Introduction: The Challenge of PJI

Total joint arthroplasty (TJA) is the gold standard for end-stage osteoarthritis of the hip and knee, but periprosthetic joint infection (PJI) remains one of its most challenging complications, affecting 2-3% of primary procedures (Baums et al. 2023; Giai Via et al. 2024). PJI is diagnostically difficult because of heterogeneous clinical presentations, variable organism virulence, host-specific factors, and an evolving, still incomplete understanding of biomarkers; the 2018 Definition of Periprosthetic Hip and Knee Infection provides evidence-based consensus criteria that help mitigate this challenge (Parvizi et al. 2018).

Management of PJI is similarly complex: patients face substantial morbidity and mortality, surgeons are limited by imperfect treatment options, and the healthcare system bears significant costs of care (Tande and Patel 2014; Okafor et al. 2023). The current standard of care combines at least six weeks of systemic intravenous and/or oral antibiotics with one of three operative strategies: debridement, antibiotics, and implant retention (DAIR); single-stage revision; or two-stage revision (Osmon et al. 2013).

While antibiotics are integral to PJI treatment, their clinical effectiveness remains limited largely because bacteria form biofilms on prosthetic surfaces and surrounding soft tissue, markedly diminishing systemic antimicrobial efficacy. Biofilms are complex extracellular polymeric matrices that encase microorganisms, conferring substantial protection against host defenses and antibiotics (Costerton et al. 1987). Bacteria within biofilms may exhibit up to several thousand-fold increases in antibiotic resistance compared with their planktonic counterparts (Ceri et al. 1999).

Biofilm in Periprosthetic Joint Infection

Bacterial biofilms were first observed in the 17th century by Antonie van Leeuwenhoek, who described aggregates of microorganisms adherent to surfaces. Biofilms are now understood as structured microbial communities embedded within a self-produced extracellular polymeric substance (EPS) matrix that, in vivo, preferentially adheres to nonviable tissue, necrotic debris, and foreign materials such as orthopedic implants (Chandki et al. 2011).

The modern concept of biofilm was formally established in the 1970s by J. William Costerton and colleagues, who demonstrated that bacteria predominantly exist in sessile, surface-associated communities rather than solely as free-floating (planktonic) organisms (Osmon et al. 2013; Costerton et al. 1978), a paradigm shift that fundamentally altered understanding of chronic and device-associated infections. The clinical implications for hip and knee arthroplasty were not fully appreciated until the 1990s, when accumulating evidence established biofilm formation as a central mechanism underlying PJI and confirmed that biofilm confers substantial resistance to both host immune responses and antimicrobial therapy (Costerton et al. 1978).

Biofilms are now recognized as a fundamental bacterial survival strategy responsible for up to 80% of chronic and device-related infections in humans (Khoury et al. 1992). Biofilm formation is an adaptive response to stressors such as nutrient limitation, desiccation, host immune pressure, and antimicrobial exposure, providing enhanced survival through collective protection, genetic exchange, and metabolic cooperation (Costerton et al. 1999). For pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa, biofilm formation facilitates persistence in host tissues and on medical devices, enabling long-term colonization despite therapeutic intervention (Donlan and Costerton 2002).

Biofilm development is a multistep process (Costerton et al. 1999; Hall-Stoodley et al. 2004) as shown in Fig. 1. Planktonic bacteria first attach reversibly via weak physicochemical interactions, then irreversibly via adhesins, pili, and exopolysaccharides. Microcolonies develop through proliferation and secretion of EPS (polysaccharides, proteins, lipids, extracellular DNA), eventually maturing into complex three-dimensional structures with water channels enabling nutrient flow and waste removal (Stoodley et al. 2002). Cells can then disperse and revert to a planktonic state, enabling colonization of new sites and perpetuating infection cycles (Rumbaugh and Sauer 2020; Hall and Mah 2017). These cycles are often reflected clinically in patients presenting with an abrupt, fulminant septic joint that, rather than representing new hematogenous seeding, instead reflects the acute manifestation of a previously indolent, chronic infection. Environmental factors such as pH and temperature influence biofilm formation and maturation (Y. H. Li et al. 2001; Stepanović et al. 2003), and once mature, biofilms become increasingly difficult to eradicate (Stoodley et al. 2002).

