Abstract:
Aims The aim of the research underpinning this thesis was to investigate the use of prophylactic antibiotics by intraosseous regional administration (IORA) in total knee arthroplasty (TKA) patients . The research aimed to identify which organisms cause periprosthetic joint infection (PJI), the relative importance of PJI as a failure mechanism in TKA, compared the tissue concentrations of cefazolin and vancomycin achieved via the IORA route versus systemic administration in primary and revision TKA, and whether IORA provides more effective prophylaxis in a murine model of TKA. Methods Six studies are presented. Two studies retrospectively reviewed patients who underwent TKA across three public hospitals in Auckland to identify the mechanisms of TKA failure and the causative organisms in PJI. Three prospective randomised clinical trials compared tissue concentrations of cefazolin and vancomycin achieved with IORA versus systemic administration in both primary and revision TKA. Antibiotic prophylaxis by IORA is given as a bolus injection into a tibial intraosseous cannula below an inflated thigh tourniquet, immediately before skin incision. Subcutaneous fat and bone samples were taken during the procedure and antibiotic concentrations were measured using high-performance liquid chromatography. Finally, the effectiveness of antibiotic prophylaxis delivered by IORA was investigated in a mouse model of TKA. Findings The most common reason for revision following TKA over 15 years was PJI, and the most common infecting organisms were coagulase-negative staphylococci (CoNS). Ninety-two percent of CoNS strains were resistant to cefazolin, the antibiotic typically used for prophylaxis in TKA. The mean tissue concentrations of antibiotics in subcutaneous fat and bone were 4–10 times higher with IORA than with systemic administration in both primary and revision TKA. These differences were consistent across all sample time points. In the murine model of TKA, vancomycin delivered via IORA afforded the most effective prophylaxis against PJI. Conclusions PJI is the dominant cause of failure in modern TKA, and most infections are caused by bacteria resistant to commonly used prophylactic agents. When antibiotic prophylaxis is delivered via IORA, markedly higher tissue antibiotic concentrations are achieved. IORA has the potential to enhance the effectiveness of prophylaxis to prevent PJI in TKA.