Harvard Medical School, Boston, Massachusetts.
Division of Rheumatology. Allergy and Immunology, Department of Medicine, Massachusetts General Hospital, Boston.
JAMA Intern Med. 2024 Nov 1;184(11):1374-1383. doi: 10.1001/jamainternmed.2024.4606.
While direct penicillin challenges might support the expansion of penicillin allergy delabeling efforts, the perceived risk of reactions remains a key barrier.
To evaluate the frequency of reactions to direct penicillin challenges in individuals with penicillin allergy labels and to identify factors associated with such reactions.
Three electronic databases were searched (MEDLINE, Web of Science, and Scopus) from inception to July 19, 2023, for primary studies assessing patients undergoing direct penicillin challenges. Articles were included regardless of publication year, language, status, or definition of allergy risk.
Two reviewers independently selected original studies reporting the frequency of immunologically mediated reactions following a direct penicillin challenge in patients reporting a penicillin allergy.
Two reviewers independently extracted data and independently assessed the quality of each primary study using a risk-of-bias tool for prevalence studies.
The primary outcome was the frequency of reactions to direct penicillin challenges as calculated using random-effects bayesian meta-analysis of proportions. Secondary outcomes included risk factors for reactions and the frequency of severe reactions.
A total of 56 primary studies involving 9225 participants were included. Among participants, 438 experienced reactions to direct penicillin challenges without prior testing, corresponding to an overall meta-analytic frequency of 3.5% (95% credible interval [CrI], 2.5%-4.6%). Meta-regression analyses revealed that studies performed in North America had lower rates of reaction to direct challenges (odds ratio [OR], 0.36; 95% CrI, 0.20-0.61), while studies performed in children (OR, 3.37; 95% CrI, 1.98-5.98), in outpatients (OR, 2.19; 95% CrI, 1.08-4.75), and with a graded (OR, 3.24; 95% CrI, 1.50-7.06) or prolonged (OR, 5.45; 95% CrI, 2.38-13.28) challenge had higher rates of reaction. Only 5 severe reactions (3 anaphylaxis, 1 fever with rash, and 1 acute kidney injury) were reported, none of which were fatal.
This systematic review and meta-analysis found that reactions to direct penicillin challenges are infrequent, with rates comparable to indirect challenges after allergy testing. These findings suggest that direct challenges are safe for incorporation into penicillin allergy evaluation efforts across age groups and clinical settings.
虽然直接青霉素挑战可能支持扩大青霉素过敏标签去除工作，但人们对反应的担忧仍然是一个关键障碍。
评估有青霉素过敏标签的个体中直接青霉素挑战的反应频率，并确定与这些反应相关的因素。
从创建到 2023 年 7 月 19 日，三个电子数据库（MEDLINE、Web of Science 和 Scopus）都被搜索到，用于评估进行直接青霉素挑战的患者的主要研究。无论研究的出版年份、语言、状态或过敏风险定义如何，都包括了这些文章。
两名审查员独立选择了报告报告青霉素过敏的患者在直接青霉素挑战后发生免疫介导反应频率的原始研究。
两名审查员独立提取数据，并使用患病率研究的偏倚风险工具独立评估每项原始研究的质量。
主要结果是使用随机效应贝叶斯荟萃分析比例计算的直接青霉素挑战反应的频率。次要结果包括反应的危险因素和严重反应的频率。
共有 56 项涉及 9225 名参与者的主要研究被纳入。在参与者中，有 438 名在未经预先测试的情况下对直接青霉素挑战有反应，总体荟萃分析频率为 3.5%（95%可信区间[CrI]，2.5%-4.6%）。元回归分析显示，在北美进行的研究中，直接挑战的反应率较低（比值比[OR]，0.36；95% CrI，0.20-0.61），而在儿童（OR，3.37；95% CrI，1.98-5.98）、门诊患者（OR，2.19；95% CrI，1.08-4.75）和分级（OR，3.24；95% CrI，1.50-7.06）或延长（OR，5.45；95% CrI，2.38-13.28）挑战中，反应率更高。仅报告了 5 例严重反应（3 例过敏反应、1 例发热伴皮疹和 1 例急性肾损伤），均非致命。
本系统评价和荟萃分析发现，直接青霉素挑战的反应并不常见，其发生率与过敏测试后的间接挑战相当。这些发现表明，直接挑战在各个年龄段和临床环境中纳入青霉素过敏评估工作是安全的。
