Local antimicrobial strategies in orthopaedic infection

Local antimicrobial strategies in orthopaedic infection address different operative problems, ranging from wound prophylaxis to implant-surface protection.

Local antimicrobial treatment in orthopaedic infection includes perioperative wound application, post-debridement carriers, bioactive glass in infected cavitary defects, implant-surface strategies, and bacteriophages in refractory infection. These approaches enter care in different operative settings and are best interpreted against the local problem they are intended to address.

Summary

  • Local antimicrobial treatment in orthopaedic infection is used in different operative and treatment settings, including perioperative wound prophylaxis, cavity management after debridement, implant-surface protection, and adjunctive treatment in refractory infection.

  • Antibiotic powders, carrier systems, bioactive glass, implant-surface technologies, and bacteriophages address different local problems, so efficacy data should be read within the operative setting in which each approach is used.

  • The most established orthopaedic evidence currently relates to local antibiotics used perioperatively, post-debridement carrier systems, and selected implant-surface or bioactive glass strategies. Published phage use in orthopaedic infection remains concentrated in small clinical series and case-based protocols.

  • The field is easiest to interpret by starting with the local problem: wound contamination at closure, a cavity after debridement, an implant surface at risk of colonisation, or refractory infection requiring organism-specific treatment.

Why local strategies are needed

In fracture-related and implant-associated infection, local biological and surgical conditions such as dead space, foreign material, and impaired local host factors can support bacterial persistence. Surgery therefore remains central, and local antimicrobial treatment is used as an adjunct to systemic therapy in both prophylactic and therapeutic settings (Metsemakers, 2020; Zimmerli, 2017).

Across these infections, three local problems recur during surgery and reconstruction.

  • After debridement, residual dead space can collect blood and fluid and leave a space in which bacteria persist.

  • Hardware is a foreign body that supports bacterial adhesion and biofilm formation.

  • In damaged or infected tissue, local antibiotic penetration may be reduced and the local host response may be impaired.

These operative problems are related, but they arise in different surgical settings. Local antimicrobial strategies therefore entered orthopaedic care as distinct approaches rather than as one uniform intervention.

Antibiotic powders and local antibiotic application

At wound closure in orthopaedic trauma, local antibiotic application is used to increase antimicrobial exposure directly within the surgical wound. In current practice, this usually means intrawound vancomycin powder applied at closure in fractures considered at increased risk of infection.

The most robust orthopaedic evidence relates to local antibiotic use for infection prophylaxis after open fractures. In pooled data from eight comparative studies including 2,738 patients with open limb fractures, infection occurred in 4.6% of patients treated with local antibiotics and in 16.5% of those without local antibiotics (Morgenstern, 2018). That finding needs careful interpretation, because six of the eight studies used antibiotic-loaded PMMA beads and only two evaluated local antibiotic application without a carrier. The pooled result therefore supports local antibiotic prophylaxis in open fractures more strongly than carrier-free powder alone (Morgenstern, 2018).

More specific evidence is available for intrawound vancomycin powder. In a randomised clinical trial of 980 patients with operatively treated high-risk tibial plateau or pilon fractures, 1000 mg of vancomycin powder reduced deep surgical site infection by 3.4% (O’Toole, 2021). The reduction was attributable to fewer gram-positive infections, while gram-negative-only infections were unchanged (O’Toole, 2021).

A retrospective study in high-risk tibial plateau fractures reported fracture-related infection in 3.8% with intrawound vancomycin compared with 10.9% without it, with no vancomycin-related complications reported during follow-up (Wang, 2023).

Published orthopaedic evidence for intrawound vancomycin powder is concentrated in perioperative trauma prophylaxis, particularly in high-risk tibial plateau and pilon fractures. The randomised tibial plateau and pilon fracture trial did not reduce gram-negative-only infections, so the available data do not support broad microbiological coverage from vancomycin powder alone (O’Toole, 2021). Generalisability is also restricted by the studied population, which was limited to high-risk tibial plateau and pilon fractures treated with plate-and-screw fixation (O’Toole, 2021). Use in practice varies substantially: in a multicentre observational analysis of 4,941 fractures across 28 trauma centres, vancomycin powder was used in 31% of cases overall, with higher use in open fractures and marked variation across centres and surgeons (Marchand, 2023).

