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

Infections are a major complication in orthopedic and trauma surgery, leading to longer hospitalizations, reoperations, amputations, and higher healthcare costs. Fracture-related infections (FRIs) range from about 1–5% overall to as high as 33% in long-bone open fractures. Implant-associated infections are challenging due to biofilm formation on implants, which impedes systemic antibiotic penetration and increases non-union and implant loosening risks. Gram-positive organisms predominate in FRIs, particularly Staphylococcus aureus and other staphylococci. To prevent infection and reduce bacterial adhesion and colonization, local antibiotic prophylaxis strategies have been developed. Two clinically available systems are highlighted: (1) a fast-resorbable hyaluronic acid–polylactic acid-based antibiotic-loaded hydrogel (ALH; DAC), which can be loaded intraoperatively with antibiotics of the surgeon’s choice and releases them locally for approximately 72 hours; and (2) a premanufactured polylactic acid (PDLLA) gentamicin-coated tibial intramedullary nail (CN; PROtect), which releases most antibiotic within 48 hours. Evidence suggests combinations such as gentamicin plus vancomycin provide broad coverage for common FRI pathogens. The study’s objective was to evaluate the prophylactic efficacy and safety of antibiotic coatings (ALH and/or CN) in high-infection-risk fracture patients undergoing internal fixation or prosthetic replacement, and to assess effects on healing and complications.

The paper contextualizes prior research showing that antibacterial coatings can reduce bacterial colonization and biofilm formation in vitro and in vivo, and may be cost-effective. A randomized controlled trial of ALH applied to osteosynthesis hardware reported reduced surgical site infections compared with controls (0% vs 4.7%). Studies on gentamicin-coated tibial nails (ETN PROtect) in high-risk open fractures and complex revisions suggest reduced infection rates and potential cost savings. Combinations of local antibiotics (gentamicin + vancomycin) may cover over 90% of FRI pathogens with low resistance rates, whereas gentamicin monotherapy is less comprehensive. Evidence in periprosthetic fracture surgery is sparse; however, revision arthroplasty carries higher infection risks, underscoring the potential role for local prophylaxis. Overall, the literature supports prophylactic use of coatings in high-risk scenarios, while caution is advised when using coated nails to treat established infections due to mixed outcomes and costs.

Design: Retrospective observational single-center study at the Orthopedic Department of Policlinico Umberto I University Hospital. Population: Patients with appendicular skeletal fractures at increased risk of infection, treated between December 2017 and December 2020, undergoing internal fixation or prosthetic replacement with local antibiotic prophylaxis using one of the following: (1) gentamicin-coated intramedullary tibial nail (CN; PROtect Expert Tibial Nail, Synthes); (2) fast-resorbable polylactic-acid-based hydrogel loaded with antibiotics of choice applied intraoperatively to the implant (ALH; Defensive Antibacterial Coating, Novagenit); or (3) both. Inclusion criteria: Tibia fractures treated with CN; fractures treated with coated implants using ALH; ≥12 months clinical-radiographic follow-up; presence of increased infection risk (e.g., open fractures per Gustilo-Anderson, polytrauma, comorbidities/ASA risk, prior implants), quantified using the Wise et al. preoperative infection risk score. Data collected: Preoperative demographics (age, sex, BMI), comorbidities and habits (CCI and components), allergies, ASA class, fracture details (anatomic site, open fracture grading), estimated infection risk (Wise score). Intraoperative data (duration, site, procedure and implant type, perioperative systemic prophylaxis, bone graft use, surgical approach, coating type, local antibiotic used). Postoperative outcomes (length of stay, transfusion needs, FRI incidence per Matsemakers criteria, periprosthetic infection per EBJIS when applicable, other complications, SF-12 scores, radiographic healing and implant loosening/failure). Perioperative systemic prophylaxis: Cefazolin 2 g 30–60 min pre-incision (with intraoperative redosing if >3 h) plus two postoperative doses 8 h apart; clindamycin used for cephalosporin allergy; for open fractures, amoxicillin–clavulanate 2.2 g every 8 h from admission. Transfusion thresholds: Hb <8 g/dL (or <10 g/dL in cardiovascular disease). Coating preparation and application: ALH applied immediately before implant placement; standard dosing: one vial 5 mL hydrogel + gentamicin 200 mg. If more volume needed, two vials mixed: 5 mL + gentamicin 200 mg and 5 mL + vancomycin 250 mg. Manufacturer-tested dosages and elution used. CN is factory-coated PDLLA with embedded gentamicin sulfate, homogeneous surface coverage, releasing ~80% gentamicin in 48 h. Some CN cases also received ALH (5 mL with 250 mg vancomycin) adjunctively. Postoperative care: Early mobilization; partial weight bearing progression (skimming up to 3 weeks; partial-to-full load by ~8 weeks) as tolerated. Statistical analysis: Continuous variables summarized with mean, SD, and ranges; categorical as counts (%). Analysis conducted with IBM SPSS Statistics 26.

