Meta-analysis shows lower prosthetic joint infection odds with cephalosporins versus non-cephalosporin prophylaxis in primary arthroplasty

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Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Published May 21, 2026 Medically reviewed May 21, 2026 Study authors: Igwilo-Alaneme Rita, Berbari Elie, McHugh Jack, Petri Francesco, Ravi Vasupriya, Matsuo Takahiro, Bo… PubMed ↗ DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider cephalosporins as preferred prophylaxis for primary arthroplasty given moderate evidence of lower infection odds.

This systematic review and meta-analysis examined the efficacy of single-agent cephalosporin prophylaxis compared to single-agent non-cephalosporin antibiotics in adults undergoing primary arthroplasty. The analysis included a substantial number of procedures across the cephalosporin and non-cephalosporin arms. The primary outcome focused on prosthetic joint infection, while surgical site infection served as a secondary outcome.

The results indicated that the odds of prosthetic joint infection were lower with cephalosporins. In contrast, no overall difference was observed regarding surgical site infection between the two antibiotic classes. The authors noted that randomized trial estimates were limited and heterogeneous, which prevented the findings from reaching statistical significance in certain contexts.

The authors highlighted that evidence comparing outcomes across antibiotic classes remains variable. They graded the certainty of the evidence as moderate and explicitly advised against inferring causation from the observed associations. Consequently, cephalosporins, particularly cefazolin or cefuroxime, remain the preferred prophylactic agents for primary arthroplasty based on current practice relevance.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedMay 2026

PMID41831307

View Original 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.