Most Children Safely Reuse Antibiotics 5 Years After Allergy Delabeling

A 5-year follow-up study found that antibiotic allergy delabeling in children is safe and effective in the long term, with 76.4% of children reusing the previously avoided antibiotics without significant adverse events.1

“More than three-quarters of delabeled children reused the drug without any significant issues, and no clinical reactions,” wrote study investigator Nikolaos Kitsos, MD, PhD, from the University of Thessaly in Greece, and colleagues.1

Up to 20% of the US population carries an antibiotic allergy label; however, many of these cases reflect reactions from viral rashes or other benign conditions rather than true allergies.2 Mislabeling results in significant consequences, such as avoiding first-line antibiotics, more treatment costs, using broad-spectrum alternatives, longer illness, and contributing to the global problem of antimicrobial resistance.1

A negative drug provocation test gives clinicians confidence to safely lift the antibiotic allergy label. Although drug provocation tests are validated for safety and accuracy in clinical trials, little is known about their long-term real-world reliability. Additionally, limited data exists on whether individuals actually reuse the once-avoided antibiotics after delabeling and whether new reactions occur.

Investigators addressed these questions in a 5-year follow-up study of 106 children (mean age, 8.3; range, 3 – 15 years) who had undergone antibiotic allergy evaluation and delabeling at a tertiary pediatric allergy center.1 Antibiotic allergy evaluation was a comprehensive assessment including detailed history, skin testing, and a drug provocation test following EAACI/ENDA protocols.

Clinicians informed families, both verbally and in writing, that their children could safely use the previously suspected antibiotic. About 5 years later, investigators reached out through structured interviews during clinic visits or by telephone, asking whether families had reused the delabeled antibiotic, who prescribed it, for what indication, whether any adverse events occurred, and whether they administered antihistamines. They also asked families to explain any decision not to reuse the antibiotic.

Among the 106 delabeled children, 81 (76.4%) reused the previously suspected antibiotic at least once in the 5-year follow-up, with most prescribed from primary care pediatricians (89%). In 18% of cases, parents took initiative and influenced pediatricians’ decisions.

Most prescriptions were for common childhood infections, such as otitis media and respiratory tract infections. Children most often reused penicillins (57%), followed by macrolides (24%) and cephalosporins (19%). On average, it took 5 years from testing to reuse antibiotics.1

It was rare for children to experience adverse events following reuse. Three children reported mild cutaneous reactions, including transient urticaria in 2 children and non-pruritic erythematous rash in 1 child, which appeared within 48 hours of initiating treatment and resolved spontaneously without requiring medication or discontinuation. These reactions resembled or were milder than the initial symptoms that led to the allergy referral.

“Although resensitization cannot be completely excluded because re-testing was not performed, the clinical course and ability to complete the antibiotic course without complications strongly suggest that these were not true allergic reactions, but likely coincidental or related to underlying illness,” investigators wrote.1

Investigators noted that 9 families reported giving prophylactic antihistamines during antibiotic administration, though this was mostly due to parental anxiety and not the physician’s recommendation. This showed that parents continue to have persistent concerns about recurrence, despite negative testing and formal delabeling.

Among the sample, 25 children (23.6%) did not reuse the antibiotic and cited reasons included parental anxiety (n = 12), absence of clinical need for that particular drug (n = 11), and physician’s reluctance (n = 2).1

“The latter is particularly notable as it indicates that some healthcare providers may still lack confidence in allergy testing results, highlighting a knowledge gap that needs to be confronted,” investigators wrote.1

The study ultimately demonstrated that negative drug provocation tests predict long-term tolerance of antibiotics in real-world settings, with more than three-quarters of delabeled children being able to reuse the drug.

“To fully realize the benefits of delabeling, health systems must address behavioral barriers through targeted education and reassurance for families and clinicians,” investigators concluded.1 “By delabeling and reducing unnecessary avoidance of beta-lactams and other first-line drugs, we contribute to antimicrobial stewardship, confronting bacterial infections and subsequently improving the overall healthcare.”

References

1. Kitsos N, Mavroudi A, Grivea I, Cassimos D. Once Allergic, Now Not: Do Children Use Delabeled Antibiotics?-A 5-Year Follow-Up Study. Acta Paediatr. Published online October 7, 2025. doi:10.1111/apa.70340

2. Plager J, Cutrer WB. Not a Benign (Mis)Label: Penicillin Allergy Education for the Nonallergist. MedEdPORTAL. 2024 Sep 27;20:11440. doi: 10.15766/mep_2374-8265.11440. PMID: 39347473; PMCID: PMC11427523.