Antimicrobial peptides occur naturally in our intrinsic immune system. PLG0206 is a novel, engineered, 24-amino acid peptide which has broad-spectrum antimicrobial activity, including in biofilm and against multi-drug resistant pathogens (1,2). This is the first clinical study to evaluate the safety and tolerability of PLG0206 when administered via an irrigation solution in patients with periprosthetic joint infections (PJI) following total knee arthroplasty (TKA) during debridement, antibiotics, and implant retention (DAIR). Secondary objectives were to evaluate pharmacokinetics (PK), biomarkers and initial clinical efficacy at one year post-DAIR procedure. This prospective, multicenter, open-label, interventional study assessed two dose levels of PLG0206. Fourteen patients underwent revision for PJI after TKA. At the end of debridement, they received a single intra-articular irrigation of PLG0206 into the wound cavity lasting 15 minutes at concentrations of 3 mg/mL (n=7) or 10 mg/mL (n=7). Patients received post-operative care and intravenous/oral antimicrobial therapy as per their institutional guidelines. Patients were monitored for safety and signs of relapse or persistent infection for 12 months post study drug administration and PK and blood biomarkers were assessed.Aim
Method
Several options to standardize the definition of periprosthetic joint infection (PJI) have been created including the 2013 Musculoskeletal Infection Society (MSIS), 2018 Intentional Consensus Meeting (ICM), and the 2019 proposed European Bone and Joint Infection Society (EBJIS) criteria. Synovial fluid biomarkers have been investigated in an effort to simplify and improve the diagnosis of PJI. The aim of this study was to test the sensitivity, specificity, positive, and negative predicted values (PPV and NPV, respectively) of a calprotectin point of care (POC) test for diagnosing PJI in revision total knee arthroplasty (TKA) patients comparing different sets of criteria (2013 MSIS, 2018 ICM, and 2019 EBJIS criteria) used to define patients as with or without infection. From October 2018 to January 2020 and under IRB approval 123 intraoperative samples of synovial fluid were prospectively collected at two academic hospitals in the same institution from revision TKA patients. All patients underwent standard clinical and laboratory evaluation for PJI at our institution, allowing for categorization using the 3 criteria. Patients were adjudicated by 2 blinded and independent reviewers for the 3 sets of criteria. The 3 criteria agreed 91.8% of the time. Four likely cases by the 2019 proposed EBJIS were considered unlikely and 1 inconclusive case by the 2018 ICM was considered not infected for the purposes of analysis. Calprotectin POC testing followed manufacturer's instructions using a threshold of >50 mg/L to indicate PJI. Sensitivities, specificities, PPV, NPV, and areas under the curve (AUC) were calculated for the 3 sets of criteria.Aim
Method
Periprosthetic joint infection (PJI) is a devastating complication of total joint arthroplasty. While research has focused on developing better tests for disease diagnosis, treatment options have stayed relatively constant over the years with high failure rates ranging from 30%–50% and are due in part to the protective biofilm produced by some bacterial species. Current treatment options are compromised by the presence of biofilm, emphasizing the need for novel treatment strategies to be developed. Our group has developed a novel treatment (PhotothermAA) which has demonstrated Rabbits were fitted with a titanium implant into the tibial plateau and inoculated with 5×106 CFU Xen36 (luminescent Aim
Method
Despite several synovial fluid biomarkers for diagnosis of periprosthetic joint infection (PJI) have being investigated, point-of-care (POC) tests using these biomarkers are not widely available. Synovial calprotectin has recently been reported to effectively exclude diagnosis of PJI and a novel lateral flow POC test using it has shown potential to be effective. Thus, the aims of this study were to 1) validate calprotectin POC with enzyme linked immunosorbet assay (ELISA) 2) at 2 separate thresholds for PJI diagnosis in total knee arthroplasty (TKA) patients using the 2013 Musculoskeletal Infection Society (MSIS) PJI diagnosis criteria as the gold standard. Intraoperative synovial fluid samples were prospectively collected from 123 patients who underwent revision TKAs (rTKA) at two academic hospitals within the same healthcare system from October 2018 to January 2020. The study was conducted under IRB approval. Included patients followed the hospital standard for their PJI diagnostic work-up. Data collection included demographic, clinical, and laboratory data in compliance with MSIS criteria. Synovial fluid samples were analysed by calprotectin POC and ELISA tests in accordance with manufacturer's instructions. Patients were categorized as septic or aseptic using MSIS criteria by two independent reviewers blinded to calprotectin assay results. The calprotectin POC and ELISA test performance characteristics were calculated with sensitivities, specificities, positive, and negative predicted values (PPV and NPV, respectively) and areas under the curve (AUC) for 2 different PJI diagnosis scenarios: (1) a threshold of >50 mg/L and (2) a threshold of >14 mg/L.Aim
Method
