Safety and tolerability of a single administration of AR-301, a human monoclonal antibody, in ICU patients with severe pneumonia caused by Staphylococcus aureus: first-in-human trial
Safety and tolerability of a single administration of AR-301, a human monoclonal antibody, in ICU patients with severe pneumonia caused by Staphylococcus aureus: first-in-human trial
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DOI：
10.1007/s00134-018-5229-2
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发表时间：
2018-11-01
影响因子：
38.9
通讯作者：
Laterre, Pierre-Francois
中科院分区：
文献类型：
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作者：
Francois, Bruno;Mercier, Emmanuelle;Laterre, Pierre-Francois
目的医院获得性细菌性肺炎（HABP）是医院中的一个严重问题，呼吸机相关性细菌性肺炎（VABP）仍然是ICU中最常见的感染，通常是由于金黄色葡萄球菌，一种越来越难以治疗的病原体。抗感染单克隆抗体（mAb）可能提供新的，有前途的治疗选择。这项随机、双盲、安慰剂对照研究旨在评估AR-301的安全性和药代动力学。金黄色葡萄球菌α毒素中和单克隆抗体，并探讨其临床和微生物学结果时，连续使用标准的护理抗生素。金黄色葡萄球菌肺炎，包括HABP、VABP或CABP，在ICU接受治疗，APACHE II评分30。在临床和微生物学确诊为沙门氏菌后，研究者选择的标准治疗抗生素被给予所有患者。金黄色肺炎开始AR-301的辅助治疗
PurposeHospital-acquired bacterial pneumonia (HABP) is a critical concern in hospitals with ventilator-associated bacterial pneumonia (VABP) remaining the most common infection in the ICU, often due to Staphylococcus aureus, an increasingly difficult to treat pathogen. Anti-infective monoclonal antibodies (mAb) may provide new, promising treatment options. This randomized, double-blinded, placebo-controlled study aimed at assessing the safety and pharmacokinetics of AR-301, an S. aureus alpha toxin-neutralizing mAb, and exploring its clinical and microbiologic outcomes when used adjunctively with standard-of-care antibiotics.MethodsEligibility in this trial required microbiologically confirmed severe S. aureus pneumonia, including HABP, VABP or CABP, treated in the ICU and an APACHE II score 30. Standard-of-care antibiotics selected by the investigators were administered to all patients in the study following clinical and microbiologic confirmation of S. aureus pneumonia. Adjunctive treatment of AR-301 was to start