Infant Antibiotic Resistance and Implications for Therapeutic Decision-making

描述(由申请人提供)：大多数卫生保健决策发生在医生与患者接触的层面，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，或者相关的权衡似乎不利时，为最大化社会结果而建立的指导方针不太可能得到遵循；[1]抗生素处方通常就是这种情况。每个患者层面的抗生素治疗决定都是基于我们如何评估潜在结果的，包括短期好处和风险以及长期风险，包括与细菌对抗生素的耐药性相关的风险。不幸的是，抗生素通常是针对不太可能有细菌病原学的疾病开的；即使是很小的益处可能性似乎也超过了未来抗生素耐药性的增加风险。虽然抗生素对耐药细菌定植的短期影响已经得到证明，但每种治疗方法对未来个人、家庭和社会层面耐药性的总体影响仍然很难量化，而且往往被严重忽视或忽视。[1，2]有关个人和家庭使用抗生素的长期影响的知识可以更好地量化这些未来与耐药性相关的风险，并有助于指导医生和患者的抗生素决策。婴儿出生时就有无菌的鼻咽和胃肠道，但在出生的第一年，就成为耐药微生物的重要储存库；[3，4]这为从拉萨微生物平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，以改善儿科门诊抗生素处方的合理性，具体地说，减少不必要的治疗，将耐药性降至最低，并同时在个人、家庭和社会层面促进良好的长期临床结果。在这项建议中，我们将1)收集一个观察队列，跟踪新生儿在出生第一年暴露于抗生素和特定细菌病原体及其相关抗生素耐药性的纵向定植，2)使用这些数据在更广泛的框架内考虑抗生素决策，纳入行为经济学的原则。这些目标将在多学科培训环境中实现，这种培训环境结合了流行病学和微生物学在卫生服务研究方面的优势。目的1：观察出生一年内细菌的纵向定植和耐药性。主要目标：目标1.1：肺炎链球菌和金黄色葡萄球菌的定植特征。目的：了解产超广谱β-内酰胺酶的革兰氏阴性杆菌及耐第三代头孢菌素肺炎S肺炎和S金黄色葡萄球菌的定植情况。目的：探讨肺炎链球菌、金黄色葡萄球菌、革兰氏阴性杆菌、产超广谱β-内酰胺酶革兰氏阴性杆菌定植与婴幼儿抗生素暴露的关系。次要目标：目标1.4：评估婴儿对抗生素耐药肺炎链球菌、金黄色葡萄球菌、革兰氏阴性肠杆菌、产超广谱β-内酰胺酶细菌和家庭成员抗生素使用的关系。目的1.5：探讨婴幼儿耐药肺炎链球菌、金黄色葡萄球菌、革兰氏阴性肠杆菌和产超广谱β-内酰胺酶细菌的定植与婴幼儿和家庭日托使用的关系。假设1：在生命的第一年，接触抗生素的婴儿比没有接触抗生素的婴儿更容易受到耐药菌的侵袭。假设2：在第一年，有个人或家庭日托或接触抗生素的家庭成员的婴儿比没有这种接触的婴儿在耐药微生物中的定殖率更高。目标2：儿科抗生素使用的经济框架。目标2：描述不同的利益相关者(父母、初级保健医生、专家)如何选择抗生素的使用，以及在哪里可以实施干预措施，以促进明智的使用。通过使这些决策考虑的权衡更加明确，我们可能会阐明如何改进它们，在最大限度地提高预期结果的同时最小化风险。使用AIM 1的数据和决策分析工具，我们将开发一个框架，用于制定关于抗生素处方的患者级决策方法。该框架将考虑成本，包括未来的阻力风险、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者在医学、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供了一个创新的跨学科视角：改善抗生素处方的决策。该计划包括由公认的成功导师进行培训，以培养独特的技能，这些技能可以应用于未来的独立研究。

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.