Carrier systems after debridement

After debridement, the residual cavity becomes part of the treatment problem. Carrier systems are used in this setting to deliver local antimicrobial treatment into the debrided space while also contributing to dead-space management (McNally, 2022).

PMMA established the principle that a material placed into the post-debridement cavity can function as a local antibiotic depot. Its persistence, however, creates a different surgical pathway from a resorbable carrier because the material remains in situ unless it is removed. In a randomized trial comparing an antibiotic-impregnated bioabsorbable calcium sulphate substitute with antibiotic-loaded PMMA beads in chronic osteomyelitis and infected nonunion, infection eradication was 86% in both study arms, but subsequent procedures were more frequent with PMMA, 15 versus 7 (McKee, 2010).

Resorbable carriers are used in the same operative setting, but follow a different treatment logic. They are intended to provide local antimicrobial activity within the cavity and then resorb, avoiding the same planned removal problem. Comparative review data for calcium sulphate in chronic osteomyelitis suggest higher infection eradication and lower all-cause revision than comparator treatments, while wound leakage remains a recurring complication signal within this literature (Sheridan, 2022).

Prospective clinical data support the same post-debridement rationale for gentamicin-loaded ceramic carriers. In a series with mean follow-up of just over six years, 94% of patients were infection-free at final follow-up after single-stage surgery using a bioabsorbable gentamicin-loaded ceramic carrier, despite substantial host and infection complexity (McNally, 2022). Pharmacokinetic data support this treatment logic by showing high local gentamicin release with low systemic exposure, consistent with direct antimicrobial delivery into the debrided cavity (Stravinskas, 2016).

Carrier systems are therefore most appropriately interpreted as post-debridement tools for combined cavity management and local antimicrobial delivery. PMMA established that principle, while resorbable carriers changed its practical implications by reducing the need for planned removal and by supporting single-stage strategies in selected settings.

S53P4 bioactive glass

S53P4 bioactive glass is used after debridement in infected cavitary bone defects, where the residual void requires filling as part of infection surgery. In this setting, it functions as a bioactive bone void filler within the debrided defect. Its antimicrobial effect is attributed to local physicochemical changes generated by the glass rather than to elution of a loaded antibiotic (Claireaux, 2025; Nguyen, 2025).

The orthopaedic evidence base for S53P4 consists mainly of cohort studies, retrospective comparisons, and case series in chronic osteomyelitis, infected nonunion, and cavitary post-traumatic infection. A 2025 systematic review identified 24 observational studies with 957 patients treated for limb osteomyelitis or infected nonunion (Claireaux, 2025). A second 2025 systematic review and meta-analysis included 28 osteomyelitis studies with 1,122 patients and reported a pooled infection-eradication rate of 88.1% from 10 studies with at least 12 months of follow-up (Nguyen, 2025). The main limits of interpretation are the observational design of the included studies, heterogeneous surgical protocols, and variation in indication and defect type.

Reported outcomes in chronic cavitary osteomyelitis are consistent with the overall pattern in the literature. In a prospective multicentre cohort of 78 patients with chronic cavitary long-bone osteomyelitis, infection eradication was 85%, with 89% of patients infection-free at one year and 84% at two years; soft-tissue coverage was identified as a major risk factor for failure (Van Vugt, 2021). In a retrospective single-centre series of 24 chronic osteomyelitis cases and 14 septic nonunions, infection eradication was achieved in 22 of 24 osteomyelitis cases and both infection control and fracture healing were achieved in 11 of 14 septic nonunions, with prolonged serous drainage and wound dehiscence among the reported complications (Gatti, 2024). In a further retrospective comparison of chronic osteomyelitis and infected nonunion, reinfection occurred in 29% of the S53P4 group and 19% of the autologous bone graft group, while complete bone healing was observed in 77% and 78% respectively; multidrug-resistant pathogens were associated with more incomplete healing and a threefold higher risk of complications in both groups (Steinhausen, 2021).

