Non–β-Lactam Antibiotic Hypersensitivity Reactions

To analyze non–β-lactam antibiotic (NBLA) hypersensitivity reactions in children.

Children 0–18 years who had a suspected NBLA allergy and had a skin test, intravenous test, or oral challenge test at a tertiary pediatric hospital in Melbourne, Australia.

141 children who underwent a skin test, intravenous test, or oral challenge test from May 2011 to June 2018 were retrospectively identified through chart review. Detailed allergy histories were obtained at an outpatient clinic before admission for allergy testing. Patients were given a graded challenge protocol starting at 1/100th concentration initially of the maximum recommended dose, followed by 1/10th and then the max dose. Patients were observed for 3 hours and instructed to continue at home for 3–5 days.

17.4% (26 of 149) of those challenged orally or intravenously with NBLAs had positive results, with the highest for Trimethoprim–sulfamethoxazole (TMP-SMX) (32.6%, 15 of 46) and erythromycin (10.4%, 8 of 77). Ten of the 26 positive challenges produced signs of an immediate reaction. Of the 4 children who reported anaphylactic reactions on initial exposure, only 1 had a positive intradermal test to gentamicin and was not challenged, and the other 3 did not react upon re-challenge. The median time from initial reported allergic reaction to allergy evaluation was 1.9 (range 0.1–14.9) years.

Four of every 5 children with suspected NBLA allergy could be de-labeled. On average, patients waited almost 2 years to be re-challenged. Timely access to allergy evaluation to de-label these patients would help preserve first-line antibiotics.

This large retrospective study suggests that 4 of 5 children labeled with a non-β-lactam antibiotic allergy do not have a true allergy. TMP-SMX and macrolides were most likely to trigger a true allergic reaction. Some reactions upon re-challenge included severe symptoms such as shortness of breath and vomiting. Significant delay (up to 15 years) exists between initial reaction and re-evaluation, and timely access to re-evaluation would help reduce use of second-line antibiotics. This study was limited with regard to a single hospital location.