Overdiagnosis of antibiotic allergy in children is a common and persistent challenge. Between 5% and 10% of children are labelled as allergic to antibiotics, most commonly beta-lactams, during early life. However, allergy evaluation, including drug provocation testing (DPT), confirms true allergy in only a small fraction of these cases. The majority of suspected reactions are non-allergic, often related to viral rashes or other benign conditions. Mislabeling leads to significant clinical consequences, including avoidance of first-line antibiotics, increased use of broad-spectrum alternatives, greater treatment costs, prolonged illness and a contribution to the global problem of antimicrobial resistance 1. DPT is regarded as the gold standard for the diagnosis of antibiotic allergy. When negative, DPT provides strong evidence for tolerance, allowing clinicians to safely remove the allergy label. Although the immediate safety and predictive accuracy of DPT have been established in controlled environments, less is known about long-term real-world outcomes. Specifically, there is limited evidence on whether families and clinicians actually reuse the previously avoided antibiotics after delabeling and whether any new adverse reactions occur. This knowledge gap is particularly important because the ultimate benefit of allergy delabeling depends on successful reuse in clinical practice 1. In this study, we performed a 5-year follow-up of children who had undergone antibiotic allergy evaluation and delabeling at a tertiary paediatric allergy centre. Between 2017 and 2020, 123 children were referred for suspected antibiotic allergy. After comprehensive assessment, including detailed history, skin testing and DPT following EAACI/ENDA protocols, 17 children (13.8%) were confirmed allergic and excluded from further analysis. The remaining 106 children (86.2%) had negative DPTs and were formally delabeled. These families received verbal and written confirmation that the previously suspected antibiotic could be safely used. Approximately 5 years later, families were contacted through structured interviews during clinic visits or by telephone. We asked whether the delabeled antibiotic had been reused, who prescribed it, for what indication, whether any adverse reactions occurred and if antihistamines were used. Families were also asked why the antibiotic had not been used, if applicable 2. Of the 106 delabeled children, 81 (76.4%) reused the previously suspected antibiotic at least once during the follow-up period. Prescriptions were most often for common childhood infections such as otitis media and respiratory tract infections. The majority of prescriptions were from primary care paediatricians (89%), with smaller contribution from emergency physicians, whereas parents were taking the initiative and influencing paediatrician decisions in 18% of cases. The most frequently reused antibiotic was penicillins (57%), followed by macrolides (24%) and cephalosporins (19%). The median time from allergy testing to reuse was 5 years (Table 1). Male: 58.5% Female: 41.5% Penicillins: 57% Macrolides: 24% Cephalosporins: 19% Adverse events following reuse were uncommon. Only three children (3.7%) reported mild cutaneous reactions: two presented with transient urticaria and one developed a non-pruritic erythematous rash. All reactions appeared within 48 h of initiating treatment, did not require medication or discontinuation of the antibiotic, and resolved spontaneously. Importantly, these symptoms were similar or milder compared to the initial suspected reactions that prompted allergy referral. None of these children required hospitalisation or additional medical care. 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. Interestingly, nine families (11.1%) reported giving prophylactic antihistamines during antibiotic administration, mostly due to parental anxiety rather than physician's recommendation. This behaviour reflects persistent concerns about recurrence, even after negative testing and formal delabeling. Among the 25 children (23.6%) who did not reuse the antibiotic, reasons included ongoing parental anxiety (n = 12), absence of clinical need for that specific drug (n = 11), and physician's reluctance (n = 2). 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. This study adds important evidence by demonstrating that negative DPTs predict long-term tolerance of antibiotics in real-life settings. More than three-quarters of delabeled children reused the drug without any significant issues, and no clinical reactions. Mild reactions occurred rarely, were self-limited and not related to the antibiotic, reinforcing the safety of delabeling protocols. These findings align with existing literature but extend our understanding by providing one of the longest follow-up periods reported to date for paediatric antibiotic allergy delabeling 3, 4. However, the data also highlight barriers that remain even after successful delabeling. Psychological factors, such as fear of recurrence and residual anxiety from past experiences, appear to influence parental decisions. Similarly, occasional hesitation among primary care physicians demonstrates the need for broader dissemination of guidelines and education about the predictive value of negative DPT. Practical strategies to overcome these barriers may include providing families with written documentation of test results, reinforcing messages during follow-up visits, and improving communication between allergists and primary care providers. Integration of allergy testing outcomes into electronic health records could further enhance clinician confidence and prescribing practices 5. Our study is not without limitations. Data were collected from parental reports, which may introduce recall bias. Additionally, the study was conducted at a single tertiary centre, potentially limiting generalizability. Nevertheless, the five-year follow-up, structured methodology, and inclusion of real-world prescribing behaviour, provide valuable insights that strengthen the case for widespread implementation of delabeling programs. In summary, antibiotic allergy delabeling is a safe and effective strategy that can restore access to first-line antibiotics for most children. Negative DPT remains a reliable predictor of tolerance, even several years later. Most children reused delabeled antibiotics without problems, and mild reactions were rare and clinically insignificant. To fully realise the benefits of delabeling, health systems must address behavioural barriers through targeted education and reassurance for families and clinicians. 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. The authors declare no conflicts of interest. Research data is not shared.
Kitsos et al. (Tue,) studied this question.
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