Salkind AR, Cuddy PG, Foxworth JW (University of Missouri–Kansas City School of Medicine, Kansas City, MO) Antibiotics containing penicillin may be withheld from patients based on their self-reported history of an adverse reaction to penicillin. From 0.7% to 10% of the general population suffers some kind of adverse reaction to penicillin, with the severity depending on exposure history, route of administration, duration of treatment, time elapsed from reaction to diagnostic skin testing or repeat exposure, and type of initial reaction. Type I or immediate reactions show systemic manifestations of anaphylaxis and occur in 0.004% to 0.15% of penicillin courses, most often in adults aged 20 to 49 years. In these reactions, penicillin or its reactive metabolites bind covalently to serum proteins and cross-link with preformed penicillin-specific immunoglobulin E antibodies in mast cells or basophils. With cross-linking to allergen, mast cells release their mediators. Late reactions occur after 72 hours of drug administration and are termed types II, III, or IV. Skin testing reveals possible cross-reactivity in individuals with previous type I reactions, but this is less likely with the nonimmediate reactions. Unless rash develops, a serious reaction is unlikely, so penicillin can be given; other causes of rashes, such as viral or bacterial infections or other medications, must be ruled out. A cross-reactivity between cephalosporins and penicillins may occur, but most patients with penicillin allergy tolerate cephalosporins without significant reaction. Allergic reactions occurred within 24 hours of cephalosporin administration in 5.6% of patients with a penicillin allergy history and a positive skin test result and in 1.7% of patients with a penicillin allergy history and a negative skin test result. Based on 4 studies, the presence of a clinical history indicative of penicillin allergy increases the chance that skin testing will be positive, but the absence of such a history only decreases the likelihood of a positive skin test result by just over half. Patients with no clinical history of a type I penicillin reaction do not need to undergo a penicillin skin test, although elective testing has been suggested. An oral penicillin challenge may be administered to patients with positive penicillin allergy histories and negative skin tests; generally these patients will have a negative oral challenge test result and can receive penicillin. For patients with a history of penicillin allergy who require a cephalosporin, the likelihood that it was a type I reaction should be determined. If the history indicates that it is not a true penicillin allergy, the cephalosporin can be administered. Penicillin skin testing is indicated for a concerning history, with the cephalosporin given with a negative test and cephalosporin desensitization considered for a positive test if no other medication is feasible. Carbapenems should not be used for patients with a positive penicillin skin test or a concerning history of a type I allergic response to penicillin, but aztreonam is usually safe for use in these patients. Patients who have a negative response to the oral challenge test can safely receive penicillin in 98% of cases. Salkind and colleagues provide a nice review of penicillin allergy and how to approach patients who claim to have a penicillin allergy and require antibiotic therapy. The bottom line is that most patients reporting a history of penicillin allergy are not truly allergic.
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