注射用苄星青霉素皮试及再次皮试问题的系统评价

Systematic review on the necessity of skin testing and retesting for benzathine benzylpenillin for injection

目的为临床处置苄星青霉素皮试及再次皮试问题提供证据支持,提高诊疗效率,保证患者用药安全。方法从国家药品监督管理局官网、FDA官网,检索苄星青霉素说明书。检索PubMed、Embase、the Cochrane Library英文数据库,中国知网、万方数据知识服务平台、SinoMed中文数据库,筛选β内酰胺抗生素、青霉素及苄星青霉素皮试相关指南/共识/指导原则、苄星青霉素药代动力学及皮试的临床研究文献。结果检索获得苄星青霉素的中国药品说明书和FDA说明书;《β-内酰胺类抗菌药物皮肤试验指导原则(2021)》《青霉素皮肤试验临床操作专家共识(2022)》《中华人民共和国药典临床用药须知(2020版)》。纳入苄星青霉素相关药代动力学文献等文献12篇。中国药品说明书要求首次使用前要做皮试,FDA说明书未要求做皮试,但国内外说明书都强调要做好严重过敏反应救治准备。苄星青霉素药代动力学文献显示:苄星青霉素单次注射后第4周体内仍有药物浓度。结论本研究通过系统评价,对中国首次使用苄星青霉素需进行皮试的规定予以确认,并基于药代动力学证据,显示4周内重复皮试可能没有必要。建议多学科专家基于证据对苄星青霉素再次皮试的问题通过共识,形成清晰的指导意见,以利于一线医务工作者规范执行。但无论是否进行皮试或再次皮试,应做好严重过敏反应救治准备。

Objective To provide evidence-based support for the clinical management of skin testing and retesting for benzathine benzylpenicillin,improving diagnostic and treatment efficiency while ensuring patient medication safety.Methods Instructions for benzathine benzylpenicllin were retrieved from the official websites of the China National Medical Products Administration(NMPA)and the FDA.PubMed,Embase,the Cochrane Library,CNKI,Wanfang data,and SinoMed databas-es were searched for guidelines/consensus/guidance onβ-lactam antibiotics,penicillin,and benzathine benzylpenicillin skin testing,as well as pharmacokinetic and clinical research literature on benzathine benzylpenicillin and its skin tests.Results The benzathine benzylpenicillin package inserts from the NMPA and FDA were obtained,along with the"Guidelines for Skin Testing ofβ-lactam Antibiotics(2021)","Expert Consensus on Clinical Operation of Penicillin Skin Test(2022)"and"lnstruc-tions for Clinical Use of the Pharmacopoeia of the People's Republic of China(2020 Edition)".Twelve articles related to the pharmacokinetics of benzathine benzylpenicillin and other relevant topics were included.The Chinese drug information sheet requires a skin test before the initial use of benzathine benzylpenicillin,whereas the FDA sheet does not mandate it.However,both emphasize the preparedness for managing severe allergic reactions.Pharmacokinetic studies revealed that benzathine ben-zylpenicillin concentrations remain in the body up to the fourth week post-injection.Conclusion This study through a systematic review,confirms the Chinese stipulation requiring a skin test prior to the initial administration of benzathine benzylpenicillin.Drawing upon pharmacokinetic evidence,it suggests that retesting within four weeks may not be necessary.It is recommended that multidisciplinary experts reach a consensus,grounded in evidence,to formulate clear guidelines for the retesting of benzathine benzylpenicilin,thereby facilitating standardized implementation by frontline healthcare practitioners.Nevertheless,the paramount importance lies in being fully prepared for managing severe allergic reactions,regardless of whether a skin test orretest is conducted.