Phage-based assay to measure daptomycin concentration in biological fluids

 描述（由申请人提供）：严重革兰氏阳性菌感染难以治疗，并且在医院环境中死亡率较高。达托霉素是一种广谱抗生素，已成功用于治疗持续性革兰氏阳性菌感染，包括皮肤和软组织感染、右侧心内膜炎和菌血症。达托霉素对耐药菌株如耐甲氧西林沙门氏菌也非常有效。金黄色葡萄球菌（MRSA）和万古霉素耐药肠球菌（VRE）。目前的达托霉素给药指南来自健康个体的有限研究，其中药代动力学是高度可预测的。不幸的是，达托霉素的药代动力学在通常接受该药物的重症患者中变化很大。这导致亚治疗剂量，治疗失败率增加，以及近年来达托霉素耐药菌株的出现。因此，达托霉素浓度的治疗监测将使临床医生能够调整剂量，以保持有效的循环浓度，最终改善结果并预防不良反应。不幸的是，没有FDA批准的测试来测量临床环境中的达托霉素浓度。多项临床研究得出的结论是，目前危重病和脓毒症患者的达托霉素给药指南需要重新评估和调整，需要定期测量这些患者的达托霉素水平以确保有效治疗。为了满足这一关键需求，Affinergy正在开发一种新的检测方法，使用达托霉素结合噬菌体来测量血浆中的达托霉素浓度。在该II期项目结束时，我们将提交一份监管申报材料，以获得FDA对我们检测试剂盒的批准。

 DESCRIPTION (provided by applicant): Severe Gram-positive infections are difficult to treat and associated with high mortality in hospital settings. Daptomycin is a broad spectrum antibiotic that has been successfully used to treat persisting Gram-positive infections, including skin and soft tissue infections, right-sided endocarditis, and bacteremia. Daptomycin is also highly effective against drug-resistant strains such as methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci (VRE). Current daptomycin dosing guidelines are derived from limited studies in healthy individuals, where pharmacokinetics are highly predictable. Unfortunately, daptomycin pharmacokinetics are highly variable in the critically ill patients that typically receive the drug. This leads to sub-therapeutic dosing, increased rates of treatment failure, and in recent years, the emergence of daptomycin-resistant strains. Therapeutic monitoring of daptomycin concentrations would thus enable clinicians to adjust doses in order to maintain an effective circulating concentration, ultimately improving outcomes and preventing adverse effects. Unfortunately, there is no FDA-approved test to measure daptomycin concentrations in a clinical setting. Multiple clinical studies have concluded that current daptomycin dosing guidelines for critically ill and septic patients need to be reevaluated and adjusted, and regular measurement of daptomycin levels in these patients are needed to ensure effective treatment. To address this critical need, Affinergy is developing a novel assay format using daptomycin-binding phage to measure daptomycin concentrations in plasma. At the conclusion of this Phase II project, we will file a regulatory submission for FDA clearance of our assay.