Microbiologic impact of medical therapies for recurrent Clostridium difficile infection

药物治疗对复发性艰难梭菌感染的微生物学影响

• 批准号: 10427235
• 负责人: Curtis Donskey
• 金额: --
• 依托单位: LOUIS STOKES CLEVELAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10427235
• 关键词: Address; Aftercare; Antibiotic Therapy; Bacteria; Bacteroides; Bifidobacterium; Clinical; Clostridium difficile; Collaborations; Colon; Communities; Complication; Data; Dose; Drug Exposure; Feces; Healthcare Systems; Hospital Nursing; Indigenous; Infection; Intestines; Laboratories; Length of Stay; Medical; Microbiology; Morbidity - disease rate; Nursing Homes; Participant; Patients; Physiologic pulse; Principal Investigator; Quality of life; Recovery; Recurrence; Regimen; Reproduction spores; Research; Research Personnel; Risk; Testing; Treatment Protocols; Vancomycin; colonization resistance; cooperative study; cost; effective therapy; experience; gut microbiota; microbiota; mortality; mouse model; programs; randomized trial; recurrent infection; standard care; stool sample; success; transmission process; treatment duration; treatment group; trial comparing

Approximately 25% of patients responding to treatment for initial cases of Clostridium difficile infection (CDI) develop a recurrence of the infection, and many develop multiple recurrences. Unfortunately, the optimal medical management of recurrent CDI is unclear. In particular, vancomycin taper and pulse regimens are commonly used, but have not been compared to other medical treatments in randomized trials. To address this deficiency, the VA Cooperative Studies Program (CSP) is conducting a randomized trial, CSP596, to compare a standard 10-day course of vancomycin versus 10 days of fidaxomicin versus 10 days of vancomycin followed by a vancomycin taper and pulse regimen for first or second recurrences of CDI. We propose to conduct a sub-study of the CSP trial to develop a better understanding of the microbiologic impact of the treatment regimens. The central hypothesis of the proposal is that taper and pulse treatment regimens facilitate clearance of spores from the colon while allowing recovery of intestinal microbiota that provide colonization resistance to C. difficile. Our first specific aim is to compare the composition of the indigenous intestinal microbiota and clearance of C. difficile in patients receiving treatment with vancomycin taper and pulse regimens versus standard vancomycin or fidaxomicin regimens for recurrent CDI. To accomplish this aim, we will collect stool specimens before, during, and after treatment for a subset of 120 participants in the VA CSP trial (~40 per treatment group). We will compare the composition of the microbiota and the presence and concentration of C. difficile in stool of patients in each treatment group. Our second specific aim is to determine if pulse dosing of vancomycin and fidaxomicin enhances clearance of C. difficile spores. To accomplish this aim, we will use a mouse model of C. difficile colonization to compare clearance of C. difficile spores and recovery of the microbiota with every 2 or 3-day pulse dosing of vancomycin or fidaxomicin in comparison to daily dosing for the same treatment duration and to the standard 10-day treatment regimens used in the CSP# 596 trial. The results will be significant because recurrent CDI is an important clinical challenge and there is an urgent need for effective management approaches.

大约25％的艰难梭状芽胞杆菌治疗的患者中有25％ 感染（CDI）发生了感染的复发，许多人出现了多种复发。 不幸的是，尚不清楚复发性CDI的最佳医疗管理。尤其， 万古霉素锥度和脉搏方案通常使用，但尚未与其他 随机试验中的医疗治疗。为了解决这一缺陷，VA合作研究 程序（CSP）正在进行一项随机试验CSP596，以比较标准的10天课程 万古霉素与10天的fidaxomicin与10天的万古霉素，然后是 CDI的第一或第二复发的万古霉素锥度和脉搏方案。我们建议 进行CSP试验的子研究，以更好地了解微生物学的影响 治疗方案。该提案的中心假设是锥度和脉搏 治疗方案有助于清除结肠的孢子，同时恢复 肠道菌群可为艰难梭菌提供定殖的抗性。我们的第一个具体目的是 比较土著肠道菌群的组成和艰难梭菌中的清除 接受万古霉素锥度治疗的患者与标准治疗 复发性CDI的万古霉素或由联糖素方案。为了实现这一目标，我们将收集 粪便在VA CSP中的120名参与者的子集之前，期间和治疗后的标本 试验（每个治疗组约40）。我们将比较菌群的组成和 每个治疗组患者粪便中艰难梭菌的存在和浓度。我们的第二个 具体目的是确定万古霉素和虚拟蛋白的脉搏剂量是否增强清除率 艰难梭菌的孢子。为了实现这一目标，我们将使用艰难梭菌定植的小鼠模型 比较艰难梭菌孢子的间隙和每2或3天的菌群回收率 与每日剂量相比，脉搏给万古霉素或虚拟蛋白的脉搏剂量 CSP＃596试验中使用的持续时间和标准的10天治疗方案。结果 会很大 需要有效的管理方法。