This difficulty stems from unique physiological properties: bacteria within a biofilm can exhibit a 1,000- to 8,000-fold increased tolerance to antibiotics compared with planktonic cells (Ceri et al. 1999; Nickel et al. 1985; Svensson Malchau et al. 2021), due to restricted antimicrobial penetration through the EPS matrix, altered microenvironments (hypoxia, nutrient gradients), and metabolically dormant “persister” cells (Lewis 2007). Biofilms also shield bacteria from phagocytosis and antibody binding (Stewart and Costerton 2001), explaining why biofilm-associated infections often become chronic and refractory to conventional treatment.

Limitations with Current Treatment Protocols: The Synovial Joint, MIC, MBEC, and the Biofilm Problem

The Synovial Joint

The human synovial joint is enclosed by a two-layered capsule that surrounds and protects the articular surfaces (Standring 2016). The outer fibrous capsule is composed of dense irregular connective tissue rich in type I collagen, arranged to resist multidirectional stress, providing mechanical stability, limiting excessive joint motion, and serving as an attachment site for ligaments and tendons; it is often continuous with the periosteum of adjacent bones (Standring 2016; Moore et al. 2018).

Deep to the fibrous capsule lies the synovial membrane, a thin, highly vascularized layer of loose connective tissue lining the joint capsule but not the articular cartilage or menisci (Moore et al. 2018). Its inner intimal layer (typically 1-4 cells thick) contains macrophage-like Type A synoviocytes, responsible for phagocytosis of debris and pathogens, and fibroblast-like Type B synoviocytes, which synthesize hyaluronic acid and lubricin (Moore et al. 2018). The subintimal layer beneath consists of loose connective tissue with a rich network of blood vessels, lymphatics, nerves, and adipocytes, facilitating nutrient exchange and dynamic regulation of the intraarticular environment (Smith 2011).

The synovial membrane serves several critical functions: producing lubricating, nutrient-supplying synovial fluid; acting as a semi-permeable barrier regulating exchange between the joint space and systemic circulation; and contributing to immune surveillance and clearance of pathogens and debris (Levick and McDonald 1995). These properties are directly relevant to PJI. The synovium is both a defensive interface, capable of immune surveillance and pathogen clearance, and a potential reservoir for infection, particularly with biofilm on adjacent implant surfaces. Its vascularity facilitates delivery of systemic antibiotics, but this may be insufficient to achieve concentrations necessary for biofilm eradication.

Systemic Antibiotic Penetration into the Joint: Pharmacokinetics and Limitations

The synovium is supplied by capillary networks from the systemic circulation, forming a semipermeable interface across which the intraarticular environment receives oxygen, nutrients, and antibiotics via passive diffusion and filtration (Simkin 1995). This arrangement inherently limits the intraarticular concentrations achievable with systemic therapy and may prevent levels required for effective biofilm eradication, as depicted in Fig. 2.

Penetration of systemic antibiotics into synovial fluid and cancellous bone has been evaluated for a wide range of agents (Thabit et al. 2019); in general, most antibiotics administered systemically can enter the synovial space, though at lower concentrations than corresponding plasma levels, reflecting passive diffusion and filtration across the synovial microvasculature.

Several pharmacokinetic studies have quantified synovial fluid-to-plasma concentration ratios. Boselli et al. demonstrated ratios of approximately 0.5 for piperacillin and 0.4 for tazobactam (Boselli et al. 2002), while Schwameis et al. reported a mean ratio for linezolid of 0.76±0.3431. Roy et al. reported a synovial fluid-to-serum ratio for vancomycin of approximately 0.3532. Yamada et al. demonstrated that cefazolin concentrations in cancellous bone reached only 19% of serum levels (Yamada et al. 2011), while aminoglycosides such as gentamicin and tobramycin demonstrated ratios ranging from 0.54 to 1.60, reflecting differences in dosing, sampling timing, and tissue characteristics (Dee and Kozin 1977). Taken together, these data show that while most systemic antibiotics enter the joint space, intraarticular concentrations are generally lower than systemic levels and highly variable; importantly, for many antibiotics, concentrations achieved in synovial fluid are sufficient to exceed the minimum inhibitory concentration (MIC) needed to treat planktonic bacteria (Levick and McDonald 1995).

