Antibiotic Allergy in Pediatrics

Abstract

The overlabeling of pediatric antibiotic allergy represents a huge burden in society. Given that up to 10% of the US population is labeled as penicillin allergic, it can be estimated that at least 5 million children in this country are labeled with penicillin allergy. We now understand that most of the cutaneous symptoms that are interpreted as drug allergy are likely viral induced or due to a drug-virus interaction, and they usually do not represent a long-lasting, drug-specific, adaptive immune response to the antibiotic that a child received. Because most antibiotic allergy labels acquired in childhood are carried into adulthood, the overlabeling of antibiotic allergy is a liability that leads to unnecessary long-term health care risks, costs, and antibiotic resistance. Fortunately, awareness of this growing burden is increasing and leading to more emphasis on antibiotic allergy delabeling strategies in the adult population. There is growing literature that is used to support the safe and efficacious use of tools such as skin testing and drug challenge to evaluate and manage children with antibiotic allergy labels. In addition, there is an increasing understanding of antibiotic reactivity within classes and side-chain reactions. In summary, a better overall understanding of the current tools available for the diagnosis and management of adverse drug reactions is likely to change how pediatric primary care providers evaluate and treat patients with such diagnoses and prevent the unnecessary avoidance of antibiotics, particularly penicillins.

FIGURE 1

Penicillin-cephalosporin cross-reactivity based on side-chain similarity. Penicillin G, benzylpenicillin; penicillin VK, phenoxymethylpenicillin potassium. Approximately 2% of penicillin allergic patients would be expected to react to a cephalosporin, however this number may exceed 30% when administered cephalosporins with identical R1 side chains. Cefditoren and cefpodoxime are oral cephalosporins with the same side chain.

FIGURE 2

First-generation cephalosporin cross-reactivity. Approximately 2% of penicillin allergic patients would be expected to react to a cephalosporin, however this number may exceed 30% when administered cephalosporins with identical R1 side chains. Cefditoren and cefpodoxime are oral cephalosporins with the same side chain.

FIGURE 3

Second-generation cephalosporin cross-reactivity. Approximately 2% of penicillin allergic patients would be expected to react to a cephalosporin, however this number may exceed 30% when administered cephalosporins with identical R1 side chains. Cefditoren and cefpodoxime are oral cephalosporins with the same side chain.

FIGURE 4

Third-, fourth-, and fifth-generation cephalosporin cross-reactivity. Approximately 2% of penicillin allergic patients would be expected to react to a cephalosporin, however this number may exceed 30% when administered cephalosporins with identical R1 side chains. Cefditoren and cefpodoxime are oral cephalosporins with the same side chain.

FIGURE 5

Third-, fourth-, and fifth-generation cephalosporin cross-reactivity (continued). Approximately 2% of penicillin allergic patients would be expected to react to a cephalosporin, however this number may exceed 30% when administered cephalosporins with identical R1 side chains. Cefditoren and cefpodoxime are oral cephalosporins with the same side chain.

FIGURE 6

Stepwise approach to the evaluation and treatment of patients with type I IgE-mediated drug allergy (see Table 1). This approach cannot be used in the case of severe reactions, including SJS, TEN, DRESS syndrome, nephritis, hepatitis, and hemolysis. Adapted from Turvey SE, Cronin B, Arnold AD, Dioun AF. Antibiotic desensitization for the allergic patient: 5 years of experience and practice. Ann Allergy Asthma Immunol. 2004;92(4): p. 430 and Dioun AF. Management of multiple drug allergies in children. Curr Allergy Asthma Rep. 2012;12(1): p. 81. See Figs 1–5 for cross reactivity. ^aPursuing skin testing is dependent on negative predictive value of testing and reagent dependent. Consider going straight to challenge if reaction was mild and inconsistent with IgE mediated drug allergy. ^b Consider graded challenge for milder reactions or desensitization for more severe reactions. ^cConsider graded challenge for milder reactions. ^dConsider desensitization regardless of skin test, particularly if index reaction was severe.