- Sample: 37 patients (20 male, 17 female); mean age 63.14 ± 24.84 years; BMI 24.86 ± 3.91; CCI 3.20 ± 2.77. Seven smokers (18.92%), three drug addicts (8.11%). - Trauma: 14 polytrauma (37.84%); 13 open fractures (GA I: 4; GA II: 5; GA IIIa: 2; GA IIIb: 1; GA IIIc: 1). Intraarticular fractures 43.24% (16/37). Prior implants present in 17 patients (45.9%), most commonly hip prostheses (11/17, 64.7%). - Estimated preoperative infection risk: Wise score mean 5.04 ± 2.44; mean local surgical site infection risk 6.4%. - Surgery: Mean operative time 194.59 ± 76.21 min. Coatings used: ALH alone in 27/37 (72.97%); CN alone in 4/37 (10.81%); both in 6/37 (16.22%). Local antibiotics: gentamicin alone in 27/37 (72.97%); gentamicin + vancomycin in 10/37 (27.03%). Minimally invasive/percutaneous approach in 8 cases; bone grafting in 3 cases (2 autologous, 1 synthetic). Blood transfusions required in 27/37 (72.97%). Mean length of stay 20.24 ± 17.14 days. - Follow-up: Mean 34.41 ± 9.46 months (minimum 12 months). - Primary outcome: FRI occurred in 1/37 patients (2.70%), lower than the preoperative estimated risk (6.4%). The single infection case was an open femoral shaft fracture (GA IIIB) in a high-risk 20-year-old male; organism was methicillin-sensitive, gentamicin-resistant Staphylococcus haemolyticus; managed successfully with staged debridement, antibiotic-loaded cement (gentamicin + vancomycin), targeted antibiotics, and later autologous bone grafting with infection resolution at 18 months. - Other complications: delayed union in 1 case (treated with nail dynamization); aseptic prosthetic loosening in 1 case (hip revision performed; PJI excluded). - Healing and function: Mean time to union 7.11 ± 2.71 months. SF-12 scores: MCS-12 47.85 ± 11.71; PCS-12 43.85 ± 10.25. - Subgroups: No infections among tibia fractures (most common injury, 12 patients) and periprosthetic fracture cases (11 patients).

The study addressed whether local antibiotic-coated implants reduce FRIs in high-risk fracture patients. The observed FRI rate (2.70%) was less than half the mean estimated preoperative risk (6.4%) based on the Wise score, indicating potential prophylactic benefit of coatings. Both systems have distinct advantages: ALH offers flexibility in antibiotic choice and applicability across implant types (including plates and prostheses), which is valuable when tailoring to local microbiology or patient allergies; however, its manual application may be nonuniform depending on implant geometry. The gentamicin-coated tibial nail provides uniform factory-applied coverage and ease of use for tibial nailing but limits antibiotic choice to gentamicin and to tibial nails only. No infections were observed in tibial fractures and periprosthetic fracture cases in this series, despite their inherently high infection risk profiles (e.g., open tibia fractures, revision-like periprosthetic procedures). These findings align with prior literature demonstrating that local antibiotic coatings can reduce bacterial colonization and infection rates and may lower costs and reoperations. Evidence suggests that combining gentamicin with vancomycin expands coverage to the majority of FRI pathogens with low resistance, supporting the authors’ use of combination therapy in some cases, particularly when larger implant surfaces required additional hydrogel volume. The low complication rate, absence of adverse effects attributable to coatings, acceptable union times, and favorable quality-of-life outcomes support the safety of these strategies. Nonetheless, the retrospective design, small heterogeneous cohort, and lack of a control group limit definitive causal inference, and longer follow-up would better exclude low-grade infections. Overall, the results support considering local antibiotic coatings as part of infection risk–reduction strategies in high-risk fracture surgery, with ALH offering broader applicability and coated nails providing practical, uniform coverage where available.

Antibiotic coatings used as local prophylaxis in high-risk fracture surgery were associated with a low FRI rate (2.70%), below the preoperative estimated risk, and showed no coating-related adverse effects. ALH is versatile and can be applied to diverse implants with antibiotics tailored to local epidemiology, while gentamicin-coated nails provide a practical, uniformly coated solution when applicable. Future randomized controlled trials with larger cohorts and longer follow-up are needed to confirm efficacy, optimize antibiotic selection (including combination regimens), and define indications across fracture types and implant constructs.

- Retrospective single-center design without a contemporaneous untreated control group limits causal inference. - Small and heterogeneous sample with varied fracture types, treatments, demographics, and comorbidities introduces confounding. - Follow-up minimum of 12 months may be insufficient to detect late or low-grade infections. - Manual application of hydrogel may result in nonuniform coating; the study did not quantify coating uniformity or elution in vivo. - Antibiotic choices predominantly included gentamicin (with or without vancomycin); results may not generalize to other antibiotic regimens or resistance patterns.