Division of Clinical Immunology and Allergy, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Institute of Health Policy, Management and Evaluation, Eliot Phillipson Clinician-Scientist Training Program, University of Toronto, Toronto, Ontario, Canada.
JAMA Dermatol. 2023 Apr 1;159(4):384-392. doi: 10.1001/jamadermatol.2022.6378.
Antibiotics are an important risk for Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), which are the most severe types of drug hypersensitivity reaction with a mortality rate up to 50%. To our knowledge, no global systematic review has described antibiotic-associated SJS/TEN.
To evaluate the prevalence of antibiotics associated with SJS/TEN worldwide.
The MEDLINE and Embase databases were searched for experimental and observational studies that described SJS/TEN risks since database inception to February 22, 2022.
Included studies adequately described SJS/TEN origins and specified the antibiotics associated with SJS/TEN.
Two reviewers (E.Y.L. and C.K.) independently selected the studies, extracted the data, and assessed the risk of bias. A meta-analysis using a random-effects model was performed in the studies that described patient-level associations. Subgroup analyses were performed to explore the heterogeneity. The risk of bias was assessed using the Joanna Briggs Institute checklist, and the certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
Prevalence of antibiotic-associated SJS/TEN was presented as pooled proportions with 95% CIs.
Among the 64 studies included in the systematic review, there were 38 studies that described patient-level associations; the meta-analysis included these 38 studies with 2917 patients to determine the prevalence of single antibiotics associated with SJS/TEN. The pooled proportion of antibiotics associated with SJS/TEN was 28% (95% CI, 24%-33%), with moderate certainty of evidence. Among antibiotic-associated SJS/TEN, the sulfonamide class was associated with 32% (95% CI, 22%-44%) of cases, followed by penicillins (22%; 95% CI, 17%-28%), cephalosporins (11%; 95% CI, 6%-17%), fluoroquinolones (4%; 95% CI, 1%-7%), and macrolides (2%; 95% CI, 1%-5%). There was a statistically significant heterogeneity in the meta-analysis, which could be partially explained in the subgroup analysis by continents. The overall risk of bias was low using the Joanna Briggs Institute checklist for case series.
In this systematic review and meta-analysis of all case series, antibiotics were associated with more than one-quarter of SJS/TEN cases described worldwide, and sulfonamide antibiotics remained the most important association. These findings highlight the importance of antibiotic stewardship, clinician education and awareness, and weighing the risk-benefit assessment of antibiotic choice and duration.
抗生素是史蒂文斯-约翰逊综合征和中毒性表皮坏死松解症（SJS/TEN）的一个重要风险因素，这是药物过敏反应中最严重的两种类型，死亡率高达 50%。据我们所知，尚无全球系统评价描述过抗生素相关性 SJS/TEN。
评估全球范围内与 SJS/TEN 相关的抗生素的流行情况。
从数据库建立到 2022 年 2 月 22 日，在 MEDLINE 和 Embase 数据库中检索描述 SJS/TEN 风险的实验和观察性研究。
纳入的研究充分描述了 SJS/TEN 的起源，并指定了与 SJS/TEN 相关的抗生素。
两名审查员（E.Y.L. 和 C.K.）独立选择研究、提取数据并评估偏倚风险。在描述患者水平关联的研究中进行了使用随机效应模型的荟萃分析。进行了亚组分析以探索异质性。使用 Joanna Briggs 研究所清单评估偏倚风险，并使用 GRADE（推荐评估、制定和评估）方法对证据的确定性进行评级。
抗生素相关性 SJS/TEN 的患病率以 95%CI 表示的汇总比例呈现。
在系统评价中纳入的 64 项研究中，有 38 项研究描述了患者水平的关联；荟萃分析纳入了这 38 项研究，其中有 2917 名患者，以确定与 SJS/TEN 相关的单一抗生素的患病率。抗生素相关性 SJS/TEN 的汇总比例为 28%（95%CI，24%-33%），证据确定性为中等。在抗生素相关性 SJS/TEN 中，磺胺类药物与 32%（95%CI，22%-44%）的病例相关，其次是青霉素类（22%；95%CI，17%-28%）、头孢菌素类（11%；95%CI，6%-17%）、氟喹诺酮类（4%；95%CI，1%-7%）和大环内酯类（2%；95%CI，1%-5%）。荟萃分析存在统计学显著的异质性，在按大陆进行的亚组分析中部分可以解释。使用病例系列 Joanna Briggs 研究所清单，总体偏倚风险较低。
在这项对所有病例系列的系统评价和荟萃分析中，抗生素与全球范围内描述的 SJS/TEN 病例的四分之一以上有关，磺胺类抗生素仍然是最重要的关联。这些发现强调了抗生素管理、临床医生教育和意识以及权衡抗生素选择和持续时间的风险-效益评估的重要性。
