JOA - 2026-05-22 - Journal Article
The Efficacy of Cefazolin Alternatives for Periprosthetic Joint Infection Prevention after Primary Total Hip and Knee Arthroplasty: A Systematic Review and Meta-Analysis.
Kanumuri SD, Dasari SP, Roth OS, Yang J, Fernando N, Hernandez N
Topics
Key Takeaway
Cefazolin reduces PJI risk by 45% versus vancomycin ± clindamycin and 34% versus non-cephalosporin antibiotics, with no significant difference against higher-generation cephalosporins across 2,303,501 TJA patients.
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Summary
This systematic review and meta-analysis compared PJI rates between cefazolin and non-cefazolin prophylaxis regimens across 18 studies in primary THA and TKA patients. Using a random effects model, cefazolin was associated with 45% lower PJI risk versus vancomycin ± clindamycin (P=0.004) and 34% lower risk versus all non-cephalosporin antibiotics (P=0.004). No significant difference in PJI rates was identified between cefazolin and higher-generation cephalosporins, suggesting cephalosporin class efficacy is comparable but first-generation remains superior to non-cephalosporin alternatives.
Key Limitation
The I²=88% heterogeneity indicates that differences in patient selection, allergy status, MRSA colonization rates, and antibiotic timing across included studies likely confound the pooled risk estimates, making causal inference unreliable.
Original Abstract
BACKGROUND
Periprosthetic joint infection (PJI) remains a challenging complication following total joint arthroplasty (TJA). Current guidelines recommend the use of first-generation cephalosporins for prophylactic antibiotic coverage. The primary aim of this investigation was to determine if there was a difference in the incidence of postoperative PJI between TJA patients who were treated with cefazolin and non-cefazolin prophylaxis. The secondary aim of this study was to evaluate differences among those treated with cefazolin prophylaxis and higher generation cephalosporins.
METHODS
Multiple databases were queried for literature comparing the clinical outcomes between patients who were treated with cefazolin prophylaxis and those treated with non-cefazolin prophylaxis, including higher-generation cephalosporins. The primary outcome was PJI rates. A random effects model was used to compare the relative risk of PJI in the two pooled cohorts. There was a total of 2,303,501 patients included in this study across 18 studies.
RESULTS
Patients who were treated with cefazolin were 45% less likely to develop a PJI relative to patients who were treated with vancomycin with/without clindamycin (P = 0.004). Patients who were treated with cefazolin were 34% less likely to develop a PJI relative to patients who were treated with non-cephalosporin antibiotics (P = 0.004). When comparing patients who were treated with cefazolin with those who were treated with higher-generation cephalosporins, there were no significant differences. Further studies are needed to assess variability due to heterogeneity in effect sizes across the meta-analysis (I 2 = 88%, Tau 0.20), likely from differences within antibiotic regimens.
CONCLUSION
Compared to all non-cephalosporin antibiotics and specifically vancomycin with/without clindamycin, cefazolin was associated with a significantly lower rate of PJI following TJA. There were no significant differences observed when comparing cefazolin to higher generation cephalosporins. Further research is warranted to elucidate the ideal antibiotic prophylaxis for total joint arthroplasty, especially given differences in timing and reasons for selection of antibiotics.