However, these concentrations are often inadequate in PJI, where bacteria exist predominantly within biofilm; the extracellular polymeric matrix and altered bacterial metabolic state significantly impair antibiotic penetration and efficacy (Okae et al. 2022; Larsen and Fiehn 1996; Stewart 1996), requiring substantially higher concentrations for eradication compared with planktonic organisms (Larsen and Fiehn 1996; Stewart 1996). Experimental models demonstrate that the minimum biofilm eradication concentration (MBEC) may exceed these values by several orders of magnitude (Okae et al. 2022). Consequently, although systemic therapy may achieve intraarticular concentrations sufficient for planktonic killing, these levels are typically insufficient to eradicate biofilm-associated organisms—a pharmacokinetic and microbiologic mismatch that underscores the need for strategies achieving substantially higher, sustained local antibiotic concentrations.

Minimum Inhibitory Concentration (MIC) and Its Limitations in PJI

Systemic antibiotic dosing for PJI has historically been guided, and ultimately constrained, by the principle of targeting the minimum inhibitory concentration (MIC)—the lowest antimicrobial concentration required to inhibit visible growth after a standardized incubation period, typically 16-20 hours (Barnes et al. 2023). Since its introduction in the mid-20th century, MIC has served as the gold standard for antimicrobial susceptibility testing, guiding antibiotic selection and dosing through in vitro culture and assessment of growth inhibition across concentration ranges (Andrews 2001). This framework is highly effective for planktonic infections, allowing clinicians to tailor therapy for organisms such as MSSA and MRSA, but it does not account for the altered physiology, reduced metabolic activity, and protective extracellular matrix of biofilm-associated bacteria (Okae et al. 2022)—a critical gap given that PJI is fundamentally driven by biofilm formation on implant surfaces and surrounding tissue.

Studies comparing planktonic and biofilm-associated bacteria confirm that antibiotic concentrations required for biofilm eradication are substantially higher than MIC predicts (Okae et al. 2022; Brady et al. 2017), often by several orders of magnitude (Brady et al. 2017; Simões 2011; de Oliveira et al. 2016), due to impaired penetration, altered microenvironmental conditions, and persister cell populations (Stewart and Costerton 2001; Okae et al. 2022). Despite these limitations, systemic strategies for PJI remain largely MIC-based, contributing to the perception that antibiotics are ineffective against biofilm. However, this reflects a limitation of delivery rather than intrinsic drug failure: systemic antibiotics are constrained by both toxicity and the pharmacokinetics of joint penetration, often resulting in intraarticular concentrations below those needed for biofilm eradication.

Biofilm-associated bacteria are therefore not universally resistant to antibiotics, but require substantially higher concentrations for effective treatment. The challenge in PJI is one of inadequate drug delivery and concentration rather than antimicrobial inefficacy, reframing the problem from resistance to exposure—achieving sufficient local antibiotic levels within the joint. This concentration is defined as the minimum biofilm eradication concentration (MBEC).

Minimum Biofilm Eradication Concentration (MBEC)

MBEC is defined as the lowest antimicrobial concentration required to eradicate bacteria embedded within a biofilm, including metabolically inactive persister cells (Castaneda et al. 2016). Unlike MIC, which evaluates planktonic susceptibility, MBEC more accurately reflects conditions in biofilm-associated infections such as PJI. Its existence challenges the longstanding notion that antibiotics are intrinsically ineffective against biofilm, suggesting instead that eradication is possible but requires substantially higher concentrations than MIC predicts.

