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
Acute postoperative periprosthetic joint infection (PJI) is a serious complication after any hemiarthroplasty (HHA) implanted due to a proximal hip fracture. The growing number of chronic institutionalized geriatric patients (CIGP) colonized with multi-drug resistant bacteria (e.g.: MRSA), not covered by usual antibiotic prophylaxis, has been identified as a risk factor for PJI after HHA. We therefore sought to compare the HHA infection characteristics between non-institutionalized patients (NIP) with proximal hip fractures and CIGP. We investigate (1) the rate of compliance with a new proposed protocol, (2) the acute infection rate, 3) the microbiologic characteristics of the infection, and 4) the success of the new protocol. We gathered clinical, operative and infection data on all patients who underwent HHA due to a proximal femoral fracture in our center, during a 3-year period. We focus in the cases of acute postoperative infection (Zimmerli´s criteria). The new proposed antibiotic prophylaxis is cefazolin except in CIGP in which co-trimoxazole is used. During the study period a total of 385 HHA in 385 patients were performed. In all cases the HHA was performed after a proximal femoral fracture. Overall, 109 patients (28,2%) were CIGP. We found an acute postoperative PJI in 21 out 385 HHA procedures, that is, a global acute infection rate of 5.43%. Ten out 109 (9.17%) CIGP patients resulted infected compared to 11 out 278 (3.9%) non-institutionalized patients (p: 0.049). One or more causative microorganisms were identified in 20/21 (95%) of PJI. Globally the Gram-Negative bacilli group accounted for the majority of the infections (60%). Staphylococus aureus was isolated in 3 cases (8.6%) with only a single MRSA infection. The percentage of polymicrobial infections was 47% (10 out of 21). Co-trimoxazole was used in the prophylaxis in 80.1% of the CIGP. In the infected cases a non-effective drug against the microorganism was used in the prophylaxis in 17 (81%) of the acute infected HHA. We confirm that institutionalized patients are more prone to acute infections after a HHA. Our current strategy of antibiotic prophylaxis has showed to be effective in preventing MRSA PJI in CIGP. However, we found an increased rate of infection due to gram-negative bacilli non-covered by the current antibiotic prophylaxis. According our data an extended antibiotic prophylaxis on gram-negative drug will be proposed to be implemented in CIGP scheduled to a HHA because a proximal femoral fracture.
