Single‐dose prolonged drug provocation test, without previous skin testing, is safe for diagnosing children with mild non‐immediate reactions to beta‐lactams

Abstract

Introduction: Mild non-immediate reactions (NIRs) to beta-lactams (BLs) are the most frequent manifestation of drug allergy in children. The diagnostic approach is complex as the utility of skin tests (STs) and lymphocyte transformation tests (LTTs) is controversial. Drug provocation test (DPT) is the gold standard, although no standardized protocols exist. We aimed to investigate the utility of DPT in a unique dose without previous STs, and LTTs in the diagnosis of NIRs to BLs in children. Methods:We prospectively evaluated children 0-14 years old referred to the Regional University Hospital of Málaga during 2017-2020 reporting NIRs to BLs. We performed a DPT with a unique dose followed by regular treatment at home. If positive, STs and LTTs were done after the reaction had disappeared. Results:We included 194 children, having 24 (12.4%) a positive DPT. The main culprit was AX (70.1%) followed by AX-clavulanic acid (CLV) (26.8%) and the main symptoms maculopapular exanthema (MPE) (49.5%) and delayed-urticaria (48.5%). A decrease (p = 0.013) in the interval of days between drug administration and onset of symptoms was observed in positive DPT compared with the original reaction (3.5 vs 6 days), with no differences in the overall percentage of MPE and delayed-appearing urticaria (p = 0.551). No severe reactions occurred during DPT. Moreover, STs were positive in 13.33% and LTTs in 52.9%. Conclusions:Single-dose DPT without previous STs is a safe and useful way to assess NIRs to BLs in children. LTT has shown to be useful, confirming a T-cell mechanism involved in these reactions.

New diagnostıc perspectives in the management of pediatrıc beta‐lactam allergy

“…Given the unreliability of self‐reported clinical history and the poor predictive value of skin tests, direct DPT procedures by skipping skin tests in appropriate patients are gaining acceptance as a safe and accurate delabeling strategy 2,35,36,41,42,49,50 . In fact, an increasing number of pediatric studies have challenged the guidelines by performing direct DPT without prior skin testing in mild NIRs to BLs 33,36,42,49,51,52 . In these studies, only 3.4%–14% of children with a history of mild NIR had a positive DPT and only mild reactions were reported after DPT, supporting the safety of this procedure in children.…”

Simplifying the drug provocation test in non‐immediate hypersensitivity reactions to amoxicillin in children: The experience of a tertiary care allergy unit

“…So far, in NIR to βLs, it seems to be safe to administer the first dose of antibiotic in a single dose. 20,24,[32][33][34] In our study, we fractionated the dose as recommended by the EAACI position paper. 5 As reported above, only one patient reacted 30 min after the first fractionated dose (1/10) with mild urticaria.…”

“…In addition, a prolonged DPT results in increased confidence in the future use of the same drug when compared with a single‐day DPT. On the other hand, a prolonged DPT is questioned because of its impact on the gut microbiota and the potential risk of increasing antibiotic resistance 1,3,8–24 . So far there is no agreement on the best protocol to be used that reaches the best compromise between safety, time consumption, and potential side effects.…”

“…In the literature, most of the studies focused on NIR report the results of graded DPTs using incremental doses of the antibiotics administered with different and non‐standardized protocols, 1,15,16,23,25–31 describing how most of the reactions occur after the last dose on the first day or on subsequent days of DPT at home (Table 1). Only a few studies use a single‐dose protocol for DPT 20,24,32–34 . Table 2 summarizes the few studies where the first dose was administered all at once.…”

Addressing beta‐lactam allergy: A time for action

“…9 These results have recently been confirmed in an European population of children. 10 Aside from the inconvenience and potential need for specialty assessment, for very low-risk patients, the use of skin testing would be expected to perform poorly considering their low pre-test probability of a reaction. Several other studies have demonstrated that a single or two-step direct ingestion challenge with penicillins such as amoxicillin is a safe and practical strategy to remove a label of penicillin allergy.…”