(A-261) Anaphylaxis Risk Across Cephalosporin Generations and Cefaclor: Insights from a Nationwide Case-Crossover Study (2011–2023)

Background: Cephalosporins, the second most prescribed antibiotics after penicillins, comprise multiple generations and inhibit bacterial cell wall synthesis in South Korea. Cefaclor is the leading cause of anaphylactic reactions in recent national compensation.

Objectives: To evaluate the association between the generation-specific use of cephalosporins and the risk of anaphylactic shock.

Methods: We conducted a case-crossover study in South Korea using national health insurance claims data from 2011 to 2023, focusing on the patients diagnosed with anaphylactic shock (defined by ICD-10: T78.2, T80.5, T88.6) during 2014-2023. We excluded patients who lacked linkage to health insurance eligibility data, had no records of medication use for conditions unrelated to anaphylaxis during the risk period, or were prescribed only intravenous fluids. The risk period was defined as the 3 days prior to the first diagnosis of anaphylactic shock (index date), and for each patient, we matched up to three control visits. The three most recent healthcare visits within 31 days prior to the index date, starting from January 2011 were designated as control visits, incorporating both the risk and 28-day refractory periods. The 3 days prior to each visit was defined as the control period. We compared the generation-specific use of cephalosporins with cefaclor during the risk and control periods. Using conditional logistic regression models, we computed the odds ratio (OR) for the association of anaphylactic shock with cephalosporins use adjusted for the potential confounders. Furthermore, we conducted a sensitivity analysis by redefining patients to include those diagnosed with anaphylaxis requiring hospitalization, emergency care, or intramuscular epinephrine.

Results: We identified 247,524 patients with anaphylactic shock during the risk period, and 739,214 of these patients were matched for the control period. Cephalosporin use was significantly associated with the risk of anaphylactic shock (OR: 1.27, 95% CI: 1.24–1.31). This association was consistent across generations: 1st generation (OR: 1.47, 95% CI: 1.39-1.56), 2nd generation (OR: 1.08, 95% CI: 1.04-1.11), including cefaclor (OR: 1.19, 95% CI: 1.15-1.24), 3rd generation (OR: 1.24, 95% CI: 1.18-1.30), and 4th generation (OR: 4.48, 95% CI: 2.45-8.21). Similar results were observed in the analysis with an altered definition of anaphylaxis.

Conclusions: The risk of anaphylaxis was found to be significantly associated with all generations of cephalosporins including cefaclor. Therefore, in clinical practice, it is imperative to exercise caution in antibiotic selection for high-risk anaphylaxis patients, providing comprehensive explanations of potential allergic reactions.