Infant Antibiotic Resistance and Implications for Therapeutic Decision-making

婴儿抗生素耐药性及其对治疗决策的影响

• 批准号: 8383248
• 负责人: Sharon B Meropol
• 金额: $ 13.23万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-16 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8383248
• 关键词: Address; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Bacillus (bacterium); Bacteria; Bacterial Antibiotic Resistance; Behavioral; Benefits and Risks; Cephalosporin Resistance; Child; Childhood; Clinical; Communities; Conflict (Psychology); Data; Day Care; Decision Analysis; Decision Making; Development; Disease; Economics; Enteral; Enterobacteriaceae; Environment; Epidemiology; Etiology; Family; Future; Gastrointestinal tract structure; Generations; Goals; Gram-Negative Bacteria; Guidelines; Health Services Research; Healthcare; Household; Incentives; Individual; Infant; Infection; Intervention; Knowledge; Life; Long-Term Effects; Medicine; Mentors; Microbiology; Newborn Infant; Organism; Outcome; Outpatients; Parents; Patients; Physicians; Primary Care Physician; Public Health; Research; Resistance; Risk; Societies; Specialist; Staphylococcus aureus; Sterility; Streptococcus pneumoniae; Therapeutic; Training; bacterial resistance; base; beta-Lactamase; cohort; cost; discount; discounting; improved; innovation; interest; member; multidisciplinary; pathogen; skills; theories; tool

DESCRIPTION (provided by applicant): Most health care decision-making occurs at the level of the physician-patient encounter, where incentives at the patient level often take priority to society. When priorities at the individual vs. the societal levels conflict, or if the involved tradeoffs seem unfavorable, guidelines established to maximize societal outcomes are less likely to be followed; [1] this is often the case with antibiotic prescribing. Each patient level antibiotic treatment decision is based on how we value potential outcomes, including short-term benefits and risks and longer-term risks, including those related to bacterial resistance to antibiotics. Unfortunately, antibiotics are often prescribed for illnesses unlikely to have a bacterial etiology; even a very small likelihood of benefit seems to outweigh an increased risk of future antibiotic resistance. While short-term effects of antibiotics on colonization with resistan bacteria have been demonstrated, the overall implications of each treatment for future individual, family and societal-level resistance remain difficult to quantify, and are often steepl discounted or ignored. [1,2] Knowledge regarding the longer-term effects of personal and household antibiotic use could better quantify these future resistance-related risks, and help guide antibiotic decision-making for physicians and patients. Infants are born with sterile nasopharyngeal and gastrointestinal tracts and yet, during the 1st year of life, become important reservoirs of resistant organisms; [3, 4] this creates an opportunity to study colonization and resistance starting from a microbiological tabula rasa. The overall goal of the proposed research is to develop strategies to improve judicious pediatric outpatient antibiotic prescribing, specifically, to reduce unnecessary treatment, minimize resistance, and promote favorable long-term clinical outcomes, simultaneously at the individual, family, and societal levels. In this proposal, we will 1) assemble an observational cohort, following newborns' antibiotic exposure and longitudinal colonization with specific bacterial pathogens and related antibiotic resistance in the 1st year of life, and 2) use these data to consider antibiotic decision-making within a broader framework, incorporating principles of behavioral economics. These goals will be achieved in a multidisciplinary training environment that combines the strengths of epidemiology and microbiology within the context of health services research. Aim 1: Observational cohort of longitudinal bacterial colonization and resistance in the first year of life. Primary Objectives: Objective 1.1: Characterize colonization with Streptococcus pneumoniae and Staphylococcus aureus. Objective 1.2: Characterize colonization with antibiotic-resistant S pneumoniae and S aureus and 3rd generation cephalosporin resistant and extended-spectrum beta lactamase (ESBL) producing gram-negative enteric bacilli. Objective 1.3: Assess the relationship between colonization with antibiotic-resistant S. pneumoniae, S. aureus, gram negative enteric bacilli, and ESBL-producing gram negative bacteria and infants' antibiotic exposure. Secondary Objectives: Objective 1.4: Assess the relationship between infants' colonization with antibiotic-resistant S. pneumoniae, S. aureus, gram negative enteric bacilli, and ESBL-producing bacteria and household members' antibiotic use. Objective 1.5: Assess the relationship between infants' colonization with antibiotic-resistant S. pneumoniae, S. aureus, gram negative enteric bacteria, and ESBL-producing bacteria, and infant and households daycare use. Hypothesis 1: During the 1st year of life, infants with antibiotic exposure will have greater colonization with resistan organisms than infants without antibiotic exposure. Hypothesis 2: During their 1st year, infants with personal or household day care use or antibiotic-exposed household members will have greater colonization with resistant organisms than those without such exposures Aim 2: Economic framework for pediatric antibiotic use. Objective 2: Describe how different stakeholders (parents, primary care physicians, specialists) make choices regarding antibiotic use, and where interventions to promote judicious use may be implemented. By making the tradeoffs considered for these decisions more explicit, we may clarify how to improve them, maximizing desired outcomes while minimizing risks. Using data from Aim 1 and decision analysis tools, we will develop a framework for an approach to patient-level decision-making regarding antibiotic prescribing. The framework will consider costs including future resistance risks, benefits, externalities (external effects), imperfect information, under-valuing (over-discounting) outcomes, and behavioral economics concepts including Prospect Theory. These interrelated projects exploit the applicant's unique background in medicine, epidemiology, health services research, and economics to present an innovative interdisciplinary perspective for an urgent public health problem: improving decision-making for antibiotic prescribing. The plan includes training by recognized and successful mentors to cultivate unique skills that can be applied in future independent research. PUBLIC HEALTH RELEVANCE: Escalating resistance to antibiotics among disease-causing community bacteria increasingly threatens our ability to treat patients' infections, and young children are a major reservoir of resistant organisms. Antibiotic use contributes to further resistance; while antibiotic use has implications at the societal level, each pediatric antibiotic use decision is made at the physician-patient level, where individual considerations and short-term outcomes often take precedence over societal interests. These two interrelated innovative projects will address an urgent public health issue: understanding the development of bacteria that are resistant to antibiotics within the community, and improving judicious decision-making regarding antibiotic prescribing.

