Phage-based assay to measure daptomycin concentration in biological fluids

 描述(由申请人提供)：严重的革兰氏阳性感染在医院环境中很难治疗，并与高死亡率有关。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。达托霉素对耐甲氧西林金黄色葡萄球菌(MRSA)和耐万古霉素肠球菌(VRE)等耐药菌株也非常有效。目前的达托霉素剂量指南来自健康个体的有限研究，在这些研究中，药代动力学是高度可预测的。不幸的是，在通常接受达托霉素治疗的危重患者中，达托霉素的药代动力学变化很大。这导致了亚治疗剂量、治疗失败率的增加，以及近年来出现了达托霉素耐药菌株。因此，对达托霉素浓度的治疗性监测将使临床医生能够调整剂量，以维持有效的循环浓度，最终改善结果并防止不良反应。不幸的是，目前还没有FDA批准的在临床环境中测量达托霉素浓度的试验。多项临床研究得出结论，目前用于危重和败血症患者的达托霉素剂量指南需要重新评估和调整，并需要定期测量这些患者的达托霉素水平，以确保有效的治疗。为了满足这一关键需求，AffinEnergy正在开发一种新的检测格式，使用达托霉素结合噬菌体来测量达托霉素在血浆中的浓度。在这个第二阶段项目结束时，我们将提交一份监管文件，要求FDA批准我们的检测。

 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.