Impact of multimodal interventions on β-lactam use in patients with penicillin or cephalosporin allergy

PURPOSE: To evaluate the impact of multimodal interventions, including electronic cross-reactivity alert suppression, clinician education, and implementation of a β-lactam allergy guideline, on β-lactam prescribing in hospitalized adults with reported penicillin or cephalosporin allergy. METHODS: Single-center, retrospective pre-post study included adults (≥ 18 years) with documented penicillin or cephalosporin allergy. Patients were excluded if they received fewer than two antibiotic doses, died within 48 hours of admission, had allergies to both penicillins and cephalosporins, or received antibiotics solely for surgical prophylaxis. The primary outcome was penicillin or cephalosporin administration. Secondary outcomes included hospital length of stay, allergic reactions, Clostridioides difficile infections, and antimicrobial discontinuation due to adverse reaction. RESULTS: Among 234 patients included (pre-intervention n = 123; post-intervention n = 111), baseline demographics, Charlson Comorbidity Index, and allergy characteristics were similar between groups. Penicillin or cephalosporin use increased significantly following interventions (65% vs 81%, P = 0.006), while non-β-lactam use decreased (26.8% vs 14.4%, P = 0.020). There were no differences in duration of therapy, frequency of allergic reactions, hospital length of stay, 30-day C. difficile infection rates, or antimicrobial discontinuation rates due to allergy or intolerance. CONCLUSION: A bundled strategy combining guideline implementation and education with removal of β-lactam cross-reactivity alerts significantly increased penicillin and cephalosporin prescribing among adults with documented penicillin or cephalosporin allergies without increasing allergic reactions or other safety events. These findings support multimodal stewardship approaches to safely optimize β-lactam utilization in hospitalized patients with reported allergies.