Beyond the Scalpel: Why Localized Drug Delivery Could Be the Key to Reducing Surgical Site Infections

A group of surgeons performing surgery in a hospital.

(Adobe Stock 187902458 by Jacob Lund)

As surgical site infections (SSIs) begin to rise again across health care systems, traditional prevention strategies are being tested and often found wanting. Dikla Czaczkes Akselbrad, the chief executive officer of PolyPid, believes it is time for a paradigm shift. In a candid interview with Infection Control Today^®(ICT^®), Akselbrad outlines the critical role localized drug delivery can play in closing the gap between perioperative protocols and real-world outcomes.

ICT: SSI rates are once again on the rise. What do you believe is the primary driver behind this troubling trend?
Dikla Czaczkes Akselbrad: The resurgence in SSI rates can largely be attributed to the growing challenge of antimicrobial resistance and the increasingly complex profiles of surgical patients. Hospitals are dealing with an aging population with multiple comorbidities, while bacteria are evolving faster than our ability to respond with effective antibiotics. The surgical environment has also become more demanding, with more high-risk procedures being performed on immunocompromised or chronically ill patients who are prime targets for SSI, which mainly occurs within the first 30 days following surgery.

ICT: In your view, why are existing SSI prevention strategies, such as systemic antibiotics and antiseptic protocols, falling short in today’s surgical environment?
DCA: Systemic antibiotics simply aren’t able to maintain effective concentrations at the surgical site for the duration required to prevent infection, especially in the most vulnerable postop window. Once an incision is made and the blood vessels are cut, the role of systemic antibiotics drops significantly. A local approach that is not reliant on systemic delivery can bypass this problem. Meanwhile, antiseptic protocols are only as effective as their consistent and proper application, which varies across surgical teams and institutions. Together, these approaches fall short because they lack durability, precision, and site-specific control.

ICT: What role do evolving patient factors (like comorbidities or antibiotic resistance) play in the growing incidence of SSIs?
DCA: They play a massive role. Patients with diabetes, obesity, or cancer already have compromised immune responses and impaired healing, which has been demonstrated time and time again in clinical trials. At the same time, we’re seeing more infections caused by multidrug-resistant organisms, which makes standard antibiotic regimens less effective. This convergence of host and microbial challenges makes SSI prevention increasingly complex.

ICT: How can hospitals better bridge the gap between perioperative protocols and actual patient outcomes to reduce infection rates?
DCA: Hospitals need to adopt more personalized and data-driven infection control strategies. That means integrating risk stratification tools, leveraging predictive analytics, and most importantly, utilizing technologies that deliver targeted and sustained antimicrobial action directly at the surgical site. Protocols are only as strong as their ability to adapt to the patient in front of you.

ICT: What does the latest research tell us about the limitations of systemic antibiotic delivery for SSI prevention?
DCA: The literature is clear: Systemic antibiotics often fail to reach and maintain sufficient concentrations at the wound site beyond the initial intraoperative window. Additionally, systemic exposure increases the risk of toxicity, damages the body’s microbiome, and contributes to the development of resistance. The most vulnerable time for infection, the first 30 days after the incision, is when systemic drugs are no longer present in effective levels. That’s why more must be done to enable antibiotics to consistently target the wound site over a longer period than is currently done.

ICT: Why is localized drug delivery emerging as a more promising strategy for SSI prevention, particularly in high-risk surgeries?
DCA: Localized delivery allows us to bypass systemic circulation and concentrate antimicrobial agents precisely where they’re needed at the surgical site. It offers prolonged protection, reduces systemic side effects, and limits resistance development. This approach is particularly impactful in high-risk procedures like colorectal, orthopedic, or oncological surgeries, where infection rates and consequences are highest.

ICT: What kinds of clinical outcomes are being seen with targeted, locally administered therapies in terms of infection reduction and healing time?
DCA: We’re seeing very encouraging data. In our Phase 2 trial, we’ve seen a 59% reduction (P = .0086) in SSI in colorectal surgery. In our first Phase 3 trial, we’ve seen a 55% reduction in infection in patients undergoing colorectal resection with a large incision. We are now in the last stages of a second Phase 3 pivotal trial with data expected at the end of June this year. These therapies not only prevent infections but also promote faster recovery, reduce reoperations, shorten hospital stays, and decrease overall health care costs.

ICT: How is PolyPid’s approach different from traditional antibiotic prophylaxis, and where are you seeing the most potential impact?
DCA: Our platform technology allows for controlled, localized release of antibiotics over an extended period for 30 days directly at the surgical site. Unlike systemic prophylaxis, which dissipates within hours, our approach maintains a therapeutic barrier precisely when and where it’s needed most. We're seeing the greatest potential in abdominal and oncological surgeries, where SSIs carry high morbidity and cost burdens.

ICT: What are the most significant barriers to widespread hospital adoption of localized biopharma solutions for SSIs?
DCA: Education and inertia. Many hospitals are still heavily reliant on traditional protocols and hesitant to adopt new technologies due to cost concerns or lack of familiarity. We also face regulatory and reimbursement challenges that can slow down integration, as it takes time to prove efficacy. However, once the clinical and economic benefits become clear, as they increasingly are, adoption accelerates.

ICT: Looking ahead to 2025 and beyond, what are the most urgent actions health systems should take to turn the tide on SSI rates?
DCA: Health systems must prioritize innovation in infection prevention, including the adoption of localized drug delivery technologies. This also means investing in better diagnostics, expanding stewardship programs, and ensuring perioperative teams are trained on advanced techniques. Ultimately, reducing SSI rates will require a proactive, multidisciplinary approach that integrates science, technology, and patient-centered care.