Background Although recent guidance recommends early surgical debridement for native joint septic arthritis (NJSA), supporting data, particularly on long-term outcomes, remains scarce. Methods We conducted a retrospective multicenter cohort study of adults (≥18 years) with NJSA who underwent surgery across Mayo Clinic campuses between 2012 and 2021. Clinical outcomes at 1 year were assessed using a 9-level Desirability of Outcome Ranking (DOOR) scale, incorporating survival, treatment failure (relapse, reinfection, readmission, or significant surgical events), and joint recovery. Time to surgery from hospital admission was analyzed both as a continuous variable and as categories: <1, 1–2, or ≥3 days. Results Among 268 patients, 30% underwent surgery <1 day from admission, 47% in 1–2 days, and 24% in ≥3 days. At 1 year, 57% achieved full recovery without unfavorable events (DOOR score 1), while treatment failure occurred in 34%. In unadjusted analyses, longer surgical delay was significantly associated with higher (worse) DOOR scores (per IQR increase [from 0 to 2 days], OR: 1.5; 95% CI: 1.0–2.1; p = 0.026), increased 1-year mortality (HR: 1.7; 95% CI: 1.1–2.6; p = 0.019) and treatment failure (HR: 1.5; 95% CI: 1.1–2.0; p = 0.007). Even after adjusting for age and Charlson comorbidity index, the association between surgical delay and treatment failure remained significant (HR: 1.5; 95% CI, 1.1–2.0; p=0.016). Conclusion The finding that delayed surgical intervention is associated with an increased risk of treatment failure reinforces current expert recommendations for timely surgical management in NJSA.

It has been shown that the outcome of a DAIR (debridement, antimicrobial therapy, and implant retention) procedure depends on multiple factors (e.g. infection type, host factors, clinical presentation, condition of surrounding soft tissue, causing pathogen, surgical technique, antimicrobial therapy); therefore, adequate patient selection is key for DAIR success. In this position paper, we discuss the most relevant factors influencing the outcome and define indications, contraindications, and risk factors for a DAIR procedure based on the most robust and most recently published data. Furthermore, we discuss the surgical technique in combination with systemic antimicrobial therapy in patients undergoing a DAIR procedure. This position paper may help reduce reinfection rates as well as the physical, psychological, and economic burden associated with periprosthetic joint infection (PJI). We believe that a reasonable outcome can be achieved with careful patient selection, a dedicated multidisciplinary team, and an appropriate surgical technique and antimicrobial therapy.

Aims: It remains unclear if postoperative antibiotic (AB) treatment is advantageous in presumed aseptic revision arthroplasties of the hip (rTHA) and knee (rTKA) with unexpected positive intraoperative cultures (UPIC). The aim of this study is to evaluate if there is a difference in the re-revision rate in patients with UPIC when treated with postoperative AB or when postoperative AB is withheld. Methods: In this retrospective matched cohort study we compared the re-revision rates in rTHA and rTKA with (AB group: 45 rTHA, 25 rTKA) and without (non-AB group: 45 rTHA, 25 rTKA) AB treatment in patients with UPIC. Baseline covariates for matching were the microorganism (likely or not likely to be a contaminant), patient demographics, joint, revision type, surgical site infection score, American Society of Anesthesiologists classification, serum C-reactive protein (CRP). Results: After a median follow-up of 4.1 (inter-quartile range, IQR: 2.9–5.5) years after rTHA and rTKA, the re-revision rate between the AB group and the non-AB group was 14.3 % versus 15.7 % (P=0.81). In the AB group, 4.3 % (3/70) of patients underwent revision due to septic complications compared to 5.7 % (4/70) in the non-AB group (P=0.69). None of the patients were diagnosed with a confirmed periprosthetic joint infection (PJI) according to the PJI diagnostic criteria of European Bone and Joint Infection Society (EBJIS). In 22/70 (31.4 %) of the patients in the AB group and in 15/70 (21.4 %) of the patients in the non-AB group, a diagnosis of “infection likely” was made according to the EBJIS criteria (P=0.18). All UPICs with low virulent microorganisms were considered to be contamination (coagulase-negative Staphylococci; Corynebacterium; anaerobic Gram-positive bacilli and cocci, e.g., Finegoldia magna, Cutibacterium acnes). Conclusion: Postoperative AB treatment did not result in a decreased re-revision rate in patients with UPIC in presumed aseptic rTHA and rTKA. Patients diagnosed with pathogens classified as a likely contaminant can be safely ignored.

Importance Fracture-related infection (FRI) is a serious complication following fracture fixation surgery. Current treatment of FRIs entails debridement and 6 weeks of intravenous (IV) antibiotics. Lab data and retrospective clinical studies support use of oral antibiotics, which are less expensive and may have fewer complications than IV antibiotics. Objective To evaluate the effectiveness of treatment of FRI with oral vs IV antibiotics. Design, Setting, and Participants The POvIV multicenter, prospective randomized clinical trial was conducted across 24 trauma centers in the US among patients aged 18 to 84 years who had fracture repair or arthrodesis with fixation with implants and developed an FRI without radiographic evidence of osteomyelitis. Patients were enrolled between March 2013 and September 2018 and followed up for 12 months after hospitalization for treatment of their FRI. Intervention Oral vs IV antibiotics following FRI. Main Outcomes and Measures The primary outcome was number of surgical interventions, and the primary hypothesis was noninferiority of oral vs IV antibiotics with respect to the number of study injury–related surgical interventions by 1 year. Unadjusted modified intent-to-treat (mITT) and adjusted per-protocol (PP) analyses were prespecified. A post hoc adjusted mITT analysis was conducted to resolve discrepancies between the results of the prespecified mITT and PP analyses. Recurrence of a deep surgical site infection was a key secondary outcome. Results Among 233 total patients, mean (SD) age was 46.0 (13.9) years, and 53 patients were female (22.7%). The mean number of surgical interventions within 1 year was 1.3 and 1.1 for the oral and IV groups, respectively. The upper bound of the 95% confidence interval of the mean difference with unadjusted mITT analysis was 0.59, which was lower than the prespecified noninferiority margin of 0.67, indicating noninferiority of oral to IV antibiotics. Adjusted PP analysis did not support noninferiority of the number of reoperations. A post hoc adjusted mITT analysis also showed noninferiority. The treatment effects estimates for the key secondary outcome of reinfection showed a similar pattern as those for the primary outcome. Conclusions and Relevance In this prospective randomized clinical trial, oral antibiotic treatment was noninferior to IV treatment with respect to the primary outcome of number of surgical interventions based on mITT analysis. However, there is some uncertainty in these findings based on preplanned and post hoc secondary analyses. A similar pattern of treatment effect estimates was observed for the secondary outcome of recurrence of infection.

Introduction There have been conflicting reports on the risk of periprosthetic joint infection (PJI) with the use of alternative antibiotics to cefazolin following arthroplasty. We leveraged recent data from a nationally representative multi-payer dataset to investigate this question. Methods We queried a healthcare dataset from 2016 to 2022 to identify primary total hip arthroplasties (THAs) using Current Procedural Terminology (CPT) and International Classification of Disease-Procedure Coding System (ICD-PCS) codes (27130, 0SR90xx, 0SRB0xx) with a corresponding osteoarthritis diagnosis (International Classification of Disease-Clinical Modification (ICD-CM): M16). Patient demographics, characteristics, and outcomes were extracted from existing dataset variables. The PJIs were defined using ICD-10 diagnosis codes from the Centers for Medicare & Medicaid Services’ procedure-specific complication measure within 90 days of surgery. We compared PJI between patients receiving cefazolin antibiotic prophylaxis and patients who received an alternative antibiotic or cefazolin plus another antibiotic. The association between cefazolin use and PJI was evaluated using multinomial logistic regression. This study included 289,369 primary THA patients from 2016 to 2022. There were 25,164 patients (8.7%) who received a non-cefazolin antibiotic, 200,367 (69.2%) received cefazolin only, and 63,838 (22.1%) received cefazolin plus an alternative antibiotic. Results In univariate analysis, there was a significant difference in the rate of 90-day PJI between the non-cefazolin group, cefazolin only, and cefazolin plus other antibiotic group (0.9, 0.5, and 0.5%, respectively, P < 0.001). In a logistic regression analysis that adjusted for age, sex, payer, race, ethnicity, and Elixhauser Comorbidity Index, the use of cefazolin only and cefazolin plus other antibiotic, were associated with reduced risk of 90-day PJI [OR (odds ratio) 0.62, 95% CI (confidence interval) (0.53 to 0.72), P < 0.001] and [OR 0.64, 95% CI (0.54 to 0.76), P < 0.001]. Conclusions In this nationally representative multi-payer study using recent data, patients who received antibiotic prophylaxis with cefazolin had lower 90-day rates of PJI compared to those receiving alternative antibiotics during primary total hip arthroplasty.

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.