The broadest experience with managing adverse drug reactions is with penicillin. Penicillin allergy should be evaluated when the individual is well and not in acute need of treatment. Penicillin skin testing is helpful for IgE-mediated reactions because of its negative predictive value; only 1% to 3% of patients with negative skin tests have a reaction, which is mild, when re-exposed to penicillin. Skin testing for penicillin should be performed using the major determinant, penicilloyl polylysine (available as Pre-Pen), and minor determinants, which include penicillin G, penicilloate, and penilloate. Skin testing to penicillin does not predict non-IgE-mediated reactions. For patients with a history consistent with serum sickness or desquamative-type reactions, skin testing should not be performed, and penicillin should be avoided indefinitely.
The risk of a child who has reacted positively to penicillinskin testing suffering an allergic reaction to a cephalosporinantibiotic is less than 2%. It is believed that the first-generation cephalosporins (e.g., cephalexin) are more likely thansecond-generation (e.g., cefuroxime) or third-generation (cefpodoxime) cephalosporins to be cross-reactive. This is dueto the chemical similarity of side chains of the β-lactam ringbetween penicillin and first-generation cephalosporins.
If penicillin skin testing is positive, penicillin should be avoided, and an alternative antibiotic should be used. If there is a definite need for penicillin, desensitization can be accomplished by administration of increasing amounts of drug over a short time in a hospital setting. The exact mechanism of desensitization is unclear; however, it is thought to render mast cells unresponsive to the drug. To maintain desensitization, the drug must be given at least twice daily. If the drug is stopped for longer than 48 hours, the patient is no longer desensitized, and the same protocol must be repeated before repeated antibiotic use.
For other antibiotics, the relevant allergenic determinants produced by metabolism or degradation are not well defined. Skin testing to the native antibiotic in nonirritating concentrations can be performed. A negative response does not exclude allergy; however, a positive response suggests the presence of IgE-mediated allergy. In the case of a negative skin test response, a graded challenge or test dose may be administered, depending on the clinical history of the reaction. Patients who have experienced Stevens-Johnson syndrome, toxic epidermal necrolysis, or serum sickness should not be challenged.
Anaphylaxis is the most serious complication of allergic drug reactions and can result in death (see Chapter 81).
Most drug reactions do not seem to be allergic in nature. Repeated, intermittent exposure during childhood or early adulthood contributes to an increased incidence of adverse drug reactions in adults.
Avoidance of the suspect drug is paramount. A MedicAlert bracelet with appropriate information should be worn. One of the most common concerns in regard to allergic drug reactions is cross-reactivity between penicillin and cephalosporins. In children with a history of penicillin allergy, it is important to determine whether they are truly allergic by skin testing to penicillin, using the major and minor determinants. If the penicillin skin test is negative, there is not an increased risk of an allergic reaction to cephalosporins. A positive penicillin skin test leads to an alternate non-cross-reacting antibiotic, a graded challenge to the required cephalosporin under appropriate monitoring, or desensitization to the required cephalosporin.