A novel, non-antibiotic, microbiome-directed agent to prevent post-surgical infection

一种新型、非抗生素、微生物组导向剂，用于预防术后感染

• 批准号: 10600765
• 负责人: John C Alverdy
• 金额: $ 29.91万
• 依托单位: COVIRA SURGICAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10600765
• 关键词: Adverse event; Affect; American; Anastomosis - action; Animal Model; Animal Testing; Animals; Antibiotic Resistance; Antibiotics; Asepsis; Bacteria; Bacterial Antibiotic Resistance; Biological; Biopsy; Canis familiaris; Clinical; Clinical Research; Clinical Trials; Colorectal; Control Groups; Data; Deposition; Diagnostic tests; Dose; Endoscopy; Enterococcus faecalis; Epithelium; Equus caballus; Excision; Exposure to; Family suidae; Fascia; Gastrointestinal Surgical Procedures; Growth; Health Care Costs; Health Expenditures; Health Promotion; High Pressure Liquid Chromatography; Histologic; Hospitalization; Human; Image; Infection; Infection prevention; Inpatients; Intestinal Diseases; Intestines; Intravenous; Invaded; Ions; Life; MMP9 gene; Maximum Tolerated Dose; Measures; Methods; Microbe; Morbidity - disease rate; Mucins; Muscle; Operative Surgical Procedures; Oral; Oral Administration; Organ; Pathogenicity; Patients; Phase; Phenotype; Polyethylene Glycols; Polymers; Postoperative Period; Postoperative Wound Infection; Preclinical Testing; Process; Production; Proliferating; Prophylactic treatment; Protocols documentation; Pseudomonas aeruginosa; Radiation; Rattus; Recovery; Rodent; Safety; Sampling; Sepsis; Serum; Site; Skin; Small Business Technology Transfer Research; Source; Surface; Surgical Models; Surgical Wound Infection; Surgical incisions; Testing; Time; Tissue Sample; Tissues; Toxic effect; Virulence; Virulent; Work; Wound Infection; absorption; analytical method; chemotherapy; clinical development; clinical examination; clinically relevant; collagenase; comparison control; drinking water; emerging antimicrobial resistance; experimental group; first-in-human; gut microbiome; gut microbiota; high risk; human pathogen; improved; inorganic phosphate; large scale production; manufacture; microbiome; microbiota; migration; mortality; novel; pathogen; porcine model; pre-clinical; preclinical development; preclinical safety; preclinical study; prevent; programs; prophylactic; safety study; treatment duration; western diet; wound

SUMMARY Covira Surgical, Inc. is developing CS-0003, a first-in-class, orally administered non-antibiotic therapy for preventing infections in patients undergoing gastrointestinal (GI) surgeries. Despite improved surgical procedures, broad use of antibiotics, mandated asepsis measures, and enhanced recovery programs, post-surgical infections remain a clear and present danger to patients. Surgical site infections (SSIs) are a major cause of morbidity, prolonged hospitalization, increased healthcare expenditures, and mortality for the approximately four million Americans who undergo inpatient GI surgery annually. While SSIs can result from direct intraoperative contamination of the surgical site, emerging evidence suggests that many, if not most SSIs (wound infections, organ space infections, anastomotic leaks) may originate from the patient’s own microbiota. Common pathogens causing such complications (i.e., Enterococcus faecalis, Pseudomonas aeruginosa) may be present in the gut before surgery. It is estimated that 50% or more of the pathogens causing SSIs are now resistant to antibiotics chosen for prophylaxis. CS-0003 prevents SSI by maintaining the health-promoting effects of the native gut microbiota while suppressing the virulence of the proliferating pathobiota. CS-0003 directly suppresses bacterial virulence without affecting bacterial growth: it provides microbes with a readily available source of phosphate while providing a physical shield against bacteria from adhering to and invading the epithelial surface. CS-0003 is intended for use immediately before and after surgery. Rodent studies show that CS-0003 prevents SSI against multiple human pathogens and across various surgical models relevant to the human condition. The overall objective of this Fast-Track STTR is to advance the preclinical and clinical development of CS-0003 as an adjunctive measure to prevent SSIs. In Phase I, we will demonstrate CS-0003 efficacy in a large animal model. In Phase II, we will develop methods for large-scale CS-0003 production and then perform comprehensive preclinical testing. Successful completion of the project will provide the data required for IND submission.

总结 Covira Surgical，Inc.正在开发CS-0003，这是一种一流的口服非抗生素疗法 用于预防胃肠道（GI）手术患者感染。 尽管改进了外科手术，广泛使用抗生素，强制性无菌措施，并加强了 尽管有康复计划，但术后感染仍然是患者面临的明显危险。手术部位感染 （SSI）是发病、住院时间延长、医疗费用增加和 每年约有400万美国人接受住院胃肠道手术。 虽然SSI可能由手术部位的术中直接污染引起，但新的证据表明， 许多（如果不是大多数）SSI（伤口感染、器官间隙感染、吻合口漏）可能源于 患者自身的微生物群。引起这种并发症的常见病原体（即，粪肠球菌， 铜绿假单胞菌）可能存在于手术前的肠道中。据估计，50%或更多的 引起SSI的病原体现在对选择用于预防的抗生素具有抗性。 CS-0003通过维持天然肠道微生物群的健康促进作用，同时抑制 增殖的病原生物群的毒性。CS-0003直接抑制细菌毒力， 细菌生长：它为微生物提供了一个容易获得的磷酸盐来源，同时提供了一个物理 防止细菌粘附和侵入上皮表面。CS-0003预期用于 在手术前后。啮齿类动物研究表明，CS-0003可预防针对多种人类的SSI 病原体和与人体状况相关的各种手术模型。 本快速通道STTR的总体目标是推进以下药物的临床前和临床开发： CS-0003作为预防SSI的预防措施。在第一阶段，我们将证明CS-0003的疗效， 大型动物模型。在第二阶段，我们将开发大规模生产CS-0003的方法， 然后进行全面的临床前测试。该项目的成功完成将提供数据 需要提交IND。