Preventing Diabetic Foot Ulcers through Manipulating the Skin Microbiota

糖尿病在退伍军人健康管理局(VHA)患者中很常见，患病率为 24%的人认为这是退伍军人的优先临床问题。10%至25%的糖尿病患者将发展为 他们一生中都会出现脚部溃疡。糖尿病足溃疡是住院的主要原因，也是主要的 导致截肢的原因。每年约有5%的足部溃疡患者需要截肢， 通常是由于足部溃疡部位的感染所致。因为足部溃疡是最主要的 对于糖尿病患者的致残原因，需要更有效的预防措施。皮肤微生物区系的作用 关于轻微创伤后慢性足部溃疡的发展情况尚不清楚。 先前的研究表明，与患糖尿病的退伍军人相比，患糖尿病的退伍军人的脚上有更多的金黄色葡萄球菌 非糖尿病退伍军人。我们的初步数据表明，金黄色葡萄球菌和细菌总数的载量较高。 糖尿病退伍军人与糖尿病退伍军人相比，糖尿病退伍军人未来足部溃疡的风险较高 未来的脚部溃疡。如果是这样的话，操纵足部皮肤微生物区系可以降低足部并发症的风险。 因此，我们提出以下目的来验证我们的中心假设，即皮肤微生物区系是原因的一部分 在慢性溃疡的发展过程中的途径。 使用随机、双盲临床试验，200名患有糖尿病和既往足部溃疡的成年人将被 随机分配给洗必泰或安慰剂湿巾进行一年多的日常足部护理。具体目标1A： 确定洗必泰是否可减少足部并发症的复发，包括慢性足部溃疡、足部 感染或足部截肢。我们假设洗必泰治疗组将会有较低的慢性 足部溃疡或足部感染或足部截肢优于安慰剂组。具体目标1B：确定 洗必泰增加了ESKAPE[和糖尿病足感染]病原体对抗生素的耐药性。我们 假设a)洗必泰不会被阴沟肠杆菌、金黄色葡萄球菌、肺炎克雷伯菌、A. 鲍曼氏、铜绿假单胞菌和粪肠球菌(ESKAPE)[和糖尿病足感染]病原体的MIC较高 洗必泰优于安慰剂组，b)洗必泰组不会被ESKAPE定植[和 糖尿病足感染]病原菌对关键抗生素的MIC高于安慰剂组。 我们期望获得：1)评估洗必泰作为预防疾病的日常干预措施的可行性。 糖尿病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 长期使用洗必泰。我们的长期目标是测试操控皮肤的干预措施 微生物区系预防足部溃疡在一项更大的(对于临床相关终点有足够的动力)临床试验中 以降低与糖尿病足溃疡相关的截肢风险。

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.