Trial of Vancomycin and Cefazolin as Surgical Prophylaxis in Arthroplasty

N Engl J Med. 2023 Oct 19;389(16):1488-1498. doi: 10.1056/NEJMoa2301401.

Abstract

Background: The addition of vancomycin to beta-lactam prophylaxis in arthroplasty may reduce surgical-site infections; however, the efficacy and safety are unclear.

Methods: In this multicenter, double-blind, superiority, placebo-controlled trial, we randomly assigned adult patients without known methicillin-resistant Staphylococcus aureus (MRSA) colonization who were undergoing arthroplasty to receive 1.5 g of vancomycin or normal saline placebo, in addition to cefazolin prophylaxis. The primary outcome was surgical-site infection within 90 days after surgery.

Results: A total of 4239 patients underwent randomization. Among 4113 patients in the modified intention-to-treat population (2233 undergoing knee arthroplasty, 1850 undergoing hip arthroplasty, and 30 undergoing shoulder arthroplasty), surgical-site infections occurred in 91 of 2044 patients (4.5%) in the vancomycin group and in 72 of 2069 patients (3.5%) in the placebo group (relative risk, 1.28; 95% confidence interval [CI], 0.94 to 1.73; P = 0.11). Among patients undergoing knee arthroplasty, surgical-site infections occurred in 63 of 1109 patients (5.7%) in the vancomyin group and in 42 of 1124 patients (3.7%) in the placebo group (relative risk, 1.52; 95% CI, 1.04 to 2.23). Among patients undergoing hip arthroplasty, surgical-site infections occurred in 28 of 920 patients (3.0%) in the vancomyin group and in 29 of 930 patients (3.1%) in the placebo group (relative risk, 0.98; 95% CI, 0.59 to 1.63). Adverse events occurred in 35 of 2010 patients (1.7%) in the vancomycin group and in 35 of 2030 patients (1.7%) in the placebo group, including hypersensitivity reactions in 24 of 2010 patients (1.2%) and 11 of 2030 patients (0.5%), respectively (relative risk, 2.20; 95% CI, 1.08 to 4.49), and acute kidney injury in 42 of 2010 patients (2.1%) and 74 of 2030 patients (3.6%), respectively (relative risk, 0.57; 95% CI, 0.39 to 0.83).

Conclusions: The addition of vancomycin to cefazolin prophylaxis was not superior to placebo for the prevention of surgical-site infections in arthroplasty among patients without known MRSA colonization. (Funded by the Australian National Health and Medical Research Council; Australian New Zealand Clinical Trials Registry number, ACTRN12618000642280.).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anti-Bacterial Agents* / adverse effects
  • Anti-Bacterial Agents* / therapeutic use
  • Antibiotic Prophylaxis* / adverse effects
  • Antibiotic Prophylaxis* / methods
  • Arthroplasty, Replacement* / adverse effects
  • Arthroplasty, Replacement* / methods
  • Arthroplasty, Replacement* / statistics & numerical data
  • Arthroplasty, Replacement, Knee / adverse effects
  • Arthroplasty, Replacement, Knee / methods
  • Australia
  • Cefazolin* / adverse effects
  • Cefazolin* / therapeutic use
  • Double-Blind Method
  • Humans
  • Methicillin-Resistant Staphylococcus aureus
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / epidemiology
  • Staphylococcal Infections / prevention & control
  • Surgical Wound Infection* / epidemiology
  • Surgical Wound Infection* / etiology
  • Surgical Wound Infection* / prevention & control
  • Vancomycin* / adverse effects
  • Vancomycin* / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Cefazolin
  • Vancomycin

Associated data

  • ANZCTR/ACTRN12618000642280