Comparative studies provide a more useful basis for clinical interpretation. In chronic osteomyelitis with cavitary bone defects, recurrence and complication rates were similar between S53P4 and calcium sulphate antibiotic beads, with recurrence reported in 8.3% and 7.7% respectively after a mean follow-up of about 23 months (Ferrando, 2017). In a second retrospective comparison, infection control with S53P4 was similar to antibiotic-loaded calcium-based bone substitutes, while wound drainage and wound complications were less frequent in the S53P4 group (Romanò, 2014).

In orthopaedic infection surgery, S53P4 is most appropriately interpreted as a bioactive bone void filler used in infected cavitary defects after debridement. The review literature in that setting centres on infection control, defect filling, and bone healing, while interpretation remains dependent on observational evidence, variation in surgical context, and soft-tissue management (Claireaux, 2025; Nguyen, 2025).

Implant coatings

A. Fast-resorbable antibiotic-loaded hydrogel

A fast-resorbable antibiotic-loaded hydrogel can be applied to the implant surface at the time of surgery in order to provide short-term local antimicrobial protection during the early postoperative period. Within implant-surface strategies, this approach currently has the strongest clinical evidence. In a multicenter randomized trial in internal osteosynthesis for closed fractures, six surgical site infections occurred in the uncoated group and none in the hydrogel-treated group, without detectable interference with fracture healing or coating-related adverse events (Malizos et al., 2017). In a second multicenter randomized prospective study in primary and revision hip and knee arthroplasty, early surgical site infection occurred in 11 controls and one hydrogel-treated case, corresponding to 6.0% versus 0.6%, again without detectable interference with osteointegration (Romanò et al., 2017). The available evidence therefore supports this hydrogel-based approach primarily as a prophylactic implant-surface strategy rather than as a treatment modality for established long-bone infection (Malizos et al., 2017; Romanò et al., 2017).

B. Antibiotic-loaded PMMA-coated implants

Antibiotic-loaded PMMA-coated implants are used mainly when local antibiotic delivery and mechanical stabilization are required simultaneously after debridement, particularly in infected nonunion, fracture-related infection, and chronic osteomyelitis (Ismat, 2021; Walter, 2022). In a systematic review of antimicrobial-coated intramedullary nails for infected long-bone nonunions, overall infection eradication was 90.0% and bone consolidation 85.5% across 506 patients, most of whom were treated with PMMA-based coatings, but the literature consisted mainly of retrospective case series without control groups (Walter, 2022). A broader systematic review of implant cement coating techniques identified 607 reported cases and emphasized marked heterogeneity in implant cores, antibiotic combinations, coating methods, and outcome definitions, which limits cross-study comparison and generalisability (Ismat, 2021). Reported technical and implant-related complications include cement debonding, implant breakage, difficult extraction, and the broader limitations of PMMA as a non-resorbable carrier once antibiotic elution declines (Ismat, 2021; Metsemakers, 2020; van Vugt, 2019). The available evidence therefore supports these constructs primarily at the level of pragmatic reconstructive use rather than high-certainty comparative evidence (Ismat, 2021; Walter, 2022).

C. Gentamicin-coated tibial nails

Gentamicin-coated tibial nails are used mainly in open tibial fractures, nonunion revision, and selected fracture-related infection cases. In a systematic review, fracture fixation cases treated with a gentamicin-coated tibial nail showed four fracture-related infections among 114 patients, with bone healing in 94%, whereas revision cases showed four relapses and one new infection among 89 patients, with bone healing in 88%; no coating-related side effects were reported (De Meo et al., 2020). More recent cohort data suggest sustained infection reduction in open tibial fractures at two years, but the published literature remains focused largely on tibial indications (Zamorano et al., 2025). The available evidence therefore supports this technology most clearly as an intramedullary prophylactic or revision strategy in selected high-risk tibial cases, rather than as a broadly generalizable implant-surface solution (De Meo et al., 2020; Walter et al., 2021; Zamorano et al., 2025).

These implant-surface strategies should therefore be interpreted by indication and by evidence type. DAC is supported most strongly as a prophylactic implant-surface coating. Antibiotic-loaded PMMA-coated implants have broader treatment experience in established infection, but on substantially lower-quality evidence. Gentamicin-coated tibial nails represent an intermediate position, with more specific intramedullary indications and a more limited comparative literature, with more specific intramedullary indications and a more limited comparative literature (Malizos et al., 2017; Romanò et al., 2017; Ismat et al., 2021; De Meo et al., 2020).

