Adverse Effects

While being associated with a low percentage of adverse reactions, the p-lactams are the most frequent source of troublesome allergic reactions among the antibiotics. The overall frequency of adverse effects associated with penicillin use is less than 10%, including allergic and other reactions. Anaphylaxis is a serious, rare allergic response with an occurrence rate between 0.004% and 0.015% of penicillin courses. Allergic reactions to penicillin are immediate immunoglobulin (Ig) E-mediated type I immune responses. Symptoms and signs of IgE-mediated reactions may include urticaria, pruritus, bronchospasm, angioedema, laryngeal edema, and hypotension. Late onset immune-mediated reactions to p-lactam antibiotics may manifest as eosinophilia, hemolytic anemia, interstitial nephritis, or serum sickness. In contrast to the rare allergic reactions, nonallergic p-lactam rashes are common. For example, ampicillin is associated with nonurticarial rashes in 5 to 10% of recipients.

The incidence of nonallergic ampicillin eruptions is 40 to 100% in patients with concomitant Epstein-Barr virus (mononucleosis), cytomegalovirus, acute lymphocytic leukemia, lymphoma, or reticulosarcoma. Non-allergic penicillin-associated rashes are characteristically morbilliform (symmetrical, erythematous, confluent, maculopapular) eruptions on the extremities. The onset of typical nonallergic eruptions is more than 72 hours after p-lactam exposure. The mechanism for the nonurticarial ampicillin rash is not known and is not related to IgE or type I hypersensitivity. Penicillin skin tests are not useful in the evaluation of nonurticarial ampicillin rashes. Patients with a history of nonurticar-ial ampicillin rashes may receive other p-lactam antibiotics without greater risk of subsequent serious allergic reactions.

Allergic cross-reactivity between p-lactam antibiotics is significant. The frequency of allergic reactions to another p-lactam antibiotic is 5.6% among patients with a history of IgE-mediated hypersensitivity to one p-lactam antibiotic plus positive results from a penicillin skin test. In general, patients with a convincing history of type I reaction to one p-lactam antibiotic should avoid all other p-lactam antibiotics except aztreonam. However, most patients give unreliable histories of penicillin allergy because of confusion with nonallergic penicillin rashes. Among patients who report penicillin allergies, 80 to 90% have negative results from penicillin skin tests, and 98% tolerate subsequent p-lactam antibiotic treatments. A careful history may discriminate between nonallergic reactions and true penicillin allergy and permit safe p-lactam therapy.

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