Introduction
Cefazolin is a preferred antibiotic for perioperative prophylaxis due to its spectrum of activity, efficacy, tolerability, affordability, and ease of administration.Reference Bratzler, Dellinger and Olsen1 The use of alternative agents such as vancomycin or clindamycin is associated with higher risk of surgical site infections (SSIs), adverse effects, and higher cost.Reference Bhathal, Joseph, Nailor and Goodlet2 Previous studies have demonstrated that cefazolin can be safely used in patients with penicillin allergy labels; however, data on the safety of cefazolin use in patients with cephalosporin allergy labels remains limited.Reference Norvell, Porter and Ricco3,Reference De Luca, Vogrin and Holmes4 The purpose of this study is to investigate the incidence of immediate hypersensitivity reactions (HSRs) and SSIs with cefazolin compared to vancomycin or clindamycin in patients with cephalosporin allergy labels when used for perioperative prophylaxis.
Methods
This is a retrospective analysis of adults with a non-cefazolin cephalosporin allergy label who underwent a surgical procedure at Mayo Clinic between July 2022 and September 2022 and received perioperative prophylaxis with cefazolin, clindamycin, or vancomycin. Incidence of immediate HSRs and postoperative infections were determined using manual chart review. Patients were excluded if they were pregnant, incarcerated, received more than one perioperative antibiotic, received antibiotics for non-perioperative indications within 24 hours of the procedure, had a documented allergy label to cefazolin or ceftezole, or declined research authorization. The Mayo Clinic Institutional Review Board deemed this study to be exempt.
Cephalosporin allergy labels were classified as high risk (including Stevens-Johnson syndrome, toxic epidermal necrolysis, or multiorgan hypersensitivity response), moderate risk (including disseminated hypersensitivity or anaphylaxis), or low risk (including side effects/intolerances [gastrointestinal intolerance, headache, cough, hypertension, tinnitus, muscle aches, or neuropsychiatric disturbances], limited HSRs [self-limited cutaneous rash or itching], or nonspecific).Reference Sarfani, Stone, Murphy and Richardson5 For preexisting cephalosporin allergy labels, type-1 HSRs were defined as angioedema, edema, breathing difficulties, wheezing, urticaria, hives, or hypotension. For the primary outcome, immediate perioperative HSRs were classified as probable or possible. Probable immediate HSR we defined as the presence of acute hypotension, angioedema, bronchospasm, erythema, flushing, increased mechanical ventilator pressures, respiratory distress, urticaria, wheezing, or allergic reaction noted.Reference Grant, Song and Shajari6 Possible immediate HSR was determined by the administration of epinephrine and/or diphenhydramine, with doses and routes consistent with HSR treatment, on the day of surgery.Reference Grant, Song and Shajari6 Consideration for immediate HSR began when perioperative antibiotics were administered and continued for 60 minutes following the conclusion of surgery. SSIs were classified as superficial, deep, and organ space according to National Healthcare Safety Network surveillance requirements.Reference Christensen, Dowler and Doron7
Categorical data was summarized using total counts and percentages, and continuous data was summarized using means and standard deviations. To compare baseline characteristics and outcomes between groups, χ2 or Fisher’s exact tests were for categorical data, and Analysis of Variance for continuous data. All analyses were performed using SAS version 9.4 software (SAS Institute, Inc.; Cary, NC), and p-values ≤ .05 were considered statistically significant.
Results
A total of 406 surgical cases were included. Patient baseline characteristics were similar across the three groups, with a notable difference being the selection of perioperative antibiotic based on patient allergy type (Supplementary Table 1). Most patients who received cefazolin had allergy types that were classified as low risk, whereas patients with allergies classified as moderate or high risk were more likely to receive vancomycin or clindamycin.
No probable immediate HSR occurred. Possible immediate HSRs occurred in three (1.7%) cases where cefazolin was used, six (6.5%) cases with clindamycin, and seven (5%) cases with vancomycin perioperative prophylaxis (p-value = .12) (Table 1). There was one documented SSI, which occurred in a patient who had received vancomycin perioperatively.
Table 1. Outcomes
CZO, cefazolin; CLI, clindamycin; DPH, diphenhydramine; HSR, hypersensitivity reaction; SSI, surgical site infection; VAN, vancomycin.
The primary outcome was also assessed in a subgroup of 152 surgical cases for patients with a history of type-1 hypersensitivity to a cephalosporin. No possible or probable immediate HSRs occurred when cefazolin was used; however, 4 (9%) of cases where clindamycin was used and 4 (5%) of cases where vancomycin was used had a possible immediate HSR (P = .29).
Discussion
Among patients with cephalosporin allergy labels, the use of perioperative cefazolin was not associated with an increased risk of immediate HSR compared to clindamycin or vancomycin. This finding is consistent with previous studies of patients with penicillin allergy labels.Reference Bhathal, Joseph, Nailor and Goodlet2,Reference Norvell, Porter and Ricco3 It is logical given that cefazolin does not share an R-group side chain with any other beta-lactam antibiotics available in the United States.Reference Zagursky and Pichichero8,Reference Banerji, Solensky, Phillips and Khan9
Our cohort includes 173 surgical cases where cefazolin was given to patients with cephalosporin allergy labels, with an observed rate of possible immediate HSR lower than that for cases where clindamycin or vancomycin were used. Among these, cefazolin was used for 27 surgical cases for patients with a history of type-1 HSR to a cephalosporin, and no immediate HSRs were observed. The higher incidence of immediate HSR among cases where clindamycin or vancomycin was used, as compared to cefazolin, may be due to individuals with drug allergies being predisposed to having additional drug allergies regardless of any structural similarity between the drugs.10
Limitations of this study include its retrospective design and modest sample size. Our assessment of HSRs relied on documentation within the electronic medical record. HSRs observed may have been caused by perioperative medications other than the antibiotic. Use of corticosteroids could have muted potential HSRs to an antibiotic; however, corticosteroid administration was not different between groups.
Our results suggest that avoiding cefazolin for perioperative prophylaxis in patients with non-cefazolin cephalosporin allergy labels may not be warranted.
Supplementary material
The supplementary material for this article can be found at https://doi.org/10.1017/ash.2025.10221.
Acknowledgements
We thank Sara Varghese, PharmD for her contributions to the development of our research protocol.
Financial support
Publication of this study was funded by a research grant from the Mayo Midwest Pharmacy Research Committee.
Competing interests
All authors report no conflicts of interest relevant to the article.
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