Frequency of severe reactions following penicillin drug provocation tests: A Bayesian meta‐analysis

Cardoso-Fernandes, António; Blumenthal, Kimberly G.; Chiriac, Anca Mirela; Tarrio, Isabel; Afonso-João, David; Delgado, Luís; Fonseca, João; Azevedo, Luís Filipe; Sousa‐Pinto, Bernardo

doi:10.1002/clt2.12008

Cited by 22 publications

(16 citation statements)

References 128 publications

(745 reference statements)

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“…Only one child (0.8%) developed true anaphylaxis out of the 123 patients. This finding is consistent with previous studies showing a low probability of potentially life-threatening reactions during DPT (20). Of interest, this female patient had no history of a severe reaction during her previous exposure to the antibiotic that had been implicated.…”

Section: Discussionsupporting

confidence: 92%

Drug allergy evaluation in children with suspected mild antibiotic allergy

et al. 2022

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BackgroundAdverse antibiotic reactions caused by an immunological mechanism are known as allergic reactions. The percentage of reported antibiotic allergies is likely to differ from the one validated after a drug provocation test (DPT) with the culprit antibiotic. This study aimed to compare the percentage of children who were thought to be allergic to a certain antibiotic with those who have a true allergy, as confirmed by DPTs. We also validated Skin Prick Tests (SPTs) and Intradermal Tests (IDTs) by assessing their sensitivity and specificity, in diagnosing antibiotic allergies using DPT as the gold standard. Furthermore, we investigated epidemiological risk factors such as personal and family history of atopic disease and eosinophilia.MethodsChildren with a history of possible allergic reaction to an antibiotic underwent a diagnostic procedure that included: (1) Eosinophil blood count, (2) SPTs, (3) IDTs and (4) DPTs. The parameters were compared with Pearson's Chi-Square and Fisher's Exact Test. Several risk factors that were found significant in univariate analysis, such as personal and family history of atopic disease, and positive SPTs and IDTs were examined with multiple logistic regression analysis to see if they were related to a higher risk for a positive DPT.ResultsSemi-synthetic penicillin was the most common group of antibiotics thought to cause allergic reactions in this study. Overall, 123 children with a personal history of an adverse reaction to a certain antibiotic, were evaluated. In 87.8% of the cases, the symptoms had occurred several hours after administration of the culprit antibiotic. Both SPTs and IDTs had low sensitivity but high specificity. Moreover, they had a high positive predictive value (PPV). In contrast, eosinophilia was not recognized as a risk factor. Seventeen patients (13.8%) had a true antibiotic allergy, as confirmed by a positive DPT. A positive IDT was a strong predictor of a positive DPT, along with a positive personal and family history of atopy.ConclusionSPTs and IDTs are very reliable in confirming antibiotic allergy when found positive. A negative result of a SPT highly predicts a negative DPT. A positive IDT and a positive personal and family history of atopy were recognized as significant risk factors for antibiotic allergy.

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Section: Discussionsupporting

confidence: 92%

Drug allergy evaluation in children with suspected mild antibiotic allergy

et al. 2022

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“…Despite the limitations of our study, including its retrospective nature, small sample, and heterogeneous practices in participating clinics, we conclude that a positive BLA DPT should preferably be confirmed with a second DPT conducted within a few weeks or months. Since positive DPT rates for BLA are low, and reactions observed are rarely severe, 21 the excess work required to repeat the DPT may be largely compensated by the higher diagnostic accuracy and the potential for removing a false label and averting its negative consequences. Placebo-controlled tests may be a rare and last resort when the DPT is repeatedly inconclusive or a nocebo effect is suspected.…”

Section: Discussionmentioning

confidence: 99%

Positive drug provocation with beta-lactam antibiotics in children: A single test may not be enough