The concept of MBEC is far more recent than MIC, introduced by Ceri and colleagues in 1999 with the Calgary Biofilm Device (CBD), a standardized platform enabling reproducible biofilm formation on polystyrene pegs and direct comparison of MIC and MBEC for the same isolate (Ceri et al. 1999). The CBD and its derivatives remain widely used for high-throughput testing, exposing biofilms grown on microtiter pegs to antibiotic gradients and quantifying surviving bacteria after recovery (Ceri et al. 1999). While offering standardization and scalability, this system has important limitations, including abiotic surfaces, predominantly monospecies biofilms, and conditions that differ from the in vivo orthopedic environment. To address this, more clinically relevant models have been developed; for example, a rodent femoral implant model demonstrated biofilm formation directly on metallic implants in vivo, with MBEC estimation confirming that eradication thresholds substantially exceed MIC and may be even higher than on standard laboratory substrates (Yamada et al. 2011).

Across experimental systems, a consistent finding has emerged: antibiotic concentrations required to eradicate biofilm (MBEC) are orders of magnitude higher than those required to inhibit planktonic bacteria (MIC) (Okae et al. 2022; Brady et al. 2017; Simões 2011; de Oliveira et al. 2016; Castaneda et al. 2016). Cerca et al. demonstrated up to a 1,000-fold increase in antibiotic tolerance in biofilm-forming bacteria (Cerca et al. 2005), Brady et al. reported resistance patterns up to 1,000 times greater (Brady et al. 2017), and Svensson et al. observed increases exceeding 8,000-fold (Svensson Malchau et al. 2021). Additional studies show MBEC values frequently exceeding 2,000 µg/mL, far surpassing concentrations achievable with standard systemic dosing (Ando et al. 2024; Molina-Manso et al. 2013). Modeling of systemic versus supratherapeutic concentrations has demonstrated that systemic, MIC-based dosing is often insufficient to eradicate biofilm, while supratherapeutic concentrations approaching MBEC may be required for sterilization of implant-associated infections (Daffinee et al. 2023).

Emerging clinical data further support MBEC’s relevance. Li et al. evaluated patients with PJI treated with combined systemic and intraarticular (IA) therapy and demonstrated that IA administration achieved concentrations approximating MBEC, with successful infection control in all patients studied (M. Li et al. 2025), suggesting local delivery strategies may overcome the pharmacokinetic limitations of systemic therapy. Yao et al. demonstrated differences between MIC and MBEC for vancomycin and meropenem, with reductions in MBEC observed when combined with tranexamic acid, suggesting potential synergy (Yao et al. 2025), while Semeshchenko et al. found that among non-antibiotic agents, only certain ones, such as povidone-iodine and silver nitrate, achieved near-complete (>99.9%) biofilm eradication (Semeshchenko et al. 2025). Notably, Castaneda and colleagues demonstrated that for 11 of 12 antimicrobial-microorganism pairs tested, MBEC was lower after 5 days of antibiotic exposure than after 1 day, suggesting the concentration required for eradication may decrease with sustained exposure over time (Castaneda et al. 2016).

These findings support MBEC as a more appropriate framework than MIC for understanding and treating PJI. Importantly, MBEC does not imply antibiotics are ineffective against biofilm, but rather that effective treatment requires sufficiently high concentrations, adequate exposure time, and, in many cases, combination therapy. Clinically, this supports strategies aimed at increasing local antibiotic concentrations, prolonging exposure duration, and utilizing combination therapies to enhance biofilm penetration and target persister populations. Once standardized and validated, incorporation of MBEC into clinical decision-making has the potential to shift PJI treatment paradigms from MIC-based suppression toward concentration-driven biofilm eradication.

Historical Strategies to Achieve High Intraarticular Concentrations of Antibiotics

Local Antibiotic Delivery in PJI: Rationale and Limitations

Clinicians have long recognized that systemic antibiotic therapy often fails to achieve and sustain biofilm-eradicating concentrations at the site of infection, where organisms may require orders-of-magnitude higher concentrations than planktonic counterparts for clearance. As a result, multiple strategies have been developed to augment local antibiotic delivery while minimizing systemic toxicity, including antibiotic-impregnated polymethylmethacrylate (PMMA) cement spacers, antibiotic-loaded beads, intra-wound antibiotic powders, continuous local antibiotic perfusion (CLAP), continuous intraarticular catheter-based infusion, and emerging platforms such as hydrogels and biodegradable carriers (Matziolis et al. 2020; Pan et al. 2018; Abosala and Ali 2020; Capuano et al. 2018). While these modalities differ in delivery mechanism, they share a common objective: achieving and maintaining local concentrations that exceed the minimum biofilm eradication concentration (MBEC) for a duration sufficient to allow infection clearance (see Table 1).

