Antibiotic-Loaded Coatings to Reduce Fracture-Related Infections: Retrospective Case Series of Patients with Increased Infectious Risk

Fracture-related infections (FRIs) are a major complication in orthopedic surgery, increasing hospitalization, reoperations, amputations, and healthcare costs. The incidence of FRIs varies widely, ranging from 1.23–5% to 33% in long-bone open fractures. Implant-associated infections present a therapeutic challenge due to biofilm formation on implants, hindering antibiotic penetration and increasing the risk of non-union and implant loosening. Gram-positive bacteria, particularly Staphylococcus aureus, are frequently identified pathogens. To address this, local antibiotic delivery strategies, such as antibiotic-coated implants, are increasingly used. These include Defensive Antibacterial Coating (DAC®), a hyaluronic acid-polylactic acid gel with various antibiotics, and PROtect intramedullary tibial nailing, coated with gentamicin-loaded polylactic acid. Studies show that antibiotic coatings reduce bacterial colonization and biofilm formation in vitro and in vivo, and reduce infection rates in prophylaxis. However, ALH allows surgeon antibiotic choice but application might be less uniform than CN. This study aimed to evaluate the prophylactic efficacy of antibiotic coatings (ALH and CN) in reducing FRIs in high-risk trauma patients and assess their impact on fracture healing, prosthesis integration, and potential complications.

Existing literature demonstrates the effectiveness of antibiotic coatings in reducing bacterial colonization and biofilm formation, both in vitro and in vivo. Several studies have shown a reduction in the occurrence of infections when using these coatings as prophylaxis. There is also research on the cost-effectiveness of these coatings and their potential effects on fracture healing, prosthesis osteointegration, and limb function. However, the literature specifically focusing on the use of these coatings in trauma surgery, particularly in high-risk patients, remains limited. The existing studies often focus on specific implant types or use different methodologies, making direct comparisons challenging.

This retrospective, single-center observational study included 37 patients (20 males, 17 females) with appendicular skeletal fractures and increased infection risk treated between December 2017 and December 2020. Patients received osteosynthesis or prosthetic replacement with either gentamicin-coated tibial intramedullary nails (CN), antibiotic-loaded hydrogel (ALH) with gentamicin (alone or with vancomycin), or both. Inclusion criteria included tibia fractures treated with CN, fractures treated with ALH, at least 12 months of follow-up, and increased infection risk (defined by factors like diabetes, smoking, previous oncology history, etc.). Preoperative data collected included demographics, comorbidities (using Charlson Comorbidity Index), ASA risk score, and Wise et al. infection risk score. Intraoperative data included surgical duration, technique, implant type, and antibiotic used. Postoperative data included length of stay, transfusion needs, infection occurrence, complications (delayed consolidation, implant loosening), and SF-12 quality-of-life scores. Infection diagnosis followed Matsemakers et al. and EBJIS criteria. Statistical analysis used IBM SPSS Statistics 26 to analyze continuous and categorical variables.

The study included 37 patients with a mean age of 63.14 years and a mean preoperative infection risk score of 6.4%. ALH was used in 27 cases, CN in 4, and both in 6. Gentamicin was used in 72.97% of cases, and a combination of gentamicin and vancomycin in 27.03%. The mean follow-up was 34.41 months. Only one patient (2.70%) developed an FRI at 5 months post-surgery. This patient was a 20-year-old male smoker and drug abuser with a Gustilo-Anderson grade 3B open femur fracture, treated with ALH and gentamicin. The infection was caused by gentamicin-resistant Staphylococcus haemoliticus. The patient underwent a two-staged biological chamber technique with successful infection eradication. Two other patients experienced complications: one with delayed consolidation (treated with nail dynamization) and one with aseptic loosening of a hip prosthesis (requiring revision surgery). The mean time to fracture healing was 7.11 months, and the mean SF-12 scores were MCS-12 47.85 and PCS-12 43.85. The observed infection rate (2.70%) was significantly lower than the predicted rate (6.40%).

This study's results suggest that prophylactic use of antibiotic coatings significantly reduces FRI rates in high-risk fracture patients. The observed infection rate of 2.70% is considerably lower than the predicted rate of 6.40%, supporting the efficacy of this approach. While other studies have shown the benefit of antibiotic coatings, this study adds to the evidence base, especially in a high-risk trauma population. The use of ALH offers the advantage of antibiotic choice based on patient-specific risk factors. However, the less uniform application compared to CN should be considered. Although the observed infection rate was low, further larger and more robust studies are necessary to confirm these findings and definitively establish the optimal strategy for prophylaxis of FRIs.

This retrospective case series demonstrates the promising results of using antibiotic coatings (ALH and CN) as prophylaxis against FRIs in high-risk patients. The low infection rate observed (2.7%) compared to the predicted rate (6.4%) suggests a significant benefit. ALH's versatility is advantageous, but the more uniform application of CN offers a practical alternative where applicable. Future prospective, randomized controlled trials with larger sample sizes and longer follow-up periods are needed to validate these findings and explore optimal strategies.

The main limitations are the retrospective design, relatively small sample size, and heterogeneous patient population. The retrospective nature introduces potential biases. The limited sample size reduces statistical power, and the heterogeneity of fracture types and patient characteristics may confound the results. The relatively short follow-up period might not capture all late-onset infections. A prospective, randomized controlled trial with a larger, more homogeneous sample and extended follow-up would strengthen the conclusions.