Clinical Trial of Prophylactic Antibiotics for Children*

描述(由申请人提供)： 项目概述：尿路感染(UTI)是儿童最常见的严重细菌感染，6岁前约有3%的儿童受到影响。目前对患有尿路感染的幼儿的护理标准是进行排尿膀胱尿路造影(VCUG)以评估是否存在膀胱输尿管反流(VUR)，这种情况出现在大约30%-40%的尿路感染儿童中，被认为会增加肾脏瘢痕形成的风险。传统上，VCUG确诊为VUR的儿童每天接受预防性抗生素治疗，直到VUR消失，或接受手术矫正VUR。最近，VUR在促进肾瘢痕形成中的作用以及VCUG、预防性抗生素和VUR手术的有效性受到了质疑。人们还对VCUG和每日预防性抗生素的成本和潜在危害提出了担忧。在这项U01申请中，我们提出了一项多中心、集中随机、双盲、安慰剂对照的等效性试验，以确定在迅速识别UTI症状和确诊UTI早期治疗的情况下，预防性抗生素在减少肾脏疤痕方面是否比安慰剂更好；以及在UTI出现时，DMSA证据显示的肾脏瘢痕形成或肾盂肾炎是否改变了预防性抗生素的效果。我们还将确定抗生素预防是否会增加耐药大肠埃希菌和克雷伯氏菌在胃肠道(G1)的定殖率。和假单胞菌Gl定殖。认识到为U01选择的临床试验中心(CTC)实施的方案将通过Concount[原文如此]开发，本应用程序还描述了费城儿童医院(CHOP)作为NIDDK的膀胱输尿管反流临床研究的潜在CTC所带来的优势。这包括(1)在大型临床研究中招募和留住患者的内容领域的专业知识和经验，(2)可从中招募患者的初级保健和泌尿外科实践的庞大儿科保健网络，(3)适合识别潜在参与者的全网最先进的可搜索电子病历和账单系统，以及(4)进行最高质量临床研究的机构承诺和基础设施。 相关性：这项试验有可能对美国每年数以万计的尿路感染儿童的诊断工作和管理产生重大影响

DESCRIPTION (provided by applicant): Project Summary: Urinary tract infection (UTI) is the most common serious bacterial infection in childhood, affecting approximately 3% of all children by six years of age. The current standard of care for young children who present with UTI is to perform a voiding cystourethrogram (VCUG) to evaluate for the presence of vesicoureteral reflux (VUR), a condition that is present in approximately 30-40% of children with UTI and is thought to increase the risk of renal scarring. Traditionally, children with VUR identified on VCUG are treated with daily prophylactic antibiotics until the VUR resolves, or have surgical correction of the VUR. Recently the role of VUR in contributing to renal scarring and the utility of VCUG, prophylactic antibiotics and VUR surgery have been questioned. Concerns have also been raised about the cost and potential harms of VCUGs and daily prophylactic antibiotics. In this U01 application we propose a multi-center, centrally randomized, double-blind, placebo-controlled, equivalence trial to determine whether, in the setting of prompt recognition of UTI symptoms and early treatment of confirmed UTI, prophylactic antibiotics are better than placebo in reducing renal scarring; and whether DMSA evidence of renal scarring or pyelonephritis at presentation of UTI modifies the effect of prophylactic antibiotics. We will also determine whether antibiotic prophylaxis increases the rate of gastrointestinal (Gl) colonization with antibiotic resistant E.coli and Klebsiella spp. and Gl colonization with Pseudomonas spp. Recognizing that the protocols implemented by the Clinical Trial Centers (CTCs) selected for this U01 will be developed by concensus [sic], this application also describes the strengths that the Children's Hospital of Philadelphia (CHOP) brings as a potential CTC in the NIDDK's Clinical Study of Vesicoureteral Reflux. These include (1) content area expertise and experience recruiting and retaining patients in large clinical studies, (2) a vast pediatric healthcare network of primary care and urology practices from which to recruit patients, (3) a network-wide state-of-the-art searchable electronic medical record and billing system suitable for identifying potential participants, and (4) an institutional commitment to and infrastructure for conducting the highest quality clinical research. Relevance: The trial has the potential to substantially impact the diagnostic work-up and management for the tens of thousands of children in the US who develop UTIs each year