Rethinking How We Define and Treat Periprosthetic Joint Infection

Commentary Periprosthetic joint infection (PJI) remains a daunting complication in orthopaedics, with major implications for patients and health-care systems1,2. Traditional definitions and treatment paradigms have guided management strategies for decades. However, emerging data suggest that these frameworks may no longer be sufficient to address the nuanced distinctions between acute and chronic PJI as well as the biological complexities underlying these infections. As a field, we may be facing the necessity for a paradigm shift in how we define and treat PJI, particularly in light of advancements in understanding host-microbe interactions and innovations in treatment strategies. The distinction between acute and chronic PJI has historically relied on time-based definitions—typically 4 to 6 weeks post-arthroplasty and/or symptoms. However, as the article by Dr. Parvizi highlights, infections exist on a continuum rather than as discrete entities, complicating rigid categorizations. Acute infections are often characterized by planktonic bacterial forms that elicit robust immune responses, whereas chronic infections are dominated by biofilm-associated bacteria that evade both the immune system and antibiotics. This biological divergence necessitates tailored treatment strategies, as one-size-fits-all approaches are insufficient. For instance, acute PJI may benefit from aggressive surgical debridement and systemic antibiotics, while chronic PJI may require innovative antibiofilm agents or implant removal methods such as 1-stage or 2-stage exchange arthroplasty3. Two-stage exchange arthroplasty has long been the gold standard for chronic PJI4. However, recent evidence, including findings from the INFORM trial, suggests comparable outcomes with 1-stage procedures for selected patient populations5. Two-stage exchanges carry notable drawbacks, including prolonged disability, increased health-care costs, and higher mortality rates between stages. Furthermore, as Dr. Parvizi notes, the lack of clear metrics for the optimal timing of reimplantation exacerbates the risk of treatment failure. These challenges highlight the urgency of exploring alternative strategies that integrate emerging technologies and multidisciplinary insights. One-stage exchange may address some of these challenges but carries limitations, such as logistical and technical complexity, contested narrow indications with debates over the procedure’s broader applicability, a persistent risk of reinfection without the opportunity for reassessment, and barriers including insufficient reimbursement and health-care system support. More importantly, beyond the debate between 1-stage, 1.5-stage, or 2-stage procedures, there remain critical gaps in our understanding. For example, the immune system plays a pivotal yet underappreciated role in PJI pathogenesis6. Neutrophils and macrophages are critical in early infection control but are often rendered ineffective against biofilm-embedded bacteria. Biofilms not only act as physical barriers but also modulate immune responses, promoting anti-inflammatory phenotypes and evading effector functions (the immune system’s mechanisms to neutralize pathogens). Understanding these immune dynamics could pave the way for novel therapeutic approaches, such as immunomodulatory treatments to enhance host defenses or preoperative immune profiling to identify at-risk patients6. Given these complexities, redefining PJI management must encompass both diagnostic and therapeutic dimensions: Refined definitions. Time-based distinctions should be complemented by biomarkers that reflect the biological state of the infection as adjuncts to traditional criteria. Personalized treatments. Tailoring interventions on the basis of infection type (acute versus chronic), immune status, and microbial characteristics may improve outcomes. Innovative therapies. Embracing advancements in debridement, local antibiotic delivery systems, antibiofilm agents, and adjuvant therapies may offer the potential to overcome current limitations. “One-stage” protocols. Expanding indications for 1-stage or abbreviated 2-stage exchange, coupled with rigorous clinical trials, may reduce patient morbidity without compromising efficacy. The management of PJI must evolve to reflect the growing body of evidence of its biological intricacies and clinical challenges. By rethinking how we define and approach PJI, we may unlock new strategies that not only enhance treatment outcomes but also improve patients’ quality of life. This will require collaboration across disciplines, investment in innovative research, and a willingness to challenge entrenched practices. As Dr. Parvizi aptly notes, our patients deserve better—they deserve a care paradigm that addresses the full spectrum of PJI complexities.