Multicentre randomized double-blind placebo-controlled trial of combination vancomycin and cefazolin surgical antibiotic prophylaxis in arthroplasty surgery

There is an increasing incidence of revision for periprosthetic joint infection. The addition of vancomycin to beta-lactam antimicrobial prophylaxis in joint arthroplasty may reduce surgical site infections, however, the efficacy and safety have not been established. This was a multicenter, double-blind, superiority, placebo-controlled trial. We randomized 4239 adult patients undergoing joint arthroplasty surgery to receive 1.5g vancomycin or normal saline placebo, in addition to standard cefazolin antimicrobial prophylaxis. The primary outcome was surgical site infection at 90-days from index surgery. Perioperative carriage of Staphylococcus species was also assessed. In the 4113 patients included in the modified intention-to-treat population, surgical site infections occurred in 72/2069 (3.5%) in the placebo group and 91/2044 (4. 5%) in the vancomycin group (risk ratio 1.28; 95% confidence interval 0.94 to 1.73; p value 0.11). No difference was observed between the two groups for primary hip arthroplasty procedures. A higher proportion of infections occurred in knee arthroplasty patients in the vancomycin group (63/1109 [4.7%]) compared with the placebo group (42/1124 [3.7%]; risk ratio 1.52; 95% confidence interval 1.04 to 2.23; p value 0.031). Hypersensitivity reactions occurred in 11 (0.5%) patients in the placebo group and 24 (1.2%) in the vancomycin group (risk ratio 2.20; 95% confidence interval 1.08, 4.49) and acute kidney injury in 74 (3.7%) patients in the placebo group and 42 (2.1%) in the vancomycin group (risk ratio 0.57; 95% confidence interval 0.39, 0.83). Perioperative Staphylococcus aureus carriage was detected in 1089/3748 (29.1%) of patients. This is the first randomized controlled trial examining the addition of a glycopeptide antimicrobial to standard beta-lactam surgical antimicrobial prophylaxis in joint arthroplasty. The addition of vancomycin to standard cefazolin prophylaxis was not superior to placebo for the prevention of surgical site infections in hip and knee arthroplasty surgery.