The Combined Utility of Ex Vivo IFN-γ Release Enzyme-Linked ImmunoSpot Assay and In Vivo Skin Testing in Patients with Antibiotic-Associated Severe Cutaneous Adverse Reactions.
The Combined Utility of Ex Vivo IFN-γ Release Enzyme-Linked ImmunoSpot Assay and In Vivo Skin Testing in Patients with Antibiotic-Associated Severe Cutaneous Adverse Reactions.
复制标题
DOI：
10.1016/j.jaip.2017.09.004
复制
发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Phillips EJ
中科院分区：
文献类型：
--
作者：
Trubiano JA;Strautins K;Redwood AJ;Pavlos R;Konvinse KC;Aung AK;Slavin MA;Thursky KA;Grayson ML;Phillips EJ
对于同时使用多种抗生素相关的严重皮肤不良反应（scar），临床因果关系具有挑战性，诊断方法有限，导致未来抗生素选择受限。在一组抗生素相关(AA)- scar患者中，研究体内和体外诊断方法在确定药物因果关系方面的联合应用。2015年4月至2017年2月期间前瞻性招募aa - scar患者。体内试验（贴片试验或延迟皮内试验）在最高无刺激性浓度下对涉及的抗生素进行，并在24小时至1周内读取。体外试验使用一系列药理学相关浓度的相关抗生素刺激患者外周血单个核细胞（PBMCs），通过酶联免疫斑点法测量CD4D和CD8D T细胞中IFN-g释放的剂量依赖性。在19例aa - scar患者中，15例（79%）患者的体内和体外联合测试确定了抗生素的因果关系。10例（53%）aa -SCAR患者IFN-g释放酶联免疫斑点试验呈阳性，总体报告敏感性为52% (95% CI, 29-76)，特异性为100% (95% CI, 79-100)，在急性（SCAR发病后1天至6周内）检测（75%）和表型评分较高的患者（59%）中，敏感性有所提高。在体外或体内检测结果呈阳性的患者中进行检测后，相关类的窄谱β -内酰胺类和抗生素的使用增加。我们展示了在aa - scar患者体内和体外联合检测的潜在效用，以高特异性地确定药物因果关系。
For severe cutaneous adverse reactions (SCARs) associated with multiple antibiotics dosed concurrently, clinical causality is challenging and diagnostic approaches are limited, leading to constricted future antibiotic choices. To examine the combined utility of in vivo and ex vivo diagnostic approaches at assigning drug causality in a cohort of patients with antibiotic-associated (AA)-SCARs. Patients with AA-SCARs were prospectively recruited between April 2015 and February 2017. In vivo testing (patch testing or delayed intradermal testing) was performed to the implicated antibiotic(s) at the highest nonirritating concentration and read at 24 hours through 1 week. Ex vivo testing used patient peripheral blood mononuclear cells (PBMCs) stimulated with a range of pharmacologically relevant concentrations of implicated antibiotics to measure dose-dependent IFN-g release from CD4D and CD8D T cells via an enzyme-linked immunoSpot assay. In 19 patients with AA-SCARs, combined in vivo and ex vivo testing assigned antibiotic causality in 15 (79%) patients. Ten patients (53%) with AA-SCARs were positive on IFN-g release enzyme-linked immunoSpot assay, with an overall reported sensitivity of 52% (95% CI, 29-76) and specificity of100% (95% CI, 79-100), with improved sensitivity noted in acute (within 1 day to 6 weeks after SCAR onset) testing (75%) and in patients with higher phenotypic scores (59%). There was increased use of narrow-spectrum beta-lactams and antibiotics from within the implicated class following testing in patients with a positive ex vivo or in vivo test result. We demonstrate the potential utility of combined in vivo and ex vivo testing in patients with AA-SCARs to assign drug causality with high specificity.
登录
查看更多内容
影响因子：
3.8
作者：
Phillips, EJ;Sullivan, JR;Shear, NH
通讯作者：
Shear, NH
影响因子：
3.7
作者：
Huo ZY;Peng L
通讯作者：
Peng L
影响因子：
4
作者：
Keane, Niamh M.;Roberts, Steven G.;John, Mina
通讯作者：
John, Mina
影响因子：
6.7
作者：
NARANJO, CA;BUSTO, U;GREENBLATT, DJ
通讯作者：
GREENBLATT, DJ
影响因子：
30.5
作者：
Grimbaldeston, Michele A.;Nakae, Susumu;Galli, Stephen J.
通讯作者：
Galli, Stephen J.