A critical limitation of PMMA-based delivery is its non-sustained elution profile, characterized by an initial burst phase from rapid diffusion of surface-associated antibiotic, followed by a marked decline as elution becomes diffusion-limited within the cement matrix (Anagnostakos et al. 2009; van Vugt et al. 2019; Nelson et al. 1992). Anagnostakos et al. reported that peak concentrations occur within the first 24 hours, with antibiotic levels decreasing several-fold by approximately 5 to 7 days, a finding corroborated across multiple spacer and bead studies (Anagnostakos et al. 2009; van Vugt et al. 2019; Nelson et al. 1992); although these concentrations may remain above MIC thresholds, they are often insufficient relative to the substantially higher concentrations required for biofilm eradication (MBEC) (Osmon et al. 2013). Elution is strongly influenced by construct geometry: PMMA beads, with higher surface area-to-volume ratios than bulk spacers, demonstrate improved kinetics with higher peak concentrations and modestly prolonged release, though even in beads, release remains predominantly front-loaded with a rapid decline following the initial burst (Anagnostakos et al. 2009; van Vugt et al. 2019). This reflects PMMA’s mechanism as a delivery vehicle: antibiotics diffuse passively through a relatively dense, non-porous matrix, and once surface-accessible drug is depleted, the remaining drug becomes sequestered, resulting in progressively diminished elution (Anagnostakos et al. 2009; van Vugt et al. 2019; Nelson et al. 1992). Clinically, while early high concentrations may reduce initial bacterial load, the subsequent decline may permit persistence of biofilm-associated organisms, and PMMA constructs themselves may become substrates for biofilm formation once local concentrations fall below effective thresholds (Neut et al. 2005).

Intra-wound vancomycin powder has been explored both as a prophylactic measure in primary arthroplasty and as an adjunct in infection management, achieving very high local concentrations with minimal systemic absorption. Early retrospective studies suggested reduced surgical site infection and PJI rates; however, more recent randomized trials and higher-quality meta-analyses show inconsistent results, with several studies showing no significant reduction in infection rates and a potential increase in aseptic wound complications such as persistent drainage, leaving its routine use in primary arthroplasty controversial (Nelson et al. 1992). In established PJI, vancomycin powder has been used adjunctively with DAIR or revision arthroplasty, though literature on this use is scant; it can provide supratherapeutic local concentrations exceeding those achievable systemically, but lacks sustained elution, with rapid dissipation over hours to days, limiting its effectiveness as a standalone modality for eradicating mature biofilm.

In summary, while antibiotic-loaded PMMA spacers and beads and antibiotic powders achieve very high local concentrations, their rapid early peak followed by substantial decline means they may not consistently maintain concentrations above MBEC thresholds for the duration required for eradication, highlighting a critical limitation of current local delivery strategies for PJI.

Intraoperative Irrigation: Efficacy and Limitations in Biofilm Eradication

Although not a sustained delivery strategy, intraoperative chemical irrigation is an adjunctive technique intended to reduce bacterial burden and disrupt biofilm at the time of surgery, though debate continues regarding the optimal solution. Investigated agents include chlorhexidine, povidone-iodine, sodium hypochlorite, hydrogen peroxide-based combinations, acetic acid-containing solutions, and antibiotic-containing lavage, which differ substantially in antimicrobial spectrum, mechanism, cytotoxicity, and ability to penetrate biofilm. Schmidt et al. evaluated several irrigation solutions and found chlorhexidine and povidone-iodine the most effective at eradicating bacterial contamination in vitro, outperforming sodium hypochlorite and antibiotic-containing solutions (Schmidt et al. 2018), consistent with broader literature suggesting membrane-disrupting antiseptics may be more effective than dilute antibiotic solutions for rapidly reducing bacterial load. Similarly, Hamad et al. found that povidone-iodine combined with hydrogen peroxide demonstrated the greatest bactericidal activity, followed by acetic acid-based solutions (Hamad et al. 2025), supporting the concept that combining agents with complementary mechanisms—such as oxidative damage and membrane disruption—may enhance efficacy.

