Cefazolin Versus Non-Cefazolin Prophylaxis in Beta-Lactam Allergy-Labeled Patients Undergoing Hip and Knee Arthroplasty: A Systematic Review
DOI:
https://doi.org/10.37287/ijghr.v8i6.2762Keywords:
beta-lactam allergy, cefazolin, hip arthroplasty, knee arthroplasty, penicillin allergyAbstract
Cefazolin is the preferred perioperative prophylactic antibiotic for hip and knee arthroplasty, but patients with beta-lactam allergy labels often receive second-line agents such as clindamycin or vancomycin. This practice may reduce prophylactic effectiveness despite the low likelihood of true cefazolin cross-reactivity. This systematic review evaluated the effectiveness and safety of cefazolin compared with non-cefazolin antibiotic prophylaxis in beta-lactam allergy-labeled patients undergoing hip and knee arthroplasty. PubMed, Cochrane Library, and ScienceDirect were searched for studies assessing perioperative prophylaxis in arthroplasty patients with penicillin, cephalosporin, or beta-lactam allergy labels. Outcomes included surgical site infection, periprosthetic joint infection, hypersensitivity reaction, anaphylaxis, adverse events, cefazolin utilization, and stewardship-related outcomes. Thirteen observational studies published between 2016 and 2026 were included, and findings were synthesized narratively. Cefazolin was generally associated with lower or comparable infection rates compared with non-cefazolin prophylaxis. Direct comparative studies reported lower surgical site infection and periprosthetic joint infection with cefazolin in several cohorts, while others showed no significant difference. Hypersensitivity reactions to cefazolin were rare and mostly mild. Safety was also observed among patients with reported penicillin anaphylaxis or cephalosporin allergy. Allergy testing, test-dose protocols, and multidisciplinary stewardship interventions increased cefazolin use without increasing perioperative allergic reactions. The evidence suggests that many beta-lactam allergy labels are not clinically relevant contraindications to cefazolin. Routine substitution with clindamycin or vancomycin may expose patients to inferior prophylactic coverage and avoidable adverse effects. Cefazolin should be considered for most beta-lactam allergy-labeled arthroplasty patients after structured allergy assessment, while non-cefazolin agents should be reserved for confirmed high-risk reactions.
References
Allan, L. P., Silvera-Tawil, D., Cameron, J., Li, J., Varnfield, M., Smallbon, V., Bomke, J., Olaiya, M. T., Lannin, N. A., & Cadilhac, D. A. (2024). Novel Multicomponent Digital Care Assistant and Support Program for People After Stroke or Transient Ischaemic Attack: A Pilot Feasibility Study. Sensors, 24(22). https://doi.org/10.3390/s24227253
Anderson, J. A., Kimmel, B., Sansgiry, S., Venkatasubba Rao, C. P., Ovalle, A. P., Cerra-Stewart, C. A., & Kent, T. A. (2022). Using Mobile Video-Teleconferencing to Deliver Secondary Stroke Prevention Interventions: A Pilot Study. Telemedicine Reports, 3(1), 175–183. Blumenthal, K. G., Ryan, E. E., Li, Y., Lee, H., Kuhlen, J. L., & Shenoy, E. S. (2018). The impact of a reported penicillin allergy on surgical site infection risk. Clinical Infectious Diseases, 66(3), 329–336. https://doi.org/10.1093/cid/cix794
Guido, J. M., Hudock, N. L., Frye, B. M., Parrish, K. L., Lastinger, A. M., Howard, C. A., Matyus, V. L., Leadman, K. M., Pincavitch, J. D., & Peppers, B. P. (2026). Standardizing safe cefazolin use in total joint arthroplasty: A multidisciplinary triage protocol. The Journal of Arthroplasty, 41(10S1), S133–S138. https://doi.org/10.1016/j.arth.2026.03.100
