During my long career as an orthopedic trauma surgeon for civilian and military patients, I've seen the significant negative impact of surgical site infections (SSIs) on patient outcomes and healthcare costs. For civilian patients, SSI rates can be up to 2 percent for Type 1 open fractures and up to 50 percent for Type 3. For military patients with trauma wounds, infection rates can be as high as 77 percent. These infections pose a substantial burden in terms of increased morbidity and mortality, as well as resource demand on the healthcare system.
U.S. data from the Centers for Disease Control and Prevention (CDC) indicate an average of 1.5 million SSIs per year, with a mean direct cost per case of $20,785 and a total burden of some $3.3 billion annually. In the case of periprosthetic joint infection, per-case costs can rise in excess of $100,000. This SSI burden includes an additional 11.2 days of ICU care per case.
Moreover, insurers have increasingly labelled SSIs as "never events," meaning that the facility will receive reduced or no compensation for resolving these cases. The cost of treating the SSI comes directly out of a facility's bottom line. Johns Hopkins conducted an analysis on 2007-10 data and found that preventing a single SSI could yield a net saving of over $34,000.
Those analyses all occurred well before the COVID-19 pandemic began to overload and overwhelm healthcare systems worldwide. Clearly, this extra burden poses a substantial risk to patients, caregivers and healthcare systems already under strain. It is critical to identify novel techniques and technologies to help alleviate the problem.
Treatment options for SSIs are generally either pharmacologic (antibiotics) or invasive (surgical debridement, irrigation and stabilization), yet have widely varying degrees of success. Both risk factors and predictors of success are multivariate and include pathogen(s) present, patient comorbidities, patient socioeconomic status and timing to detection and intervention. No single factor can predict whether a patient will develop or recover from an SSI. Therefore, a multi-pronged approach is warranted.
When pharmacotherapy alone is deemed insufficient, a common approach is open irrigation of the wound. The choice of irrigant has been hotly debated in scientific and clinical circles, and most traditional approaches include antibiotics (which biologically disrupt microflora) or antiseptics/detergents (which chemically or mechanically disrupt microflora). Each offers advantages and disadvantages; for example, antibiotics generally have lower host toxicity but offer differential impact on various microbiological species and risk formation of biological resistance. In 2020, the FDA requested voluntary market withdrawal of bacitracin for injection into irrigation solutions because of safety concerns and extremely limited use in pediatric pneumonia, its only approved indication. Antiseptics and detergents can offer broad spectrum coverage with low risk of resistance but potentially damage host tissues. A more nuanced approach may be useful in both balancing microbial susceptibility and secondary tissue injury.
One important factor in removing microbial contamination -- and hence resolving infections -- is whether the population has been able to form a biofilm in the site. Known since the 1970s, biofilms are now widely understood to form a protective niche for microbes in a wide variety of environments. In brief, microbes can accrete on a surface (ranging from a speck of dust to a biological surface to a petroleum pipeline) and synthesize extracellular polymeric substance (EPS) -- a complex milieu of polysaccharides, proteins, lipids and nucleic acids, cross-linked by metal ions. This protective EPS layer defends the colony from immune, antibiotic and antiseptic attack.
The challenges posed by biofilm-based SSIs, and the limitations of other treatment options, are why I'm excited to lead a U.S. clinical trial to test the efficacy of XPERIENCE™, a new no rinse antimicrobial solution that received FDA clearance in April. Developed by medical technology company Next Science, XPERIENCE is based upon Next Science's proprietary XBIO™ Technology, which takes an innovative approach to solving the problem of bacterial biofilms. The unique, non-toxic technology attacks and deconstructs the structure of the biofilm by removing the metal ions that hold the EPS together. This exposes the bacteria within the biofilm, making them more vulnerable to eradication. Bacteria that are enveloped within the XBIO Technology are then destroyed by the combination of a surfactant and high osmotic imbalance across the bacterial cell wall. XBIO Technology's broad-spectrum efficacy helps defend from biofilm reformation, reducing the rate of reoccurrence by over 100X. Due to this unique mechanism of action, there is no known resistance to XBIO Technology.
The trial, the TIFRAX (Tibial Fracture) Study, is a randomized, controlled, double-blinded, prospective study to evaluate the efficacy of XPERIENCE in helping decrease wound bioburden and surgical site infections. It will also evaluate whether XPERIENCE can improve post-operative outcomes when used as adjunct treatment to standard of care in patients undergoing tibial fracture repair. Enrolment in the 30-patient, 90-day study is already underway.
Robert M. Harris, MD is a board-certified orthopedic surgeon based in Columbus, Ga., where he is program director for the Jack Hughston Memorial Hospital Orthopedic Residency Program and co-director of the Hughston Orthopedic Trauma Fellowship for the Hughston Clinic at Midtown Medical Center. Harris attended the COS annual meeting in Nashville from Nov. 3-6 as a guest of Next Science, for whose XPERIENCE product he is currently leading a U.S. clinical trial.