Beta-lactam Allergy In Children Research Articles

Approach for delabeling beta-lactam allergy in children.

A considerable number of pediatric patients treated with beta-lactam (BL) antibiotics develop delayed onset of skin rashes during the course of treatment. Although the most frequent cause of these symptoms is infectious, many cases are labeled as allergic reactions to these drugs. BL allergy labels could have a negative impact, as they imply avoidance of this group of drugs and the use of second-line antibiotics, leading to a potential increase in adverse effects and the utilization of less effective therapies. This constitutes a major public health concern and economic burden, as the use of broad-spectrum antibiotics can result in multidrug-resistant organisms and prolonged hospital stays. Therefore, it is crucial to delabel patients during childhood to avoid false labeling in adult life. Although the label of BL allergy is among the most frequent causes of allergy referral, its management remains controversial, and new diagnostic perspectives are changing the paradigm of managing BL allergies in children. Traditionally, drug provocation testing (DPT) was exclusively performed in patients who had previously obtained negative results from skin tests (STs). However, the sensitivity of STs is low, and the role of in vitro testing in the pediatric population is not well defined. Recent studies have demonstrated the safety of direct DPT without prior ST or serum tests for pediatric patients who report a low-risk reaction to BLs, which is cost-effective. However, there is still a debate on the optimal allergic workup to be performed in children with a benign immediate reaction and the management of children with severe cutaneous adverse drug reactions. In this review, we will discuss the impact of the label of BL allergy and the role of the different tools currently available to efficiently address BL allergy delabeling in children.

Risk Factors of Challenge-Proven Beta-Lactam Allergy in Children with Immediate and Non-Immediate Mild Cutaneous Reactions

Introduction: Beta-lactam (BL) antibiotics are the most often involved drugs in allergic reactions. Mild cutaneous reactions such as maculopapular exanthema or urticaria are the most common presenting complaints of BL allergy in the pediatric population. However, it can be challenging to distinguish BL-induced allergy from reactions due to infections or other reasons. In this study, we aimed to determine the clinical characteristics and potential risk factors of true BL allergy in children with suspected mild cutaneous reactions to BLs. Methods: We evaluated children who were admitted to our pediatric allergy clinic with suspected BL allergy in between January 2015 and March 2020. Patients with a history suggestive of immediate and non-immediate mild cutaneous reactions were included in the study. The oral challenge test (OCT) with the culprit drug was performed on all patients to confirm the diagnosis. Results: Two hundred fourteen (119 male and 95 female) patients with a median age of 4.9 years were evaluated. BL allergy was confirmed in 10.7% (23) of the patients, according to the OCT results. Most of the proven allergic reactions were of the immediate type (73.9%), and urticaria was the most common presenting complaint (60.8%) in proven BL-allergic patients. The negative predictive value of penicillin-G skin testing was 89.7% for immediate-type penicillin allergy and 93.4% for non-immediate reactions. Also, positive predictive value of penicillin-G skin testing was 50% for immediate and 25% for non-immediate reactions. In the multivariate logistic regression analysis, a history of proven drug allergy (Exp (B): 7.76, 95% CI: 1.88–31.97, p = 0.005) was found to be the risk for BL allergy. Conclusion: This study highlighted that OCTs should be performed to confirm the diagnosis in patients suspected of immediate and non-immediate mild cutaneous reactions to BLs and remove the overestimated “BL allergy” label. In these patients, a history of proven drug allergy might be a risk factor for true BL allergy.

Beta-lactam allergy and drug challenge test in children: a systematic review and meta-analysis.

Most cases of beta-lactam allergy in children are likely to be mislabeled. This study aimed to assess the prevalence of true positives, as determined by drug challenge tests, and the rate of false negatives in children with suspected allergies and confirm the safety of the drug challenge test. We conducted a systematic review and meta-analysis according to established procedures. Study participants were children with suspected beta-lactam allergy who underwent a drug challenge. PubMed MEDLINE, Dialog EMBASE, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and clinicaltrials.gov were searched from inception until March 5, 2021. The pooled prevalence of (a) positive results in the first challenge was 0.049 (95% CI, 0.041-0.057; I2 = 71%) from 78 studies; (b) serious adverse events was 0.00 (95% CI, 0.00-0.00; I2 = 0.0%) from 62 studies; and (c) positive results in the second challenge after the first negative result was 0.028 (95% CI, 0.016-0.043; I2 = 38%) from 18 studies. The prevalence of children with suspected beta-lactam allergy with true-positive results and false-negative results from the drug challenge test was very low. Serious adverse events resulting from drug challenge tests were also very rare. Most children with suspected beta-lactam allergy were likely to be mislabeled. Serious adverse events caused by the drug challenge test were rare. Few false-negative results were obtained from the drug challenge test.