Jones, R., Quartuccio, K. S., Stern, J. L., Heintz, E. V., Pillinger, K. E., & Myers, T. G. (2021). Antibiotic stewardship interventions improve choice of antibiotic prophylaxis in total joint arthroplasty in patients with reported penicillin allergies. Clinical Orthopaedics and Related Research, 479(7), 1484–1494. https://doi.org/10.1097/CORR.0000000000001739
Khan, D. A., Banerji, A., Blumenthal, K. G., Phillips, E. J., Solensky, R., White, A. A., Bernstein, J. A., Chu, D. K., Ellis, A. K., Golden, D. B. K., Greenhawt, M. J., Horner, C. C., Ledford, D., Lieberman, J. A., Oppenheimer, J., Rank, M. A., Shaker, M. S., Stukus, D. R., Wallace, D., & Wang, J. (2022). Drug allergy: A 2022 practice parameter update. Journal of Allergy and Clinical Immunology, 150(6), 1333–1393. https://doi.org/10.1016/j.jaci.2022.08.028
Mannarino, M., Montreuil, J., Tanzer, M., & Hart, A. (2023). Local tissue concentrations of cefazolin during total joint arthroplasty: A systematic review. Canadian Journal of Surgery, 66(4), E415–E421. https://doi.org/10.1503/cjs.019621
McDanel, D. L., Azar, A. E., Dowden, A. M., Murray-Bainer, S., Noiseux, N. O., Willenborg, M., Clark, C. R., Callaghan, J. J., & Haleem, A. (2017). Screening for beta-lactam allergy in joint arthroplasty patients to improve surgical prophylaxis practice. The Journal of Arthroplasty, 32(9), S101–S108. https://doi.org/10.1016/j.arth.2017.01.012
Norvell, M. R., Porter, M., Ricco, M. H., Koonce, R. C., Hogan, C. A., Basler, E., Wong, M., & Jeffres, M. N. (2023). Cefazolin vs second-line antibiotics for surgical site infection prevention after total joint arthroplasty among patients with a beta-lactam allergy. Open Forum Infectious Diseases, 10(6), ofad224. https://doi.org/10.1093/ofid/ofad224
Sousa-Pinto, B., Blumenthal, K. G., Courtney, L., Mancini, C. M., & Jeffres, M. N. (2021). Assessment of the frequency of dual allergy to penicillins and cefazolin: A systematic review and meta-analysis. JAMA Surgery, 156(4), e210021. https://doi.org/10.1001/jamasurg.2021.0021
Stevoska, S., Behm-Ferstl, V., Zott, S., Stadler, C., Schieder, S., Luger, M., Gotterbarm, T., & Klasan, A. (2022). The impact of patient-reported penicillin or cephalosporin allergy on the occurrence of the periprosthetic joint infection in primary knee and hip arthroplasty. Antibiotics, 11(10), 1345. https://doi.org/10.3390/antibiotics11101345
Tan, T. L., Springer, B. D., Ruder, J. A., Ruffolo, M. R., & Chen, A. F. (2016). Is vancomycin-only prophylaxis for patients with penicillin allergy associated with increased risk of infection after arthroplasty? Clinical Orthopaedics and Related Research, 474(7), 1601–1606. https://doi.org/10.1007/s11999-015-4672-4
Wu, V. J., Iloanya, M. C., Sanchez, F. L., Billings, C. R., O’Brien, M. J., Savoie, F. H., III, & Sherman, W. F. (2020). Is patient-reported penicillin allergy independently associated with increased risk of prosthetic joint infection after total joint arthroplasty of the hip, knee, and shoulder? Clinical Orthopaedics and Related Research, 478(12), 2699–2709. https://doi.org/10.1097/CORR.0000000000001497
Wyles, C. C., Hevesi, M., Osmon, D. R., Park, M. A., Habermann, E. B., Lewallen, D. G., Berry, D. J., & Sierra, R. J. (2019). 2019 John Charnley Award: Increased risk of prosthetic joint infection following primary total knee and hip arthroplasty with the use of alternative antibiotics to cefazolin: The value of allergy testing for antibiotic prophylaxis. The Bone & Joint Journal, 101-B(6_Supple_B), 9–15. https://doi.org/10.1302/0301-620X.101B6.BJJ-2018-1407.R1 https://doi.org/10.1089/tmr.2022.0026
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Indonesian Journal of Global Health Research
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
