“Reducing Alert Fatigue, Improving Patient Care” – Evaluating the Use of Cephalosporins After Removing a Cross-Allergenicity Alert

Reviewed by: David Cluck, PharmD; East Tennessee State University

Zimmer and colleagues evaluated cephalosporin utilization in those with documented intermediate-, high-, and severe-risk allergies following an EHR cross-reactivity alert removal.1 

This was a retrospective, observational, quasi-experimental review of patients with a documented intermediate-, high-, or severe-risk penicillin (PCN) allergy who received at least one dose of a systemic antibiotic for an indication in which a cephalosporin was considered first-line. The primary outcome was the rate of cephalosporin utilization. Secondary outcomes included rates of PCN utilization, antibiotic adverse effects, and a composite of treatment failure. Cephalosporin utilization significantly increased after alert removal (27% vs 67%, P < 0.001). Use of cefazolin increased by 47% (P < 0.001), while use of alternative agents, clindamycin and vancomycin, decreased by 12.5% (P = 0.032) and 13.4% (P = 0.021), respectively. The increase in cephalosporin use observed in the post-intervention group was significantly greater among those receiving antibiotics for SSI prophylaxis compared to other indications.  

Limited data exist regarding use of cephalosporins in patients with documented intermediate-, high-, or severe-risk allergies (e.g., anaphylaxis and non-IgE-mediated reactions). This study demonstrated that removal of an EHR cross-reactivity alert allowed for cephalosporins to be safely used in patients with intermediate and high-risk PCN allergies. Notably, there was not an increase in cephalosporin use in patients categorized to have severe-risk allergies which would include patients with Stevens-Johnson syndrome or toxic epidermal necrolysis. The general findings of this study are reinforced by a larger dataset which also found increased use of cephalosporins after modifying penicillin allergy EHR alerts. 

References:

  1. Zimmer A, Zagari J, Sudnik P, Yamshchikov A, Lopa S, Spitznogle S, DePasquale W, Donnelly D, Dobrzynski D, Stern J, Shulder S, Quartuccio KS. Cephalosporin use and patient outcomes following removal of penicillin-cephalosporin cross-reactivity alerts from the electronic health record. Antimicrob Agents Chemother. 2026 Jun 3;70(6):e0182025. 
  2. Macy E, McCormick TA, Adams JL, Crawford WW, Nguyen MT, Hoang L, Eng V, Davis AC, McGlynn EA. Association Between Removal of a Warning Against Cephalosporin Use in Patients With Penicillin Allergy and Antibiotic Prescribing. JAMA Netw Open. 2021 Apr 1;4(4):e218367.