New diagnostıc perspectives in the management of pediatrıc beta-lactam allergy.

Since overdiagnosis of beta-lactam (BL) allergy is common in the pediatric population, delabeling is a critical part of antimicrobial stewardship. Undesirable consequences of inaccurate BL allergy labeling can be handled by incorporating traditional delabeling or newer risk-based strategies into antibiotic stewardship programs. Conventional assessment of BL allergy relies upon a stepwise algorithm including a clinical history with skin testing followed by drug provocation tests (DPTs). However, a growing number of studies highlighted the suboptimal diagnostic value of skin testing in children. Recently, there has been a paradigm shift in the practice of BL allergy assessment due to recent challenging data which emphasize the safety and accuracy of direct DPTs in children with a suspicion of non-immediate mild cutaneous reactions such as maculopapular eruption, delayed urticaria, and possibly also for benign immediate reactions such as urticaria/angioedema. Identifying low-risk BL allergy patients, in whom skin tests can be skipped and proceeding directly to DPTs could be safe, has become a hot topic in recent years. New risk stratification and predictive modeling studies that have the potential to better predict BL allergy risk status have recently been introduced into the field of drug allergy, particularly in adults. However, in contrast to adults, risk assessment studies in children are rare, and optimal risk definitions are controversial. In the coming years, promising potential methods to elucidate the predictors of BL allergy in children will require multidimensional approaches that may include predictive analytics, artificial intelligence techniques, and point-of-care clinical decision tools.

An EAACI Task Force report on allergy to beta-lactams in children: Clinical entities and diagnostic procedures.

Beta-lactam (BL) allergy suspicion is common in children and constitutes a major public health problem, with an impact on patient's health and on medical costs. However, it has been found that most of these reactions are not confirmed by a complete allergic workup. The diagnostic value of the currently available allergy tests has been investigated intensively recently by different groups throughout the world. This has led to major changes in the management of children with a suspected BL allergy. Particularly, it is now well accepted that skin tests can be skipped before the drug provocation test in children with a benign non-immediate reaction to BL. However, there is still a debate on the optimal allergic workup to perform in children with a benign immediate reaction. In addition, management of children with severe cutaneous adverse drug reactions remains difficult. In this review, based on a selection of the most relevant studies found in the literature, we will review and discuss the diagnosis of different forms of BL allergy in children.

The negative predictive value of 5-day drug provocation test in nonimmediate beta-lactam allergy in children

BackgroundExtending the drug provocation test (DPT) period is recommended for patients with suspected nonimmediate beta-lactam antibiotic (BLA) allergy and negative DPT. No consensus has been reached regarding the duration of prolonged provocation. ObjectiveWe aimed to determine the negative predictive value (NPV) of the 5-day extended DPT. MethodsParents of patients with suspected nonimmediate mild cutaneous reactions with BLAs who had been subjected to 5-day DPT with culprit drugs were questioned by telephone interview about reexposure to the tested drug. Patients with reported reaction during reexposure were reevaluated. Skin tests and serum-specific immunoglobulin E (IgE) analysis were not performed before first DPT. ResultsA total of 355 patients had negative results in 5-day DPT. The median age at DPT was 4.2 years, and 52.9% were male. The families of 255 patients (72%) could be contacted. Of these 255 patients, 179 (70%) had used the same drug, and reactions were reported for 6 (3.4%) of those patients, who were subsequently reevaluated. Five of the 6 patients had DPT with amoxicillin-clavulanate and 1 with cefixime. When detailed history was taken, 2 of the 5 patients with amoxicillin-clavulanate reaction were found to have used the drug unintentionally after their reaction to reexposure and did not have any symptoms. One of the patients underwent allergy workup and tested negative, and the other 2 refused the test. The patient with reported cefixime reaction underwent repeated allergy workup and tested negative. Therefore, the NPV of 5-day prolonged DPT was 98.9%. ConclusionThe 5-day prolonged DPT has high NPV and seems appropriate in duration for children with suspected nonimmediate-BLA allergy.

Hypersensitivity reactions to beta-lactams in children.