Bacteriophages

Bacteriophages are bacteria-specific viruses that can be selected against an infecting pathogen and used as an adjunctive antimicrobial strategy. In orthopaedic infection care, they are an emerging adjunctive option rather than an established local strategy, and current clinical use has been reported mainly in difficult-to-treat musculoskeletal infections aafter failure or exhaustion of conventional surgical and antimicrobial treatment pathways (Metsemakers et al., 2023; Onsea et al., 2019).

The available human literature remains limited and heterogeneous. Most reports consist of case reports, small case series, or compassionate-use experiences, usually combining phage therapy with surgery and systemic antibiotics and using variable local, intra-articular, or intravenous administration routes (Metsemakers et al., 2023). In one early orthopaedic series using a standardized multidisciplinary pathway, four patients with severe musculoskeletal infection were treated with phage therapy and concomitant antibiotics, with no recurrence of the causative strains after a single treatment course at 8 to 16 months of follow-up (Onsea et al., 2019). A later referral-centre report from France described 23 patients with complex bone and joint infection treated under compassionate use, of whom 91% had relapsing infection and 87% had chronic prosthetic joint infection, indicating that current reported clinical use remains concentrated in salvage settings rather than routine practice (Ferry et al., 2021).

Interpretation nevertheless remains difficult. Outcomes cannot be separated easily from the accompanying surgical and antimicrobial treatment, standardized treatment protocols are still lacking, and phage selection is inherently pathogen-specific (Metsemakers et al., 2023; Onsea et al., 2019). 

A major translational issue is delivery. In orthopaedic infection, phages are often applied locally in an attempt to reach the implant surface or debrided wound more directly, but repeated administration through a drain or access system is operationally demanding and may itself create practical complications. In a preclinical fracture-related infection model, repeated local administration through a subcutaneous access tube was complicated by superinfection and by the development of neutralizing antibodies, whereas hydrogel-based delivery reduced immune exposure but did not yet establish a clearly superior therapeutic effect in established infection (Onsea et al., 2021). More recent reviews therefore focus not only on clinical case experience but also on delivery systems, formulation strategies, and pharmacokinetic uncertainty as central barriers to translation (Ortiz-Cartagena et al., 2025).

The current evidence therefore supports bacteriophages mainly as a highly individualized adjunctive option in selected refractory orthopaedic infections. (Metsemakers et al., 2023; Onsea et al., 2019; Ferry et al., 2021; Ortiz-Cartagena et al., 2025).

Practical implications for clinical decision-making

  • Interpret each approach against the operative problem it is intended to solve.

  • Antibiotic powders and direct wound application belong to a different part of the treatment pathway from post-debridement carrier systems.

  • Bioactive glass (S53P4) belongs in the same overall field as local antibiotic options, while following a different logic from antibiotic loading and elution.

  • Implant coatings are best understood through implant protection, bacterial adhesion, and early biofilm control at the device surface.

  • Bacteriophages extend the field beyond conventional antibiotic delivery and remain early in clinical development for orthopaedic infection care.

Common pitfalls

  • Treating local antimicrobial treatment as though it were a single intervention.

  • Comparing powders, post-debridement carriers, bioactive glass, implant-surface strategies, and phages without first defining the operative setting.

  • Interpreting carrier systems as intensified wound prophylaxis instead of post-debridement treatment linked to cavity management.

  • Interpreting S53P4 as an antibiotic carrier instead of a bioactive bone void filler used in infected cavitary defects.

  • Interpreting phage therapy as though it were supported by the same level of standardised orthopaedic evidence as established local antibiotic strategies.

Closing note

Local antimicrobial treatment in orthopaedic infection is not a single intervention, but consisting of several strategies that enter care in different operative settings. Powders, post-debridement carriers, bioactive glass, implant-surface technologies, and bacteriophages should therefore be interpreted against the local problem they are intended to address and the level of evidence supporting that use.

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