Abstract
Deadspace is the tissue and bony defect in a surgical wound after closure. This space is presumably poorly perfused favouring bacterial proliferation and biofilm formation. In arthroplasty surgery, an obligate deadspace surrounding the prosthesis is introduced and deadspace management, in combination with obtaining therapeutic prophylactic antibiotic concentrations, is important for limiting the risk of acquiring a periprosthetic joint infection (PJI). This study aimed to investigate cefuroxime distribution to an orthopaedic surgical deadspace in comparison with plasma and bone concentrations during two dosing intervals (8 h × 2). In a setup imitating shoulder arthroplasty surgery, but without insertion of a prosthesis, microdialysis catheters were placed for cefuroxime sampling in a deadspace in the glenohumeral joint and in cancellous bone of the scapular neck in eighteen pigs. Blood samples were collected as a reference. Cefuroxime was administered according to weight (20 mg/kg). The primary endpoint was time above the cefuroxime minimal inhibitory concentration of the free fraction of cefuroxime for Staphylococcus aureus (fT > MIC (4 μg/mL)). During the two dosing intervals, mean fT > MIC (4 μg/mL) was significantly longer in deadspace (605 min) compared with plasma (284 min) and bone (334 min). For deadspace, the mean time to reach 4 μg/mL was prolonged from the first dosing interval (8 min) to the second dosing interval (21 min), while the peak drug concentration was lower and half-life was longer in the second dosing interval. In conclusion, weight-adjusted cefuroxime fT > MIC (4 μg/mL) and elimination from the deadspace was longer in comparison to plasma and bone. Our results suggest a deadspace consolidation and a longer diffusions distance, resulting in a low cefuroxime turn-over. Based on theoretical targets, cefuroxime appears to be an appropriate prophylactic drug for the prevention of PJI.
Highlights
Arthroplasty surgery introduces an obligate deadspace surrounding the prosthesis
Surgical and pharmaceutical deadspace management is important to protect the prosthesis from colonisation [4,6]
Abreast of increasing bacterial virulence when introducing foreign materials [26,27], and the ability of bacteria to develop a self-protective biofilm on the implant surface [28] as early as within the first 24 h after surgery [29], the interstitial environment surrounding the prosthesis is often referred to as a vulnerable region with local immune depression [30]. Taking all of these factors into account, the role of adequate prophylactic antibiotic administration may be important to protect the prosthesis from colonisation, and may require antibiotic concentrations several times higher than the employed planktonic targets in arthroplasty surgery [31]
Summary
Arthroplasty surgery introduces an obligate deadspace surrounding the prosthesis. The deadspace volume is dependent on the type of prosthesis and surgical technique [1,2]. Proper deadspace management is considered important to reduce the risk of developing a periprosthetic joint infection (PJI) [4]. PJI is a serious complication following arthroplasty surgery associated with significant morbidity for the patient [5]. In spite of great advancements in the field of orthopaedic devices and surgical techniques, the introduction of foreign materials is still associated with a substantial risk of infection due to increasing bacterial virulence [6,7]. To protect the prosthesis surface from bacterial colonisation and ensure host integration, it is paramount to achieve adequate perioperative prophylactic antibiotic concentrations in the deadspace surrounding the prosthesis [11,12]
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