To present the most recent evidence on beta-lactam hypersensitivity reactions in children. Drug provocation tests (DPTs) are the gold standard when investigating beta-lactam allergy in children and evidence is increasingly supporting DPTs without skin tests as a safe approach when evaluating children with nonimmediate mild reactions to beta-lactams. Of note, data are limited in the adolescent population, and this attitude may not apply to this age group. Standardization of DPT protocols is required in nonimmediate reactions, as many protocols ranging from 1 to 10 days have been described. The optimal duration of DPT is still unknown, with extended protocols providing slightly more sensitivity and possible higher long-term compliance, at the expense of potential side effects associated with prolonged antibiotic use. On the other hand, 1-day DPTs will identify the vast majority of patients, and the rest will only develop a mild rash during a subsequent full treatment. The natural history of beta-lactam allergy in children is not well studied with recent evidence pointing to the resolution of most confirmed beta-lactam allergies after 3 years. Further studies are needed for the standardization of DPT protocols and to confirm the favourable natural history of beta-lactam drug allergies in children. In addition, multicentric studies are required to confirm the increasingly accepted position of performing DPTs without skin tests in nonimmediate mild reactions to beta-lactams and to further evaluate the possibility of performing DPTs in benign immediate reactions to beta-lactams in children.

The Investigation of Suspected Beta-Lactam Allergy in Children; Comparison of Contemporary Clinical Practice By International Specialists

The Investigation of Suspected Beta-Lactam Allergy in Children; Comparison of Contemporary Clinical Practice By International Specialists

Management of allergy to penicillins and other beta-lactams.

The Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI) and an expert panel have prepared this guidance for the management of immediate and non-immediate allergic reactions to penicillins and other beta-lactams. The guideline is intended for UK specialists in both adult and paediatric allergy and for other clinicians practising allergy in secondary and tertiary care. The recommendations are evidence based, but where evidence is lacking, the panel reached consensus. During the development of the guideline, all BSACI members were consulted using a Web-based process and all comments carefully considered. Included in the guideline are epidemiology of allergic reactions to beta-lactams, molecular structure, formulations available in the UK and a description of known beta-lactam antigenic determinants. Sections on the value and limitations of clinical history, skin testing and laboratory investigations for both penicillins and cephalosporins are included. Cross-reactivity between penicillins and cephalosporins is discussed in detail. Recommendations on oral provocation and desensitization procedures have been made. Guidance for beta-lactam allergy in children is given in a separate section. An algorithm to help the clinician in the diagnosis of patients with a history of penicillin allergy has also been included.

Evaluating the Usefulness of Retesting for Beta-lactam Allergy in Children

Many children with adverse reactions to beta-lactams are labeled as allergic without performing an allergy study to confirm it. In this retrospective study of 10 years, we detected only 3.3% positive cases. Although international guidelines recommend a second allergy workup in patients with a negative study, we found from our results a low profitability of retesting.

Beta lactam allergy in children from two ethnically different populations

The effects of ethnicity on beta lactam allergy have not been reported. The Negev Desert in Southern Israel is inhabited by two ethnically distinct populations: Jews and Bedouin Muslims. Approximately 60% of the pediatric population of the area is Jewish. Whereas most Jews live in Westernized urban centers, Bedouins are in the process of transition from semi-nomadic conditions to a sedentary lifestyle and the majority of them now live in towns and villages. We sought to determine the rate and characteristics of physician-reported beta lactam allergy in Jewish and Bedouin children. The medical records of all children registered in five primary community clinics were reviewed and screened for allergy to beta lactam antibiotics. A total of 26,655 medical records were reviewed: of 11,069 Jewish children and 15,586 Bedouin children. Beta lactam allergy was registered in 344 records (1.3%), and was more frequent in Jewish (n= 226, 2.1%) than in Bedouin children (n= 118, 0.8%, P < 0.0001). Beta lactam allergy was more common in boys in both populations (P < 0.01). The clinical features of the reaction that led to the diagnosis of beta lactam allergy were not significantly different between the two ethnic populations, although the specific antibiotics prescribed and the diagnoses for which they were prescribed were different in the two ethnic populations. We concluded in this study that pediatric beta lactam allergy was registered more frequently in Jewish than in Bedouin children, and in boys more than in girls.

Authors reply to beta‐lactam allergy in children

Authors reply to beta‐lactam allergy in children

Beta‐lactam allergy in children

Beta‐lactam allergy in children