Intrawound vancomycin powder in orthopaedic surgery after the VPIP trial: a critical reappraisal of efficacy, dosing, application plane, and antimicrobial stewardship

Abstract. Topical intrawound vancomycin powder has been widely adopted in orthopaedic surgery as an adjunct for the prevention of surgical site infection (SSI) and periprosthetic joint infection (PJI). Retrospective cohorts and derived meta-analyses have long suggested a consistent benefit, and the technique became established practice at many institutions. Over the past 5 years, prospective randomised evidence has added an important corrective to this picture. The VPIP trial (Saba et al., 2025) randomised 1901 high-risk patients undergoing primary hip or knee arthroplasty across 17 US centres and found no benefit of vancomycin, dilute povidone-iodine, or their combination over saline for any 3-month infection endpoint; a biostatistical projection to 80 000 patients left the number needed to treat near 500, and enrolment was closed for statistical futility. The VANCO trial in high-risk tibial fractures (O'Toole et al., 2021) narrowly missed its primary endpoint (P=0.06) but demonstrated a significant post hoc reduction in gram-positive deep infections without gram-negative shift. Mechanistic data indicate that sub-inhibitory vancomycin concentrations increase Staphylococcus aureus biofilm formation and raise infection rates in vivo – an effect not reproduced by cefazolin. Current international guidance does not issue a general recommendation for topical vancomycin, a position consistent with this more differentiated evidence base. The present review integrates these strands into an indication-specific framework that separates prophylactic application in clean surgical fields, where benefit is now in serious doubt, from adjunctive-therapeutic application in established infection, and identifies the settings in which topical vancomycin may still be considered individually and those in which it should be avoided.