Despite these encouraging in vitro results, several limitations must be emphasized. Most studies are performed under controlled laboratory conditions that may not replicate the complex environment of an infected joint, where bacteria are embedded within mature biofilm on implant surfaces and devitalized tissue, and the brief exposure times typical of intraoperative irrigation are likely insufficient for true eradication. Irrigation is also inherently transient: even highly effective solutions provide exposure limited to minutes during surgery, after which no sustained antimicrobial activity remains—a fundamental mismatch with the prolonged exposure biofilm eradication requires. Additionally, increasing antiseptic concentration to improve efficacy is constrained by cytotoxicity to host tissues, including chondrocytes, fibroblasts, and osteoblasts, particularly relevant in joint-preserving procedures such as DAIR, limiting the ability to escalate dosing to levels that may be required for biofilm eradication (Caid et al. 2022).

In this context, intraoperative irrigation shares a key limitation with antibiotic-loaded PMMA: while it may contribute to initial bacterial clearance, it does not provide the sustained antimicrobial exposure necessary to reliably eradicate biofilm, further underscoring the rationale for adjunctive strategies, such as intraarticular antibiotic infusion, that maintain high local concentrations over time and better align with the biological requirements of infection eradication.

The Future: Intra-articular Antibiotic Infusion

Effective treatment of PJI requires not only achieving, but sustaining, antibiotic concentrations at or above MBEC within the joint space—a threshold existing strategies, limited by transient or declining local concentrations, fail to maintain over time. Consequently, sustained intraarticular antibiotic delivery has emerged as a logical and necessary strategy to overcome this pharmacokinetic limitation.

One approach is continuous intraarticular (IA) antibiotic infusion. The literature on IA delivery has expanded meaningfully over the past decade, now including pharmacokinetic studies demonstrating achievable intraarticular concentrations, retrospective clinical series reporting favorable outcomes, and recent focused reviews supporting its potential role in managing biofilm-associated infection. Collectively, these studies support a consistent central concept: direct IA delivery can achieve synovial concentrations far higher than those attainable with systemic therapy alone, while generally maintaining comparatively modest serum exposure. Reported infection-control rates have been encouraging across cohorts treated with DAIR, single-stage revision, and salvage-type scenarios after prior failed surgery. At the same time, available evidence remains dominated by retrospective case series from a small number of centers, with substantial heterogeneity in surgical indications, antibiotic protocols, catheter techniques, and outcome definitions.

Pharmacokinetic Foundation

The mechanistic rationale for IA infusion is strongest in the pharmacokinetic literature. Roy et al. directly compared vancomycin delivered into the knee joint versus standard intravenous administration and found that daily IA injection achieved and maintained vastly superior, sustained therapeutic synovial concentrations throughout the dosing interval, whereas IV administration delivered much lower joint levels (Roy et al. 2014), demonstrating the central pharmacologic advantage of IA therapy: bypassing the vascular limitations of the infected periprosthetic environment to deliver drug directly to the site of biofilm burden. Whiteside, Roy, and Nayfeh later reported a mean synovial vancomycin peak concentration of 9,242 µg/mL among 11 patients treated with IA delivery, while serum trough levels ranged from 4.2 to 25.2 µg/mL with a mean of 12.3 µg/mL, approximately 9.6% of the joint trough value (Whiteside and Roy 2017)—striking findings showing the ability to maintain extraordinarily high intraarticular exposure while keeping systemic levels monitorable and clinically manageable.

