Abstract
Aim
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).
Method
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 from a central venous catheter 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)).
Results
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.
Conclusions
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.
Acknowledgments
We would like to thank Department of Clinical Medicine, the surgical research laboratories, Aarhus University Hospital and Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark, for supporting this study.
This research was funded by Novo Nordisk Foundation, grant number [NNF20OC0062032, 2020].
