BETA-LACTAM ANTIBIOTIC ALLERGY

IgE抗体介导的对β-内酰胺类抗生素的反应 (青霉素类、头孢菌素类、碳青霉烯类和单巴菌素类) 经常使这些药物的治疗复杂化，并强制 严重限制了它们的使用。皮肤试验和体外特异性IgE 能够准确识别青霉素过敏患者的检测方法 已经被开发出来，但与以下几个重要问题有关 青霉素过敏仍未解决。结构相似的 β-内酰胺类抗生素，现在使用范围比 青霉素G，给诊断和治疗带来了新的问题 过敏反应的管理。中描述的实验 该提案涉及以下三个相关领域的基本问题 人β-内酰胺类药物过敏的诊断与处理 青霉素过敏；青霉素的体外检测和鉴定 对头孢菌素类药物的免疫球蛋白和头孢菌素的破坏过程 用β-内酰胺类抗生素决定因素替代的蛋白质。在……里面 第一组实验，新的体外检测方法 青霉素和常规青霉素皮试的结果将是 用于澄清与准确性有关的有争议的问题 青霉素过敏的诊断。相互矛盾的可能解释 对于急性β-内酰胺类药物，将进行脱敏研究。 β-内酰胺类药物Will治疗患者的复敏作用 被探索。第二组实验将研究IgE以 头孢菌素决定因素和由其他 β-内酰胺类药物使用新的体外检测方法。 头孢菌素与其他β-内酰胺类药物的交叉反应性 决定因素将被测量。第三组实验 将表征人类蛋白质的脱氢作用。近期 研究表明，人类血浆和血清有能力 去除共价结合在人硒上的青霉素决定簇 氨基和二硫键形成的白蛋白。这些活动将 特征及其与临床反应的关系 将对青霉素进行评估。这些相互关联的研究将提供 新的一般方法和对 β-内酰胺的免疫化学、诊断和脱敏 药物过敏。

IgE antibody mediated reactions to beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, and monobactams) frequently complicate therapy with these agents and impose a serious limitation on their use. Skin tests and in vitro specific IgE assays that can accurately identify penicillin allergic patients have been developed, but several important issues pertaining to penicillin allergy remain unresolved. The structurally similar beta-lactam antibiotics, now more widely used than benzylpenicillin G, impose new problems for diagnosis and management of allergic reactions. The experiments described in this proposal address fundamental issues in three related areas of human beta-lactam drug allergy: the diagnosis and management of penicillin allergy; the in vitro detection and characterization of IgE to cephalosporins; and the process of dehaptentation of proteins substituted with beta-lactam antibiotic determinants. In first group of experiments, new in vitro methods for the detection of IgE t penicillin and conventional penicillin skin tests will be used to clarify controversial issues pertaining to the accurate diagnosis of penicillin allergy. Competing possible explanations for acute beta-lactam drug desensitization will be investigated. Resensitization of patients treated with a beta-lactam drug will be explored. The second group of experiments will study IgE to cephalosporin determinants and determinants formed from other beta-lactam drugs using new in vitro assay methods. Crossreactivities among cephalosporin and other beta-lactam determinants will be measured. The third group of experiments will characterize dehaptenation of human proteins. Recent studies have disclosed the ability of human plasma and serum to remove penicillin determinants covalently attached to human se- albumin by amide and disulfide bonds. These activities will characterized and their relationship to clinical reactions to penicillin will be assessed. These interrelated studies will provide new general approaches and significant new insights into the immunochemistry, diagnosis, and desensitization of beta-lactam drug allergy.