Background This study aimed to identify the success rate of debridement, antibiotics, and implant retention (DAIR) for prosthetic joint infection (PJI) in a large prospective cohort of patients undergoing total knee arthroplasty (TKA). The ability for different PJI classification systems to predict success was assessed. Methods Prospective data recorded in the Prosthetic Joint Infection in Australia and New Zealand Observational study were analyzed. One hundred eighty-nine newly diagnosed knee PJIs were managed with DAIR between July 2014 and December 2017. Patients were prospectively followed up for 2 years. A strict definition of success was used, requiring the patient being alive with documented absence of infection, no ongoing antibiotics and the index prosthesis in place. Success was compared against the Coventry (early PJI ≤1 month), International Consensus Meeting (early ≤90 days), Auckland (early <1 year), and Tsukayama (early ≤1 month, hematogenous >1 month with <7 days symptoms, chronic >1 month with >7 days symptoms) classifications. Results DAIR success was 45% (85/189) and was highest in early PJIs defined according to the Coventry (adjusted odds ratio [aOR] = 3.9, P = .01), the International Consensus Meeting (aOR = 3.1, P = .01), and the Auckland classifications (aOR = 2.6, P = .01). Success was lower in both hematogenous (aOR = 0.4, P = .03) and chronic infections (aOR = 0.1, P = .003). Conclusion Time since primary TKA is an important predictor of DAIR success. Success was highest in infections occurring <1 month of the primary TKA and progressively decreased as time since the primary TKA increased.

ABSTRACT Prosthetic joint infections (PJI) remain among the most devastating complications in orthopedic surgery, with increasing incidence paralleling the growth in arthroplasty procedures worldwide. While treatment protocols are well-established, evidence supporting current approaches is lacking, and outcomes remain suboptimal, highlighting the need for improved therapeutic strategies. The objective of this study is to review ongoing and recently completed randomized controlled trials (RCTs) investigating novel approaches to PJI prevention and treatment. We searched PubMed and ClinicalTrials.gov databases for RCTs that focused on PJI management, and that are ongoing or completed within the 6 months preceding February 28, 2025. We included investigator-initiated trials, studies of novel therapeutic agents, and studies on infection prevention strategies. We extracted and reviewed data regarding trial design, interventions, and outcomes. We identified significant advances in three key areas: (i) investigator-initiated trials exploring optimization of current surgical and antimicrobial treatment strategies, including the ROADMAP adaptive platform trial (ii); novel therapeutic agents, including engineered antibacterial peptides, monoclonal antibodies, and new-generation antibiotics specifically targeting biofilm-associated infections; and (iii) prevention strategies, particularly focusing on perioperative antibiotic protocols. Recent trials demonstrate promising approaches to reducing antibiotic exposure while maintaining efficacy, novel mechanisms for biofilm disruption, and strategies for optimizing perioperative prophylaxis. Investigator-initiated trials like ROADMAP and SOLARIO are challenging traditional paradigms, particularly in antibiotic duration, while novel therapeutics targeting biofilm through various mechanisms show promise in early-phase trials. Future research should prioritize cost-effectiveness analyses, targeted studies for specific patient subgroups, and evaluation of combination therapeutic approaches.

Introduction: Culture-negative (CN) prosthetic joint infections (PJIs) account for approximately 10 % of all PJIs and present significant challenges for clinicians. We aimed to explore the significance of CN PJIs within a large prospective cohort study, comparing their characteristics and outcomes with culture-positive (CP) cases. Methods: The Prosthetic joint Infection in Australia and New Zealand Observational (PIANO) study is a prospective, multicentre observational cohort study that was conducted at 27 hospitals between 2014 and 2017. We compared baseline characteristics and outcomes of all patients with CN PJI from the PIANO cohort with those of CP cases. We report on PJI diagnostic criteria in the CN cohort and apply internationally recognized PJI diagnostic guidelines to determine optimal CN PJI detection methods. Results: Of the 650 patients with 24-month outcome data available, 55 (8.5 %) were CN and 595 were CP. Compared with the CP cohort, CN patients were more likely to be female (32 (58.2 %) vs. 245 (41.2 %); p = 0.016), involve the shoulder joint (5 (9.1 %) vs. 16 (2.7 %); p = 0.026), and have a lower mean C-reactive protein (142 mg L−1 vs. 187 mg L−1; p = 0.016). Overall, outcomes were superior in CN patients, with culture negativity an independent predictor of treatment success at 24 months (adjusted odds ratio, aOR, of 3.78 and 95 %CI of 1.65–8.67). Suboptimal diagnostic sampling was common in both cohorts, with CN PJI case detection enhanced using the Infectious Diseases Society of America PJI diagnostic guidelines. Conclusions: Current PJI diagnostic guidelines vary substantially in their ability to detect CN PJI, with comprehensive diagnostic sampling necessary to achieve diagnostic certainty. Definitive surgical management strategies should be determined by careful assessment of infection type, rather than by culture status alone.

Background Peri-prosthetic joint infection (PJI) is a devastating complication of joint replacement surgery. Determining the optimal duration of intravenous (IV) antibiotics for PJI managed with debridement and implant retention (DAIR) is a research priority. Methods Patients undergoing DAIR for early and late-acute PJI of the hip or knee were randomised to receive 2 (short-course) or 6 (standard-course) weeks of IV antibiotics, with both groups completing 12 weeks of antibiotics in total. The primary endpoint of this pilot, open-label, randomised trial was a 7-point ordinal desirability of outcome ranking (DOOR) score, which accounted for mortality, clinical cure and treatment adverse events at 12 months. Duration of IV treatment was used as a tiebreaker, with shorter courses ranked higher. Outcome adjudication was performed by expert clinicians blinded to the allocated intervention (Australia and New Zealand Clinical Trials Registry ACTRN12617000127303). Results 60 patients were recruited; 31 and 29 were allocated to short- and standard-course treatment, respectively. All had an evaluable outcome at 12 months and were analysed by intention-to-treat. Clinical cure was demonstrated in 44 (73%) overall; 22 (71%) in the short-course group and 22 (76%) in the standard-care group (P=0.77). Using the DOOR approach, the probability that short- was better than standard-course treatment was 59.7% (95% confidence interval 45.1-74.3). Conclusions In selected patients with early and late-acute PJI managed with DAIR, shorter courses of IV antibiotics may be appropriate. Due to small sample size, these data accord with, but do not confirm, results from other international trials of early transition to oral antibiotics.