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Abstract

Introduction: Cross-reactivity may exist between carbapenems and Penicillin Allergy (PCN-A) due to structural similarities in these antibiotic classes. Evaluating the risk of carbapenem use in patients with PCN-A is challenging due to inconsistent study designs and outcomes, and small sample size. The purpose of this study was to more fully evaluate the risk of carbapenem use in patients with PCN-A. Hypothesis: Patients with PCN-A will have a higher incidence of carbapenem-related allergic reactions than those with No Known Drug Allergies (NKDA). Methods: This cohort study compared carbapenem-related reactions in patients with a history of PCN-A to patients with NKDA. To be a PCN-A patient, the PCN allergy had to be consistent with a true allergy, or required positive penicillin skin testing. The primary endpoint was an allergic reaction related to carbapenem use. A sample size of 1,600 total patients was calculated assuming a carbapenem reaction rate of 1% in those with NKDA providing 80% power to detect a 3 fold increase in carbapenem-related reactions in those with PCN-A. Results: PCN-A (N = 865) vs NKDA (N = 816) groups were similar in baseline characteristics with the exception of a higher proportion of males in the NKDA group. There were significantly more reactions with carbapenem use in PCN-A vs NKDA cohorts, 2.9% vs 0.25% (p < 0.0001). Within the PCN-A group 201 patients had a PCN-A consistent with anaphylaxis with 664 alternate reactions: carbapenem reaction rates 4% vs 2.6% respectively (p = 0.29). One of the 9 patients with positive penicillin skin testing had a carbapenem associated reaction. No reactions resulted in cardiopulmonary instability. Seven of the 25 reactions in PCN-A patients occurred on day 1 of therapy, 12 occurred on days 2 through 5, and the remaining 6 were further delayed. All reactions were characterized as a rash with the exception of 1 drug fever. Conclusions: A clinically significant increase in carbapenem-related reactions was observed in patients with PCN-A. Reactions to carbapenems were minor, but severe reactions cannot be excluded. These findings will help to inform health care provider’s decisions relating to the use of carbapenems in patients with PCN-A.