Moral

Latorre

Toral

et al. 2022

Allergol Immunopathol

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Background: Drug provocation tests (DPTs) are considered the gold standard for diagnosing betalactam allergy. However, positive results tend to be mild and difficult to interpret. This study aimed to describe pediatric patients with a presumedly positive or inconclusive DPT, assess the decision to repeat the DPT, and describe its outcome. Methods: Retrospective review of all presumedly positive or inconclusive DPTs performed in six pediatric allergy clinics from 2017 to 2019. We describe the interpretation of results, focusing on the decision to repeat the DPT and its outcome. Results: Of 439 children challenged with a betalactam, 26 (5.9%) with a presumedly positive or inconclusive result were included in this study. Most were girls (n = 16, 61.5%), and the median age was 5 years (range 1–13). The initial DPT used amoxicillin (n = 13, 50.0%), amoxicillin-clavulanic acid (n = 12, 46.2%), or cefadroxil (n = 1, 3.8%). Reactions were early (n = 11, 42.3 %), delayed (n = 14, 53.8 %), or not registered (n = 1, 3.8 %), but mild in all cases. A second confirmatory DPT was proposed in 19 patients (73.1%) and performed in 17 patients (65.4%). Nine DPTs were performed from 1 day to 4 months after the first DPT, and the remaining eight took place 6 months to 2 years later. Fifteen children tolerated the drug in the second DPT: 88.2% of those reevaluated and 57.5% of the whole study group. Conclusion: The positive predictive value of DPT may be lower than expected. Given the mildness of observed reactions, a second confirmatory DPT is warranted within a few weeks or months.

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“…Severe reactions upon DCTs are exceedingly rare; in one meta-analysis of 112 studies including 26 595 participants, severe reactions occurred in just 0.06% and most severe reactions were anaphylaxis. 50 The majority of allergies with well documented histories and records can be reliably ruled out and DCTs can be done with a full dose of the antibiotic. Before developing new diagnostic tools, ex vivo or in vitro , it is necessary to define the patients for whom a full challenge can be safely done since these patients may not need any form of pre-intervention diagnostic.…”

Section: How Is Penicillin Allergy Diagnosed?mentioning

confidence: 99%

Improving antimicrobial stewardship with penicillin allergy testing: a review of current practices and unmet needs

Mabilat

Gros

Belkum

et al. 2022

JAC-Antimicrobial Resistance

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Penicillin allergy, the most frequently reported drug allergy, has been associated with suboptimal antibiotic therapy, increased antimicrobial resistance, increased rates of Clostridioides difficile colonization and infection, as well as extended hospital length of stay and increased cost. Although up to 10% of all patients may report penicillin allergy, most penicillin allergies are not confirmed. As such, most patients with a penicillin allergy can still safely use penicillin and related drugs following a more precise assessment. Herein, we review the current practices and unmet needs in penicillin allergy testing. The diagnostic algorithm is mostly based on a clinical history assessment followed by in vivo testing, i.e. skin test and/or drug challenge. As these tests are labour and resource intensive, there is increased interest in point-of-care penicillin allergy de-labelling solutions incorporated into Antimicrobial Stewardship Programmes including digital assessment tools. These can be locally parameterized on the basis of characteristics of target populations, incidence of specific allergies and local antibiotic usage to perform clinical risk stratification. Safely ruling out any residual risk remains essential and in vivo drug challenge and/or skin testing should be systematically encouraged. Gradual understanding and convergence of the risk stratification of the clinical presentation of penicillin allergy is enabling a wider implementation of this essential aspect of antimicrobial stewardship through digitalized decision tools and in vivo testing. More research is needed to deliver point of care in vitro diagnostic tools to democratize this de-labelling practice, which would be highly beneficial to patient care. This progress, together with better education of patients and clinicians about the availability, efficacy and safety of penicillin allergy testing, will increase the dissemination of penicillin allergy assessment as an important component of Antimicrobial Stewardship Programmes.

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Frequency of severe reactions following penicillin drug provocation tests: A Bayesian meta‐analysis

Cited by 22 publications

References 128 publications

Drug allergy evaluation in children with suspected mild antibiotic allergy

Drug allergy evaluation in children with suspected mild antibiotic allergy

Positive drug provocation with beta-lactam antibiotics in children: A single test may not be enough

Improving antimicrobial stewardship with penicillin allergy testing: a review of current practices and unmet needs

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