Phage-based assay to measure daptomycin concentration in biological fluids

 描述（由申请方提供）：严重革兰氏阳性菌感染难以治疗，并且与医院环境中的高死亡率相关。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、增加的治疗失败率以及最近达托霉素抗性菌株的出现。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已经开始开发一种测定循环达托霉素浓度的方法。我们已经确定了一系列的噬菌体，结合与高亲和力和特异性达托霉素，我们正在开发一种ELISA型测定使用噬菌体作为一种高灵敏度的检测试剂。在第一阶段结束时，我们希望有一种技术，可以在第二阶段扩大规模，供临床医生和研究人员使用，以测量生物液体中的达托霉素浓度。

 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 is 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 recently, 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 has begun development of an assay to measure circulating daptomycin concentrations. We have identified a series of phage that bind with high affinity and specificity to daptomycin, and we are developing an ELISA-type assay using phage as a highly sensitive detection reagent. At the conclusion of Phase 1, we expect to have a technology that can be scaled up in Phase 2 for use by clinicians and researchers to measure daptomycin concentrations in biological fluids.