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

基本信息

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
项目类别：
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

项目摘要

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.

概括 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接受胃肠道 (GI) 手术的患者感染。尽管改进了外科手术，广泛使用抗生素，强制采取无菌措施，并加强了恢复计划中，手术后感染仍然是手术部位感染的一个明显且现实的危险。 (SSIs) 是发病、住院时间延长、医疗保健支出增加和每年约有四百万美国人接受住院胃肠道手术的死亡率。虽然 SSI 可能是由手术部位的直接术中污染引起的，但新出现的证据表明许多（如果不是大多数）SSI（伤口感染、器官间隙感染、吻合口瘘）可能源自患者自身的微生物群引起此类并发症（即粪肠球菌，据估计，手术前肠道中可能存在铜绿假单胞菌 (Pseudomonas aeruginosa) 50% 或更多。引起 SSI 的病原体现在对用于预防的抗生素具有抗药性。 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 SSI CS-0003 可以直接抑制增殖性病原体的毒力，而不影响细菌的毒力。细菌生长：它为微生物提供容易获得的磷酸盐来源，同时提供物理 CS-0003 旨在防止细菌粘附和侵入上皮表面。啮齿类动物研究表明，CS-0003 可预防针对多种人类的 SSI。病原体以及与人类状况相关的各种手术模型。该快速通道 STTR 的总体目标是推进临床前和临床开发 CS-0003 作为预防 SSI 的辅助措施在第一阶段，我们将证明 CS-0003 的功效。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，项目的成功完成将提供数据。 IND 提交所需的。