A combined risk modeling strategy for clinical prediction of beta-lactam allergies in children

Abstract

Background: Drug provocation test (DPT) without skin tests is increasingly recommended in the evaluation of children with low-risk beta-lactam (BL) allergies. However, risk definitions are unclear. Objective: The aim of this study was to compose a clinical predictive model that could identify the children at low risk who could safely undergo direct DPT. Methods: The clinical data of 204 children who underwent a full diagnostic algorithm for suspected BL allergy were analyzed. Clinical data were used to construct mathematical predictive model for confirmed BL allergies. A prospective new sample was used for external validation of the final model. Results: The presentations during the index reaction were anaphylaxis in 5.9% and cutaneous reactions in the majority. BL allergy was confirmed in 15.7% of suspected cases. A backward multiple logistic regression model showed that a family history of drug allergy (adjusted odds ratio [aOR], 5.52), anaphylaxis (aOR, 5.14), any atopic disease other than asthma (aOR, 4.38), and a reaction interval of 0‐6 hours during the index reaction (aOR, 5.32) were significantly associated with a confirmed BL allergy. A mathematical combined model based on these factors showed a sensitivity of 77.8% and a negative predictive value (NPV) of 94.3%. The validation study replicated sensitivity and NPV values of the main cohort. Conclusion: The risk definition in BL allergies should depend on population-specific predictive models, including a combination of significant risk factors rather than empiric risk approaches. This may help to accurately determinate children at low risk who may safely proceed to direct DPT.

The Role of Medical History and Allergic Tests in the Analysis of Antibiotic Allergy in the Pediatric Population

“…This percentage was lower than expected based on the majority of the current literature (>90%) [33,34]. However, there are also other studies that present percentages similar to our findings [35,36]. In our study, the population included a substantial proportion of high-risk children (37.5%), enhancing the probability of having genuine allergy to the examined antibiotic.…”

“…Family history has also been identified as a risk factor for positive testing in other studies [35,36,[40][41][42]. For instance, a recent study in Portugal discovered that a family history of antibiotic allergy was significantly more frequently reported in children with a positive OPT [42].…”

Predictive models and applicability of artificial intelligence-based approaches in drug allergy

“…Furthermore, the decision tree was also unable to accurately predict BL-allergy [35]. By combining univariate analysis and multiple LR, a combined model including a family history of drug allergy, anaphylaxis, any atopic disease other than asthma, a reaction interval of 0–6 h showed a sensitivity of 77.8%, and a negative predictive value of 94.3% in predicting BL-allergy in children, with these values being further replicated in a second cohort [36].…”

Approach for delabeling beta-lactam allergy in children

“…In addition, familiar history of drug allergy has been associated in some studies with more prevalence of confirmed BL allergy ( 31 , 59 , 63 ). Indeed, a recent study has created a mathematical model to identify children with low-risk BL allergies where a backward multiple logistic regression showed that a family history of drug allergy was significantly associated with a confirmed BL allergy ( 66 ).…”