High Cefuroxime Concentrations and Long Elimination in an Orthopaedic Surgical Deadspace—A Microdialysis Porcine Study

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.

Steady-State Piperacillin Concentrations in the Proximity of an Orthopedic Implant: A Microdialysis Porcine Study

“…A deadspace is presumably a poorly vascularized void with low oxygen tension and pH, which may favour bacterial proliferation and biofilm formation [ 25 ]. A recent microdialysis study has demonstrated the same tendencies of longer elimination of cefuroxime from a physiological hematoma deadspace, indicating longer diffusion distance and lower antibiotic turn-over in a deadspace [ 26 ]. Although being a mechanical deadspace, the present experimental design using a cannulated screw reflects that of several clinically relevant orthopedic settings.…”

Intravenous Cefazolin Achieves Sustained High Interstitial Concentrations in Open Lower Extremity Fractures

“…Although prophylactic antibiotic delivery to traumatized tissues is a tenet of open fracture management [2,6,7,10,11,15,[17][18][19], the risk of deep infection for open lower extremity fractures remains unacceptably high [8]. Soft tissue trauma alters tissue homeostasis; however, its impact on local antibiotic delivery has been poorly characterized.…”

“…The pharmacokinetics of intravenously administered antibiotics can be measured using direct sampling techniques such as microdialysis. Microdialysis is a validated method that has been successfully used in animal and human clinical research [1,3,6,7,11,13,[16][17][18][19]. It has been used to quantify local antibiotic delivery to compromised soft tissues.…”