Cephalosporins Versus Non-cephalosporin Antibiotics for Perioperative Prophylaxis in Primary Arthroplasty: A Systematic Review and Meta-Analysis

Clinical Snapshot

Key Findings

• P Value: Statistically significant (p<0.05 implied)

• Effect Size: OR 0.59 favouring cephalosporins

• Primary Outcome: Prosthetic joint infection (PJI)

• Nnt Or Sensitivity: 41% reduction in odds of PJI with cephalosporin prophylaxis

• Confidence Interval: 95% CI: 0.46-0.75

Clinical Application

Highly feasible - cefazolin and cefuroxime readily available and cost-effective in Australian healthcare system Aligns with current ANZICS and ASID guidelines. Cefazolin listed on PBS for surgical prophylaxis. Supports TGA-approved indications for perioperative prophylaxis Adults undergoing primary hip or knee arthroplasty in Australian public and private hospitals

Abstract

BACKGROUND: The number of arthroplasty procedures and infection-related complications, including prosthetic joint infections (PJIs) and surgical site infections (SSIs), continues to rise. Although current guidelines recommend cefazolin or cefuroxime as the first-line perioperative prophylactic antibiotic, substitutions with non-cephalosporins remain common, especially among patients with reported β-lactam allergies. These substitutions may increase infection risk and healthcare costs. Evidence comparing outcomes across antibiotic classes remains variable. METHODS: We conducted a systematic review and meta-analysis of studies comparing single-agent cephalosporin versus single-agent non-cephalosporin prophylaxis in adults undergoing primary arthroplasty. Cochrane, Embase, Medline, Scopus, and Web of Science were searched from database inception through January 2025. Random-effect or fixed-effect models were used to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). Subgroup analyses stratified results by cephalosporin type, study era, and risk of bias. RESULTS: Twenty-three studies (7 randomized controlled trials and 16 observational studies) were included, encompassing 191 527 arthroplasties in the cephalosporin arm and 20 058 in the non-cephalosporin arm. The odds of PJI were lower with cephalosporins (OR 0.59; 95% CI, .46-.75). No overall difference was observed for SSI (OR 0.70; 95% CI, .36-1.36), though post-2013 studies and the cefazolin subgroup demonstrated a significant protective effect. Randomized trial estimates were limited and heterogeneous and did not reach statistical significance. Certainty of evidence was graded as moderate. CONCLUSIONS: Cephalosporins, particularly cefazolin or cefuroxime, remain the preferred prophylactic agents for primary arthroplasty. This quantitative synthesis reinforces their protective association against prosthetic joint infection and supports adherence to guideline-endorsed prophylaxis.

References

1. 1.Igwilo-Alaneme, R., Berbari, E., McHugh, J., Petri, F., Ravi, V., Matsuo, T., Borgonovo, F., El Zein, S., Murad, M. H., & Tande, A. (2026). Cephalosporins versus non-cephalosporin antibiotics for perioperative prophylaxis in primary arthroplasty: A systematic review and meta-analysis. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciag172