Aim

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.

Introduction

The Vancouver Classification System presents a systematic approach to classification of periprosthetic fractures of the proximal femur (PFPFs) that has been validated in previous studies. However, with the introduction of tapered fluted stems and cable plates since the introduction of the Vancouver System, the connection between fracture class and the preferred method of treatment is often unclear. The present study was undertaken to identify fracture patterns surrounding contemporary femoral stems and the relationship between the current method of treatment and the Vancouver Class of the periprosthetic fracture.

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.

Although linezolid has been used in the therapy of osteoarticular infections (OI), there is little information about its effectiveness and safety in prolonged therapy for OI.

Therefore the aim of our study was to assess the effectiveness and tolerability in OI and retrospectively evaluate multi-resistant gram-positive OI treated with linezolid 600 mg bid orally.

Between January 2003 and January 2007, 20 patients (10 men, mean age: 65 years) with 23 episodes of OI (19 of them associated with implants including 16 prosthetic joints) were treated with linezolid. In all but one episode, vitamin B6 was administered. Five were diabetic and 1 had renal insufficiency. All but two cases had infections due to multi-resistant coagulase-negative staphylococci. The median duration of therapy was 12.3 weeks (range 4–36 weeks). In 9 episodes the implant was removed. At the end of the therapy, response was observed in 22/23 (95.6%) of the episodes, and at the follow-up 10 relapses occurred (median duration: 1 month) resulting in an overall successful rate of cure of 12/23 (52.2%). The cure rate in episodes with and without implant removal was 6/9 (66.7%) and 3/10 (30%), respectively, while in the cases without implant 3/4 (75%). Adverse events that required drug discontinuation were observed in 10 (43.5%) episodes: anemia in 6/10 (60%), gastrointestinal in 6/10 (60%), lactic acidosis in two, teeth pigmentation in two and optic neuritis in one. Risk factors associated with secondary effects were: older age, diabetes mellitus and renal insufficiency. One patient developed anemia after one month; linezolid was stopped and restarted with vitamin B6 and no anemia was observed after 9 months of therapy.

Linezolid may be useful in multi-resistant gram-positive OI, especially when the implant is removed. However, with prolonged therapy, side effects are common, thus close monitoring for severe complications is needed.