce the importance of evidence-based antimicrobial selection as a strategy to optimize both clinical outcomes and healthcare resource utilization [35].

The duration of prophylaxis represents another critical determinant of economic efficiency. International guidelines consistently recommend limiting prophylaxis to a single preoperative dose or discontinuing antibiotic administration within 24 hours after surgery for most procedures [36]. Despite these recommendations, prolonged postoperative prophylaxis remains common in many institutions, often driven by concerns regarding infection risk rather than scientific evidence [37].

Several studies have demonstrated that extending prophylaxis beyond the recommended duration does not significantly reduce SSI rates, even for implant-associated surgeries [38]. In contrast, a recent study from Saudi Arabia showed that prolonged antibiotic exposure increases medication costs, nursing workload, laboratory monitoring requirements, and the risk of antibiotic-related adverse events [39]. Additional consequences include Clostridioides difficile infection, drug toxicity, allergic reactions, and the emergence of antimicrobial resistance, all of which contribute to increased healthcare expenditures [40].

From a pharmacoeconomic perspective, unnecessary postoperative antibiotic administration represents a low-value practice because it generates additional costs without corresponding clinical benefits. Economic analyses have shown that adherence to guideline-recommended prophylaxis durations can significantly reduce antimicrobial consumption while maintaining equivalent infection prevention outcomes, even in developing countries [41].

The financial implications of inappropriate antimicrobial selection and prolonged prophylaxis extend beyond individual patients [42]. At the institutional level, excessive antimicrobial utilization contributes to higher pharmacy expenditures and increased costs associated with antimicrobial stewardship activities and infection control measures [43]. At the healthcare system level, inappropriate antimicrobial use accelerates the development of antimicrobial resistance, creating long-term economic burdens that affect future treatment options and healthcare sustainability [44,45,46,47,48,49].

5. Antimicrobial Stewardship and Value-Based Care

Antimicrobial stewardship programs (ASPs) have emerged as essential components of modern healthcare systems, aiming to optimize antimicrobial use while improving patient outcomes, minimizing adverse events, reducing antimicrobial resistance, and controlling healthcare expenditures [47,48]. Within the surgical setting, stewardship initiatives play a critical role in ensuring appropriate implementation of SAP, thereby enhancing both clinical effectiveness and economic efficiency. Considering the current AI-based models of applications, the surveillance can be more accurate [47,48,50].

Common issues include the use of unnecessarily broad-spectrum agents, incorrect timing of administration, inappropriate dosing, and prolonged postoperative prophylaxis. Giamarellou et al. published a recent narrative review of the ASP in hospital setting, including some aspects of the SSIs prophylaxis [51]. These practices increase antimicrobial consumption and healthcare costs without providing additional clinical benefit.

Numerous studies have demonstrated that stewardship interventions can significantly improve adherence to evidence-based guidelines for surgical prophylaxis [34,52,53,54,55,56,57,58]. Strategies such as prospective audit and feedback [59], clinical decision support systems [60], multidisciplinary protocol development [61], pharmacist-led interventions [62,63] , educational programs [64,65], and continuous performance monitoring have been associated with substantial improvements in prescribing practices. As a result, healthcare institutions frequently observe reductions in antimicrobial utilization, lower pharmacy expenditures, and improved compliance with recommended prophylaxis protocols.

The stewardship programs contribute to lower rates of surgical site infections, reduced hospital length of stay, fewer readmissions, and decreased utilization of diagnostic and therapeutic resources [65]. These improvements generate significant cost savings while simultaneously enhancing patient safety and quality of care, which can be crucial in developing countries, where sustainability of the healthcare system is essential [66].

The growing emphasis on Value-Based Healthcare (VBHC) further strengthens the importance of stewardship programs [67,68]. Value-based care focuses on maximizing patient outcomes relative to the costs incurred throughout the continuum of care [69,70]. In this framework, healthcare interventions are assessed not only by their clinical efficacy but also by their ability to generate meaningful health outcomes efficiently and sustainably. Surgical antimicrobial prophylaxis represents an excellent example of a high-value intervention, particularly when implemented within a structured stewardship framework [68].

From a value-based perspective, the success of SAP should not be measured solely by reductions in infection rates but also by its contribution to broader healthcare outcomes, including patient safety, quality of life, resource optimization, and long-term sustainability [71,72]. Stewardship programs facilitate this approach by promoting evidence-based decision-making and ensuring that antimicrobial use aligns with both clinical needs and economic considerations.

