Cefazolin Alone Versus Vancomycin Plus Cefazolin for Intravenous Prophylaxis in Hip and Knee Arthroplasty: A Systematic Review and Meta-Analysis.

BACKGROUND: Periprosthetic joint infection (PJI) remains a devastating complication following total joint arthroplasty, leading to substantial morbidity and increased healthcare costs. Cefazolin is the standard agent for perioperative antibiotic prophylaxis. However, the rising prevalence of methicillin-resistant Staphylococcus aureus (MRSA) has prompted the use of dual prophylaxis with vancomycin and cefazolin. The efficacy and safety of this combined strategy remain controversial. METHODS: A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered on the international prospective register of systematic reviews (ID CRD420251077695). A comprehensive search of PubMed, Web of Science, Embase, and the Cochrane Library was performed. Randomized controlled trials and observational studies directly comparing cefazolin alone with combined vancomycin and cefazolin as intravenous prophylaxis in patients undergoing total joint arthroplasty were included. The primary outcome measures were PJI and SSI (surgical site infection), and secondary outcome measures were AKI (acute kidney injury). RESULTS: Eight studies including 1,041,058 patients met the inclusion criteria. Dual prophylaxis was associated with a higher risk of SSI (odds ratio [OR] =1.39; 95% confidence interval [CI] = 1.23 to 1.58), but a lower risk of PJI (OR = 0.64; 95% CI = 0.46 to 0.91). There was no significant difference in risk of AKI between regimens (OR = 1.30; 95% CI = 0.76 to 2.20), although substantial heterogeneity was observed among studies reporting renal outcomes. CONCLUSIONS: Routine addition of vancomycin to cefazolin does not reduce overall SSI rates and may increase superficial infections. However, it may decrease PJI risk without significantly increasing AKI. These findings support a selective, risk-stratified prophylactic strategy rather than universal dual antibiotic therapy in total joint arthroplasty.