EXTENDED SURGICAL ANTIBIOTIC PROPHYLAXIS NOT SUPERIOR TO A SINGLE DOSE IN TOTAL HIP AND KNEE REVISION ARTHROPLASTY: A MULTICENTRE OPEN-LABEL RANDOMIZED CONTROLLED TRIAL

Aim Periprosthetic joint infection (PJI) is a severe complication after total joint arthroplasty. To prevent PJI, strict infection prevention measures are followed in combination with surgical antibiotic prophylaxis (SAP). To date, scientific reports concerning the optimal duration of SAP in revision arthroplasty are scarce. The aim of this multicenter open-label, randomized controlled trial in the Netherlands, is to investigate the superiority of 5 days (extended) versus a single dose of cefazolin to prevent PJI within the first year after revision arthroplasty of the hip and knee. Method Included patients with an assumed aseptic hip or knee revision procedure received a single dose of 2 or 3 gram cefazolin preoperatively. Patients were randomly assigned in a 1:1 ratio to receive extended prophylaxis of cefazolin during 5 days postoperatively versus no prophylaxis after wound closure. Patients were excluded if evidence of PJI at revision. The primary endpoint was the incidence of PJI within one year after revision arthroplasty. PJI was defined according to the 2018 Philadelphia consensus criteria. With a sample size of 746 patients, an alpha of 5% and a power of 80%, superiority of the extended regimen would be shown if the lower boundary of the 95% confidence interval (CI) of the absolute between-group difference of the percentage of PJI is below −4%. Results In total 751 patients were included for analysis: 379 in the single dose cefazolin group and 372 in the extended group. Within one year, PJI occurred in 2.6% (10/379) in the single dose group and 2.4% (9/372) in the extended group (risk difference, −0.2 percentage points; 95% CI, −2.5 to 2.0%), thus superiority was not shown. Adverse drug events were seen in 20 cases with extended and 7 cases with a single dose prophylaxis. Conclusions Extended prophylaxis is not significantly superior to a single dose of cefazolin to prevent PJI within the first year after revision arthroplasty of the hip or knee. This is the first randomized controlled trail in which the duration of SAP in the selected group of patients undergoing revision arthroplasty was studied. Extending SAP after closure of the wound could increase the selection or induction of antimicrobial resistance, has an increased risk for adverse drug events, and is therefore not in line with the primary goal of antimicrobial stewardship, comprising optimizing clinical outcomes and ensuring cost-effective therapy while minimizing unintended consequences of antimicrobial use.