Konvinse Katherine C, Phillips Elizabeth J, White Katie D, Trubiano Jason A
aDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA bInstitute for Immunology and Infectious Diseases, Murdoch University, Western Australia, Australia cDepartment of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA dDepartment of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, USA eDepartment of Infectious Diseases, Austin Hospital, Victoria, Australia fDepartment of Infectious Diseases, Alfred Hospital, Victoria, Australia gDepartment of Infectious Diseases, Peter MacCallum Cancer Centre, Victoria, Australia hDepartment of Medicine, University of Melbourne, Victoria, Australia.
Curr Opin Infect Dis. 2016 Dec;29(6):561-576. doi: 10.1097/QCO.0000000000000323.
Antimicrobials are a leading cause of severe T cell-mediated adverse drug reactions (ADRs). The purpose of this review is to address the current understanding of antimicrobial cross-reactivity and the ready availability of and evidence for in-vitro, in-vivo, and ex-vivo diagnostics for T cell-mediated ADRs.
Recent literature has evaluated the efficacy of traditional antibiotic allergy management, including patch testing, skin prick testing, intradermal testing, and oral challenge. Although patch and intradermal testing are specific for the diagnosis of immune-mediated ADRs, they suffer from drug-specific limitations in sensitivity. The use of ex-vivo diagnostics, especially enzyme-linked immunospot, has been highlighted as a promising new approach to assigning causality. Knowledge of true rates of antimicrobial cross-reactivity aids empirical antibiotic choice in the setting of previous immune-mediated ADRs.
In an era of increasing antimicrobial resistance and use of broad-spectrum antimicrobial therapy, ensuring patients are assigned the correct 'allergy label' is essential. Re-exposure to implicated antimicrobials, especially in the setting of severe adverse cutaneous reaction, is associated with significant morbidity and mortality. The process through which an antibiotic label gets assigned, acted on and maintained is still imprecise. Predicting T cell-mediated ADRs via personalized approaches, including human leukocyte antigen-typing, may pave future pathways to safer antimicrobial prescribing guidelines.
抗菌药物是严重T细胞介导的药物不良反应(ADR)的主要原因。本综述的目的是阐述目前对抗菌药物交叉反应性的理解,以及T细胞介导的ADR的体外、体内和离体诊断方法的可得性及证据。
近期文献评估了传统抗生素过敏管理方法的疗效,包括斑贴试验、皮肤点刺试验、皮内试验和口服激发试验。虽然斑贴试验和皮内试验对免疫介导的ADR诊断具有特异性,但它们在敏感性方面存在药物特异性限制。离体诊断方法的应用,尤其是酶联免疫斑点技术,已被视为一种有前景的因果关系判定新方法。了解抗菌药物交叉反应的真实发生率有助于在既往有免疫介导的ADR情况下进行经验性抗生素选择。
在抗菌药物耐药性增加和广泛使用广谱抗菌治疗的时代,确保为患者正确贴上“过敏标签”至关重要。再次接触相关抗菌药物,尤其是在严重皮肤不良反应的情况下,会导致显著的发病率和死亡率。抗生素标签的确定、执行和维持过程仍不精确。通过包括人类白细胞抗原分型在内的个性化方法预测T细胞介导的ADR,可能为制定更安全的抗菌药物处方指南开辟未来道路。