描述（由申请人提供）：大多数医疗保健决策发生在医患接触的层面，其中患者层面的激励往往优先于社会。当个人与社会层面的优先事项发生冲突，或者所涉及的权衡似乎不利时，为最大化社会结果而制定的指导方针就不太可能被遵循；这通常是抗生素处方的情况。每个患者层面的抗生素治疗决策都是基于我们如何评估潜在结果，包括短期收益和风险以及长期风险，包括与细菌对抗生素耐药性相关的风险。不幸的是，抗生素经常被开给不太可能有细菌病因的疾病；即使是非常小的获益可能性似乎也超过了未来抗生素耐药性增加的风险。虽然抗生素对耐药细菌定植的短期影响已经得到证实，但每种治疗对未来个人、家庭和社会层面耐药性的总体影响仍然难以量化，而且往往被大大低估或忽视。[1,2]了解个人和家庭使用抗生素的长期影响可以更好地量化这些未来的耐药性相关风险，并帮助指导医生和患者的抗生素决策。婴儿出生时鼻咽和胃肠道是无菌的，但在出生后的第一年，就成为耐药生物的重要宿主；[3,4]这为从微生物白板开始研究定植和耐药性创造了机会。拟议研究的总体目标是制定策略，以提高明智的儿科门诊抗生素处方，特别是减少不必要的治疗，最大限度地减少耐药性，并促进良好的长期临床结果，同时在个人，家庭和社会层面。在这项提议中，我们将1)组建一个观察队列，跟踪新生儿在出生后第一年的抗生素暴露和特定细菌病原体的纵向定植以及相关的抗生素耐药性，2)使用这些数据在更广泛的框架内考虑抗生素决策，结合行为经济学原理。这些目标将在多学科培训环境中实现，在卫生服务研究的范围内结合流行病学和微生物学的优势。目的1：观察第一年纵向细菌定植和耐药性的队列。目的1.1：描述肺炎链球菌和金黄色葡萄球菌的定植特征。目的1.2：鉴定耐药肺炎链球菌和金黄色葡萄球菌以及产生第三代头孢菌素耐药和广谱β -内酰胺酶（ESBL）的革兰氏阴性肠杆菌的定植。目的1.3：评估耐药肺炎链球菌、金黄色葡萄球菌、革兰氏阴性肠杆菌和产esbl的革兰氏阴性菌定植与婴儿抗生素暴露的关系。次要目的：目的1.4：评估婴儿耐药肺炎链球菌、金黄色葡萄球菌、革兰氏阴性肠杆菌和产esbl细菌定植与家庭成员抗生素使用的关系。目的1.5：评估婴儿与耐抗生素肺炎链球菌、金黄色葡萄球菌、革兰氏阴性肠道细菌和产esbl细菌的定植与婴儿和家庭日托使用的关系。假设1：在出生后的第一年，接触抗生素的婴儿比没有接触抗生素的婴儿有更多的耐药菌定植。假设2：在婴儿出生的第一年，有个人或家庭日托服务的婴儿或有抗生素暴露家庭成员的婴儿比没有这种暴露的婴儿有更大的耐药菌定植。目标2：描述不同的利益相关者（家长、初级保健医生、专家）如何对抗生素的使用做出选择，以及在哪里可以实施促进明智使用的干预措施。通过更明确地考虑这些决策的权衡，我们可以阐明如何改进它们，在最小化风险的同时最大化期望的结果。利用Aim 1的数据和决策分析工具，我们将开发一个关于抗生素处方的患者层面决策方法的框架。该框架将考虑成本，包括未来抵抗风险、收益、外部性（外部效应）、不完全信息、低估（过度贴现）结果，以及包括前景理论在内的行为经济学概念。这些相互关联的项目利用申请人在医学、流行病学、卫生服务研究和经济学方面的独特背景，为一个紧迫的公共卫生问题提出了一个创新的跨学科视角：改进抗生素处方的决策。该计划包括由公认的成功导师进行培训，以培养可用于未来独立研究的独特技能。