In addition, multidisciplinary collaboration is fundamental to the success of stewardship initiatives [73,74]. Surgeons, anesthesiologists, infectious disease specialists, pharmacists, microbiologists, infection prevention teams, and hospital administrators all contribute to the development and implementation of effective prophylaxis protocols. As healthcare systems worldwide face increasing financial pressures, aging populations, and rising antimicrobial resistance rates, the integration of antimicrobial stewardship principles into value-based care models becomes increasingly important. By simultaneously improving clinical outcomes and reducing unnecessary expenditures, stewardship programs support the sustainability of healthcare systems while reinforcing the principles of high-quality, patient-centered care.

Therefore, antimicrobial stewardship should be considered not only an infection prevention strategy but also a key component of value-based healthcare, capable of generating substantial clinical, economic, and societal benefits through the optimization of surgical antimicrobial prophylaxis practices.

6. Future Perspectives and Healthcare System Sustainability

The future of SAP extends beyond infection prevention and increasingly encompasses broader goals related to healthcare quality, economic efficiency, and system sustainability. As healthcare systems worldwide face rising costs, increasing surgical volumes, aging populations, and the growing threat of antimicrobial resistance, optimizing preventive strategies has become a strategic priority for policymakers, healthcare institutions, and clinical professionals [75,76].

One of the most promising developments in this field is the incorporation of precision medicine into perioperative infection prevention [77]. Traditional prophylactic protocols are generally based on procedure-specific recommendations and population-level risk estimates. However, advances in genomics, microbiome research, and predictive analytics may enable more individualized approaches to antimicrobial prophylaxis [78]. Future strategies may consider patient-specific characteristics, colonization status, microbiological risk profiles, and local epidemiological patterns to optimize prophylactic interventions while minimizing unnecessary antimicrobial exposure.

Artificial intelligence and machine learning technologies also have the potential to transform perioperative infection prevention [47,48]. Predictive models capable of identifying patients at increased risk for SSIs may support more targeted preventive measures, improve resource allocation, and enhance clinical decision-making [79]. Additionally, AI-driven clinical decision support systems may assist healthcare professionals in selecting the most appropriate antimicrobial agent, dose, timing, and duration based on real-time patient and institutional data [80]. However, the use of AI in SAP is still incipient, focused on infection control and prevention [81,82].

The increasing availability of electronic health records and healthcare analytics platforms provides new opportunities for monitoring compliance with prophylaxis guidelines and evaluating outcomes at both institutional and healthcare system levels [83]. Automated surveillance systems may facilitate the identification of prescribing patterns, benchmark performance indicators, and support continuous quality improvement initiatives [84]. Hartmann et al. showed the impact of inadequate surgical antibiotic prophylaxis on perioperative outcome and length of stay, with improvement using automated surveillance system [84]. These tools may contribute to more efficient antimicrobial stewardship programs and promote evidence-based practice across surgical specialties.

Another important area of future development involves the integration of pharmacoeconomic evaluations into routine healthcare decision-making. While the clinical benefits of SAP are well established, economic analyses remain heterogeneous and are often underrepresented in surgical research. Future studies should incorporate standardized pharmacoeconomic methodologies, including cost-effectiveness, cost-utility, and budget impact analyses, to better quantify the value generated by prophylactic interventions. Such evidence will be essential for informing policy decisions and resource allocation strategies in increasingly constrained healthcare environments.

7. Conclusion

Surgical antimicrobial prophylaxis represents one of the most effective and cost-effective strategies for preventing surgical site infections, reducing postoperative morbidity, mortality, healthcare resource utilization, and associated costs. The evidence reviewed demonstrates that appropriate antimicrobial selection, timing, dosage, and duration are critical for maximizing both clinical and economic outcomes. Furthermore, antimicrobial stewardship programs enhance the value of prophylactic interventions by promoting guideline adherence, reducing unnecessary antimicrobial use, mitigating antimicrobial resistance, and optimizing resource allocation. In the context of increasing healthcare expenditures and growing demands for quality and efficiency, surgical antimicrobial prophylaxis should be regarded not only as a cornerstone of infection prevention but also as a strategic component of value-based healthcare. Future advances in precision medicine, artificial intelligence, and healthcare analytics may further improve the effectiveness and sustainability of prophylactic strategies, reinforcing their role in supporting resilient and economically sustainable healthcare systems.