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. 2025 Jun 21:S0883-5403(25)00783-1.
doi: 10.1016/j.arth.2025.06.057. Online ahead of print.

Noncefazolin Antibiotic Prophylaxis Is Associated With Increased Periprosthetic Joint Infection Risk Following Total Knee Arthroplasty

Kranti C Rumalla  1 , Isaac L Sontag-Milobsky  2 , Austin R Chen  1 , T Jacob Selph  1 , Tyler M Compton  2 , Adam I Edelstein  2
Affiliations

Noncefazolin Antibiotic Prophylaxis Is Associated With Increased Periprosthetic Joint Infection Risk Following Total Knee Arthroplasty

Kranti C Rumalla et al. J Arthroplasty. .

Abstract

Background: Conflicting reports exist on the relationship between antibiotic choice and periprosthetic joint infection (PJI) after total knee arthroplasty (TKA). We used a national database to investigate whether cefazolin usage reduced PJI risk compared with alternatives.

Methods: We queried a national database from 2016 to 2022 to identify primary TKAs using Current Procedural Terminology code 27447 and International Classification of Diseases Procedure Coding System codes (0SRD0xx, 0SRC0xx) linked to osteoarthritis (International Classification of Diseases Clinical Modification M17). This study included 528,250 primary TKA patients. A total of 53,776 (10.2%) received noncefazolin alone, 343,279 (65.0%) received cefazolin only, and 131,195 (24.8%) received cefazolin plus another antibiotic. Demographics, clinical characteristics, and outcomes were extracted. The PJIs were defined according to Centers for Medicare and Medicaid Services complication measure codes within 90 days. We compared three prophylaxis groups: cefazolin only, noncefazolin, or cefazolin plus another antibiotic. Multinomial logistic regression assessed the association between antibiotic use and PJI.

Results: Univariate analysis showed 90-day PJI rates of 1.0% in noncefazolin versus 0.7% in both cefazolin-only and combination groups (P < 0.001). After adjusting for age, sex, payer, race, ethnicity, and comorbidities, both cefazolin-only (odds ratio 0.68, 95% confidence interval 0.62 to 0.75, P < 0.001) and cefazolin plus another antibiotic (odds ratio 0.74, 95% confidence interval 0.66 to 0.82, P < 0.001) were associated with reduced odds of PJI.

Conclusions: In conclusion, our nationally representative findings confirm that cefazolin prophylaxis significantly lowers 90-day PJI risk after TKA compared to alternative antibiotics. Surgeons should carefully consider patient allergies before deviating from cefazolin-based prophylaxis. Future research should clarify optimal strategies for patients reporting cefazolin allergies and those at higher infection risk, particularly immunocompromized patients.

Keywords: Ancef; antibiotic prophylaxis; peri-operative care; periprosthetic joint infection; total knee arthroplasty.

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