Preventing Diabetic Foot Ulcers through Manipulating the Skin Microbiota

通过控制皮肤微生物群预防糖尿病足溃疡

• 批准号: 10409692
• 负责人: Mary-Claire Roghmann
• 金额: --
• 依托单位: BALTIMORE VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10409692
• 关键词: Acinetobacter baumannii; Adult; Amputation; Antibiotic Resistance; Antibiotics; Antimicrobial Resistance; Bacteria; Caring; Chlorhexidine; Chronic; Clinical; Clinical Trials; Data; Development; Diabetes Mellitus; Diabetic Foot; Diabetic Foot Ulcer; Diabetic Neuropathies; Double-Blind Method; Enterobacter cloacae; Enterococcus faecium; Foot Ulcer; Future; Gangrene; Genus staphylococcus; Goals; Heel; Hospitalization; Iatrogenesis; Immune response; Impaired wound healing; Incidence; Infection; Infectious Skin Diseases; Inflammation; Inflammatory Response; Intervention; Klebsiella pneumoniae; Local Anti-Infective Agents; Lower Extremity; Minor; Pathogenesis; Pathway interactions; Patients; Persons; Placebos; Prevalence; Prevention; Prevention Measures; Pseudomonas aeruginosa; Randomized; Recurrence; Risk; Role; Safety; Site; Skin; Staphylococcus aureus; Surgical Wound Infection; Testing; Trauma; Ulcer; Veterans; Veterans Health Administration; Work; chronic ulcer; clinically relevant; diabetic; disability; foot; healing; healthcare-associated infections; high risk; limb amputation; microbial; microbial colonization; microbiota; non-diabetic; pathogen; patient population; placebo group; prevent; skin disorder; skin microbiota; skin ulcer; topical antiseptic; wound healing

Diabetes is common in the Veterans Health Administration (VHA) patient population with a prevalence of 24% making it a priority clinical issue for Veterans. Between 10 and 25% of people with diabetes will develop a foot ulcer during their lifetime. Diabetic foot ulcers are a leading cause of hospitalization, as well as the primary cause of lower limb amputations. About 5% of patients with a foot ulcer require an amputation each year, typically due to the development of infection at the site of the foot ulcer. Because foot ulcers are a leading cause of disability in people with diabetes, more effective prevention is needed. The role of the skin microbiota on the development of chronic foot ulcers after minor trauma is unknown. Prior work has shown that the feet of diabetic Veterans had a higher load of S. aureus compared with non-diabetic veterans. Our preliminary data suggest that there are higher loads of S. aureus and total bacteria on the feet of diabetic Veterans at high risk for future foot ulcer compared to diabetic Veterans at low risk of a future foot ulcer. If so, manipulating the skin microbiota of the feet could reduce the risk of foot complications. Thus, we propose the following aims to test our central hypotheses that the skin microbiota is part of the causal pathway in the development of chronic ulcers. Using a randomized, double-blind clinical trial, 200 adults with diabetes and a prior foot ulcer will be randomly assigned to chlorhexidine or placebo wipes for daily foot care over one year. Specific Aim 1A: To determine if chlorhexidine reduces the recurrence of foot complications including chronic foot ulcer, foot infection or foot amputation. We hypothesize that the chlorhexidine group will have a lower incidence of chronic foot ulcer or foot infection or foot amputation than the placebo group. Specific Aim 1B: To determine if chlorhexidine increases antibiotic resistance among ESKAPE [and diabetic foot infection] pathogens. We hypothesize that a) the chlorhexidine group will not be colonized with E. cloacae, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa and E. faecium (ESKAPE) [and diabetic foot infection] pathogens with a higher MIC to chlorhexidine than the placebo group and b) the chlorhexidine group will not be colonized with ESKAPE [and diabetic foot infection] pathogens with a higher MIC to key antibiotics than the placebo group. We expect to gain: 1) an assessment of the feasibility of chlorhexidine as a daily intervention to prevent recurrent foot ulcers in Veterans with diabetes, and 2) an understanding of the risk of antimicrobial resistance with long term chlorhexidine use. Our long term goal is to test whether interventions which manipulate the skin microbiota prevent foot ulcers in a larger (adequately powered for a clinically relevant endpoint) clinical trial in order to reduce the risk of amputation associated with diabetic foot ulcers.

糖尿病在退伍军人健康管理局（VHA）患者人群中很常见，患病率为 24%，使其成为退伍军人的优先临床问题。10%到25%的糖尿病患者会出现 在一生中，足部溃疡。糖尿病足溃疡是住院治疗的主要原因，也是主要原因。 导致下肢截肢。每年约有5%的足部溃疡患者需要截肢， 通常是由于在足部溃疡部位发生感染。因为足部溃疡是 糖尿病患者的残疾原因，需要更有效的预防。皮肤微生物群的作用 对轻微创伤后慢性足部溃疡的发展尚不清楚。 先前的研究表明，糖尿病退伍军人的脚有较高的S。金黄色葡萄球菌与 非糖尿病退伍军人。我们的初步数据表明，有较高的负荷的S。金黄色葡萄球菌和细菌总数 糖尿病退伍军人的脚在高风险的未来足部溃疡相比，糖尿病退伍军人在低风险的足部溃疡， 未来的足部溃疡如果是这样的话，操纵足部的皮肤微生物群可以降低足部并发症的风险。 因此，我们提出以下目标来测试我们的中心假设，即皮肤微生物群是因果关系的一部分。 在慢性溃疡的发展途径。 采用随机、双盲临床试验，将对200名患有糖尿病和既往足部溃疡的成年人进行 随机分配洗必泰或安慰剂湿巾进行为期一年的日常足部护理。具体目标1A： 确定洗必泰是否可以减少足部并发症的复发，包括慢性足部溃疡，足部 感染或截肢。我们假设氯己定组的慢性炎症发生率较低， 足溃疡或足感染或足截肢率高于安慰剂组。具体目标1B：确定 洗必泰增加ESKAPE [和糖尿病足感染]病原体的抗生素耐药性。我们 假设a）洗必泰组不会被E. cloxacin，S.金黄色葡萄球菌K.肺炎杆菌A. 鲍曼不动杆菌、铜绿假单胞菌和E.屎肠菌（ESKAPE）[和糖尿病足感染]病原体具有较高的MIC， B）氯己定组不会被ESKAPE定殖[和 糖尿病足感染]病原体对关键抗生素的MIC高于安慰剂组。 我们期望获得：1）氯己定作为日常干预措施的可行性评估，以预防 患有糖尿病的退伍军人的复发性足部溃疡，以及2）了解抗菌素耐药性的风险 长期使用氯己定。我们的长期目标是测试是否干预，操纵皮肤 微生物群预防足部溃疡在一个更大的（充分把握度的临床相关终点）临床试验， 以降低与糖尿病足溃疡相关的截肢风险。