Growing clinical literature supports IA infusion’s feasibility and efficacy. Early work by Antony et al. demonstrated infection-free survival in approximately 88-89% of patients treated with aggressive debridement, single-stage revision, and IA antibiotic administration, with minimal systemic toxicity (Antony et al. 2015). Whiteside and colleagues further reported 95% infection eradication in both hip and knee arthroplasty using catheter-based IA infusion protocols (Whiteside and Roy 2017; Whiteside et al. 2016). More recent studies have validated these findings across different populations and surgical strategies: Ji et al. reported favorable outcomes using IA infusion in single-stage revision for culture-negative PJI (Ji et al. 2020), Zou et al. confirmed the ability to achieve sustained intraarticular concentrations of vancomycin and meropenem over time (Zou et al. 2024), and Vandeputte et al. reported a 100% success rate treating 18 infected THAs with single-stage revision combined with IA infusion (Vandeputte et al. 2025). In a 2022 series of 78 patients with PJI after multiple prior failed surgeries—including failed DAIRs, failed resections, failed two-stage revisions, polymicrobial infections, and even fungal infections—Ji and colleagues reported an 87% success rate at a mean of 85 months, concluding that IA administration may be a viable option even in difficult salvage scenarios characterized by poor vascularity and established biofilm (Ji et al. 2022).

Jarusriwanna, Mu, and Parvizi’s 2024 review of IA infusion following THA concluded that adjunctive local antibiotic infusion after surgical treatment of hip PJI is associated with high success rates and low systemic complication rates, while emphasizing the need for higher-quality comparative trials; their review summarized success rates of approximately 90% to 100% with DAIR, 82% to 100% with single-stage revision, and around 80% with two-stage revision in the available hip literature (Jarusriwanna et al. 2024).

Although not identical to classic Hickman-catheter IA protocols used in some hip and knee series, the broader literature on continuous local antibiotic perfusion (CLAP) is conceptually aligned and deserves mention. Miyake and Takagi reported on eight patients with PJI (hips and knees, with both DAIR and two-stage revision represented) treated with CLAP for a mean duration of 8.5 days; all eight achieved infection resolution without recurrence at last follow-up, with no systemic gentamicin toxicity or CLAP-related complications observed (Miyake and Takagi 2024). While small, this study supports the broader premise that continuous local delivery can be safely combined with standard surgical treatment.

The Development Horizon

Growing understanding of MBEC has motivated industry development of novel products addressing the biofilm problem in PJI. Osteal Therapeutics is developing a continuous irrigation system that cycles between vancomycin and tobramycin over a 7-day, in-hospital treatment period to achieve supra-MBEC synovial concentrations for two-stage revision in hips and knees; although not yet FDA-approved, it has shown clinical proof-of-concept and received Orphan Drug and Qualified Infectious Disease Product (QIDP) designations. ForCast Orthopedics is developing a proprietary system using an indwelling catheter, ambulatory pump, and prefilled syringes for daily bolus dosing over 3-6 weeks in an at-home treatment following DAIR or revision in any joint, also achieving supra-MBEC concentrations; it has demonstrated preclinical proof-of-concept and received the same FDA designations, but is also not yet approved.

Alternate approaches are also in development. Peptilogics is developing a new antibiotic that specifically targets biofilm as a one-time treatment at the time of DAIR or revision, currently being evaluated in clinical trials. Garwood Medical and Solenic Medical have each developed non-invasive approaches using magnetic fields to eliminate biofilm—inducing localized chemical reduction and localized heating, respectively—both reporting success in preclinical studies. The breadth of approaches in development highlights the criticality of this unmet medical need.

Discussion

Taken together, the studies to date suggest that IA antibiotic infusion is best viewed as a promising adjunctive delivery strategy rather than a standalone treatment. Its major strength is pharmacologic: it can reliably create synovial concentrations dramatically higher than those achieved through IV therapy and plausibly closer to concentrations required for biofilm suppression or eradication. Its clinical literature, though still limited, is increasingly consistent in showing encouraging infection-control rates across a range of applications, including DAIR, single-stage revision, culture-negative PJI, salvage after multiple failed procedures, and infected cementless THA. The published IA infusion literature now supports three defensible conclusions: first, IA delivery is pharmacokinetically superior to IV therapy for producing high joint-space antibiotic concentrations; second, available clinical series suggest it can be used safely and effectively as an adjunct in selected patients with PJI; and third, despite these encouraging results, the field still lacks the comparative evidence needed to define which patients benefit most, which antibiotics and dosing schedules are optimal, and whether IA infusion truly improves outcomes over modern systemic therapy and contemporary revision protocols alone.