Patients With Nonanaphylactic Penicillin Allergy Are Not at Increased Risk of Allergic Events After Receiving Prophylactic Preoperative Cefazolin Prior to Closed Fracture Repair

Background The most commonly used prophylactic antibiotic for orthopaedic surgery is cefazolin. As the cefazolin molecule shares beta-lactam structural similarities with penicillin, it is common practice to avoid cefazolin administration to patients with penicillin allergy. We aimed to explore the risk of allergic reactions in patients with penicillin allergy who received cefazolin prophylaxis prior to fracture fixation surgery. Question/purpose In patients with nonanaphylactic penicillin allergy, is administration of cefazolin associated with increased risk of intraoperative adverse events (such as hypoxia, hypotension, or rash) when compared with administration of a different prophylactic antibiotic? Methods Between January 1, 2015, and December 31, 2019, we performed open reduction with internal fixation for 5169 closed fractures of the upper and lower extremities of the pelvis at our institution. Of those, we considered patients with self-reported nonanaphylactic penicillin allergies as potentially eligible for evaluation. After subject screening, 9% (452) of patients were eligible; a further 91% (4717) of patients were excluded because either they did not report penicillin allergy or they reported facial, tongue, and/or throat swelling; breathing difficulty; or anaphylactic shock after a previous administration of penicillin. We recorded antibiotic administered preoperatively and any intraoperative or immediate postoperative adverse events, including allergic reactions (rash, bronchospasm, facial edema), hypotension, respiratory depression, nausea, or other cardiac lability (such as new arrhythmia) or use of rescue medications (such as epinephrine, hydrocortisone, or diphenhydramine). Thirty-eight percent (173 of 452) of patients received preoperative antibiotic prophylaxis with cefazolin. Both groups of patients (cefazolin and non-cefazolin) were similar in sex, age, BMI, Charlson comorbidity index scores, smoking, and fracture location. Results In patients with a nonanaphylactic penicillin allergy, administration of cefazolin was not associated with an increased risk of intraoperative adverse events (cefazolin group 5% [9 of 173], no cefazolin group 4% [11 of 279], relative risk 1.32 [95% confidence interval (CI) 0.56 to 3.12]; p = 0.53); the results were no different when evaluating allergic events (cefazolin group 1% [2 of 173], no cefazolin group 1% [3 of 279], relative risk 1.08 [95% CI 0.18 to 6.37]; p = 0.94). Conclusion Administration of prophylactic cefazolin prior to operative repair of either closed appendicular or pelvic fractures in patients with penicillin allergy did not result in an increased adverse event incidence relative to those patients administered a different preoperative prophylactic antibiotic. With cefazolin still considered the most efficacious prophylactic antibiotic for prevention of infection after fracture fixation surgery, these results may indicate that surgical teams could consider administration of cefazolin to patients with penicillin allergy who do not claim a history of anaphylactic reaction to penicillin. Although a large RCT evaluating the safety of cefazolin administration in patients with penicillin allergy may not be feasible, more prospective cohort studies may yield further valuable information on this topic. Level of Evidence Level III, therapeutic study.