Single- vs Multiple-Dose Antibiotic Prophylaxis for Total Hip Arthroplasty

Importance: In primary total hip arthroplasty (THA), studies suggest that a single preoperative antibiotic dose is noninferior to multiple doses for preventing periprosthetic joint infection (PJI). However, this evidence largely derives from older, heterogeneous trials. Objective: To compare single- vs multiple-dose perioperative antibiotic prophylaxis for preventing PJI after primary THA for osteoarthritis. Design, Setting, and Participants: This comparative effectiveness research study used a target trial emulation approach to analyze Danish registry and microbiology data on primary THA procedures performed between January 1, 2010, and December 31, 2020, with follow-up up to 1 year. The population-based, multicenter cohort included all hospitals performing THA in Denmark, and a total of 76 126 patients underwent primary THA for osteoarthritis. Data were analyzed from July 1, 2025, to October 15, 2025. Exposure: Single preoperative antibiotic dose vs multiple prophylactic doses administered within 24 hours postoperatively. Main Outcomes and Measures: The primary outcome was PJI within 90 days, defined as microbiologically confirmed infection or a clinical diagnosis recorded at revision surgery. Secondary outcomes included PJI likely, any revision, hospital-treated infection, community-based antibiotic use, mortality, and PJI within 365 days. Treatment effects were estimated using stabilized inverse probability of treatment weighting and weighted logistic regression. Noninferiority was defined as an upper 95% CI for the odds ratio (OR) less than 1.40. Results: The cohort comprised 76 126 patients (mean [SD] age, 68.8 [11.0] years; 42 559 women (55.9%), including 6409 who received single-dose and 69 717 who received multiple-dose antibiotic prophylaxis. PJI within 90 days occurred in 63 patients (0.98%) in the single-dose group and 656 patients (0.94%) in the multiple-dose group. Weighted analyses yielded an OR of 0.97 (95% CI, 0.73-1.29), meeting the prespecified noninferiority criterion. Sensitivity analysis results were consistent for PJI at 90 and 365 days and across secondary outcomes and unadjusted, weighted, and propensity score-matched analyses. Conclusions and Relevance: In this study, a single preoperative antibiotic dose was noninferior to multiple doses for preventing PJI. These findings support efforts to minimize perioperative antibiotic exposure, although confirmation in randomized clinical trials is warranted.