Trial of Vancomycin and Cefazolin as Surgical Prophylaxis in Arthroplasty

Peel, Trisha N. M.B., B.S., Ph.D.
Astbury, Sarah B.Nurs.
Cheng, Allen C. M.B., B.S., M.Biostat., Ph.D.
Paterson, David L. M.B., B.S., Ph.D.
Buising, Kirsty L. M.B., B.S., M.D.
Spelman, Tim M.B., B.S., Ph.D.
Tran-Duy, An Ph.D.
Adie, Sam M.B., B.S., M.P.H., Ph.D.
Boyce, Glenn M.B., B.S.
McDougall, Catherine M.B., B.S.
Molnar, Robert M.B., B.S.
Mulford, Jonathan M.B., B.S.
Rehfisch, Peter M.B., B.S.
Solomon, Michael M.B., Ch.B.
Crawford, Ross M.B., B.S., D.Phil.
Harris-Brown, Tiffany R.N., M.P.H.
Roney, Janine M.P.H., B.H.Sc., R.N.
Wisniewski, Jessica Ph.D.
de Steiger, Richard M.B., B.S., Ph.D.

From the Department of Infectious Diseases, Central Clinical School, Faculty of Medicine, Nursing, and Health Sciences (T.N.P., S. Astbury, J.W.), and the Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine (A.C.C.), Monash University, the Department of Infectious Diseases, Alfred Health (T.N.P., S. Astbury, A.C.C., J.R., J.W.), the Department of Infectious Diseases, Doherty Institute (K.L.B.), the Department of Surgery, St. Vincent's Hospital (T.S.), the Centre for Health Policy, Melbourne School of Population and Global Health (A.T.-D.), and the Department of Surgery, Epworth HealthCare (R.S.), University of Melbourne, the Victorian Infectious Diseases Service, Royal Melbourne Hospital (K.L.B.), and the Department of Health Services Research, Peter MacCallum Cancer Centre, and Burnet Institute (T.S.), Melbourne, VIC, the St. George and Sutherland Clinical Campuses, School of Clinical Medicine, University of New South Wales Medicine and Health, Sydney (S. Adie, R.M.), Bendigo Health, Bendigo, VIC (G.B.), the Department of Orthopaedics, Prince Charles Hospital, Metro North Hospital and Health Service (C.M., R.C.), the Department of Medicine (C.M.) and the Centre for Clinical Research (T.H.-B.), University of Queensland, and Queensland University of Technology (R.C.), Brisbane, the Department of Orthopaedics, Launceston General Hospital, Tasmanian Health Service, Launceston, TAS (J.M.), Gippsland Orthopaedic Group, Traralgon, VIC (P.R.), and Prince of Wales Hospital and Prince of Wales Private Hospital, Randwick, NSW (M.S.) — all in Australia; Advancing Clinical Evidence in Infectious Diseases, Saw Swee Hock School of Public Health, and the Infectious Diseases Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore (D.L.P.); and the Department of Clinical Neuroscience, Karolinska Institute, Stockholm (T.S.).

Dr. Peel can be contacted at [email protected] or at the Department of Infectious Diseases, Monash University, 85 Commercial Rd., Melbourne, VIC 3004, Australia.

^*The members of the ASAP Trial Group are listed in the Supplementary Appendix, available at NEJM.org.

This is the New England Journal of Medicine version of record, which includes all Journal editing and enhancements. The Author Accepted Manuscript, which is the author's version after external peer review and before publication in the Journal, is available at PubMed Central.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

Supported by a grant (APP1120331) from the Australian National Health and Medical Research Council.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

New England Journal of Medicine 389(16):p 1488-1498, October 19, 2023. | 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.)

Vancomycin and Cefazolin Prophylaxis in Arthroplasty

In this double-blind, randomized trial, vancomycin was added to cefazolin as surgical prophylaxis for arthroplasty. Surgical-site infections occurred in 4.5% of vancomycin recipients and 3.5% of placebo recipients.