加拿大多伦多大学David N. Juurlink团队研究了口服抗生素与严重皮肤药物不良反应风险之间的相关性。相关论文于2024年8月8日发表在《美国医学会杂志》上。

严重的皮肤药物不良反应（cADR）是涉及皮肤和内脏器官的潜在危及生命的药物超敏反应。抗生素是这些反应的公认原因，但尚无研究比较过不同抗生素类别的相对风险。

为了探讨与常用口服抗生素相关的严重cADR的风险，并描述为此住院的患者的预后，研究组进行了一项巢式病例对照研究，使用基于人群的关联管理数据集，对2002年至2022年间在加拿大安大略省接受过至少一种口服抗生素的66岁或以上成年人进行研究。病例是指在处方后60天内因严重cADR而就诊或住院的患者，每个病例都与多达4名未就诊的对照组相匹配。暴露因素为各类口服抗生素。以大环内酯类为参照组，对不同类别的口服抗生素与严重cADR之间的关联进行条件逻辑回归估计。

在20年的研究期间，研究组确定了21758名老年人（中位年龄为75岁；64.1%为女性）在抗生素治疗后因严重cADR而进行急诊就诊或住院，87025名匹配的对照组没有严重cADR。在初步分析中，与大环内酯类相比，磺胺类抗生素（调整后的比值比[aOR]，2.9；95%置信区间，2.7-3.1）和头孢菌素类（aOR，2.6；95%置信范围，2.5-2.8）与严重cADR的相关性最强。而呋喃妥因（aOR，2.2；95%CI，2.1-2.4）、青霉素类（aOR：1.4；95%CI：1.3-1.5）和氟喹诺酮类（aOR:1.3；95%CI；1.2-1.4）有明显的相关性。头孢菌素类抗生素（每1000张处方4.92次；95%CI，4.86-4.99）和磺胺类抗生素（每1000张处方3.22次；95%CI，3.15-3.28）的急诊就诊或因cADR住院的粗发生率最高。在2852例因cADR住院的患者中，中位住院时间为6天（IQR，3-13天），9.6%需要转至重症监护室，5.3%在医院死亡。

研究结果表明，与大环内酯类相比，常用的口服抗生素与严重cADR的风险增加有关，磺胺类和头孢菌素类风险最高。处方医生应在临床上适当的情况下优先使用低风险抗生素。

附：英文原文

Title: Oral Antibiotics and Risk of Serious Cutaneous Adverse Drug Reactions

Author: Erika Y. Lee, Tara Gomes, Aaron M. Drucker, Nick Daneman, Ayesha Asaf, Fangyun Wu, Vincent Piguet, David N. Juurlink

Issue&Volume: 2024-08-08

Abstract:

Importance  Serious cutaneous adverse drug reactions (cADRs) are potentially life-threatening drug hypersensitivity reactions involving the skin and internal organs. Antibiotics are a recognized cause of these reactions, but no studies have compared relative risks across antibiotic classes.

Objectives  To explore the risk of serious cADRs associated with commonly prescribed oral antibiotics, and to characterize outcomes of patients hospitalized for them.

Design, Setting, and Participants  Nested case-control study using population-based linked administrative datasets among adults aged 66 years or older who received at least 1 oral antibiotic between 2002 and 2022 in Ontario, Canada. Cases were those who had an emergency department (ED) visit or hospitalization for serious cADRs within 60 days of the prescription, and each case was matched with up to 4 controls who did not.

Exposure  Various classes of oral antibiotics.

Main Outcomes and Measures  Conditional logistic regression estimate of the association between different classes of oral antibiotics and serious cADRs, using macrolides as the reference group.

Results  During the 20-year study period, we identified 21758 older adults (median age, 75 years; 64.1% female) who had an ED visit or hospitalization for serious cADRs following antibiotic therapy and 87025 matched controls who did not. In the primary analysis, sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9; 95% CI, 2.7-3.1) and cephalosporins (aOR, 2.6; 95% CI, 2.5-2.8) were most strongly associated with serious cADRs relative to macrolides. Additional associations were evident with nitrofurantoin (aOR, 2.2; 95% CI, 2.1-2.4), penicillins (aOR, 1.4; 95% CI, 1.3-1.5), and fluoroquinolones (aOR, 1.3; 95% CI, 1.2-1.4). The crude rate of ED visits or hospitalization for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions; 95% CI, 4.86-4.99) and sulfonamide antibiotics (3.22 per 1000 prescriptions; 95% CI, 3.15-3.28). Among the 2852 case patients hospitalized for cADRs, the median length of stay was 6 days (IQR, 3-13 days), 9.6% required transfer to a critical care unit, and 5.3% died in the hospital.

Conclusion and Relevance  Commonly prescribed oral antibiotics are associated with an increased risk of serious cADRs compared with macrolides, with sulfonamides and cephalosporins carrying the highest risk. Prescribers should preferentially use lower-risk antibiotics when clinically appropriate.

DOI: 10.1001/jama.2024.11437

Source: https://jamanetwork.com/journals/jama/fullarticle/2822097