Quantifying the impact of vaccines on antibiotic use for respiratory infections in children

项目摘要 抗生素耐药性是对人类健康的重大威胁。人类治疗性抗生素的使用， 发生在非严重感染的门诊环境中，是耐药性的主要、可改变的驱动因素。急性 呼吸道感染（阿里斯）占门诊抗生素使用的很大比例， 被认为是对抗抗生素使用和耐药性的重要机制，特别是对于阿里斯。然而，在这方面， 在了解常见呼吸道病原体对门诊抗生素的贡献方面仍存在不确定性， 使用和量化疫苗的全部潜力，以减少抗生素的使用，阻碍知情决策， 确定疫苗研究和开发的优先事项。拟议的研究解决了这些差距， 针对儿童三种常见呼吸道病原体的现有和正在研制的疫苗：链球菌 肺炎病毒、流感病毒和呼吸道合胞病毒（RSV）。这项拟议工作的目标是 估计现有和潜在疫苗策略对阿里斯门诊抗生素处方的影响 小儿具体而言，本研究的主要目的是：1）估计归因分数 由于疫苗可预防的呼吸道病原体导致的ARI相关儿科门诊抗生素使用; 2） 评价肺炎球菌疫苗接种策略对儿童阿里斯门诊抗生素使用的影响; 3)评价病毒（流感、RSV）疫苗接种策略对阿里斯门诊抗生素使用的影响， 孩子该项目特别关注儿童中的阿里斯，因为它们都是门诊抗生素的主要驱动因素 现有和正在研制的疫苗的用途和目标。这项工作将利用多个，互补，大规模 数据来源包括索赔数据（Optum Clinformatics、IBM MarketScan）和国家代表性数据 门诊医疗调查（全国门诊医疗调查和全国医院门诊医疗调查） 护理调查），每年都有数百万的儿科ARI就诊和门诊抗生素处方，以解决 这些目标。在这项拟议的研究中使用的数据、统计和流行病学方法的广度将 使人们能够对疫苗减少门诊抗生素的潜力有一个新的全面的了解 用于儿童阿里斯。这项工作将为迫切需要的抗生素耐药性缓解策略提供信息， 疫苗研究/开发和政策的优先事项设定和决策。所提出的方法将 进一步提供了一种新的框架，用于评估当前和未来的疫苗作为门诊感染， 抗生素的使用通常不被视为终点，尽管其负担很大。这项研究将是 我提出的培训计划强调发展和经验， 流行病学和统计方法，大数据方法和应用，主题专业知识，以及 成为独立调查员所需的额外技能。加州大学伯克利分校，特别是学校 提供广泛的资源和支持，使我能够成功地完成拟议的 奖学金和实现我的长期目标，成为一个研究导向的传染病流行病学家。

PROJECT SUMMARY Antibiotic resistance is a significant threat to human health. Human therapeutic antibiotic use, the majority of which occurs in outpatient settings for non-severe infections, is a major, modifiable driver of resistance. Acute respiratory infections (ARIs) account for large proportions of outpatient antibiotic use and vaccines have been recognized as important mechanisms to combat antibiotic use and resistance, especially for ARIs. However, uncertainties remain in understanding the contributions of common respiratory pathogens to outpatient antibiotic use and quantifying the full potential of vaccines to reduce antibiotic use, impeding informed policymaking and priority-setting for vaccine research and development. The proposed research addresses these gaps in the context of both existing and pipeline vaccines for three common respiratory pathogens in children: Streptococcus pneumonaie, influenza virus, and respiratory syncytial virus (RSV). The objective of this proposed work is to estimate impacts of both existing and potential vaccine strategies on outpatient antibiotic prescriptions for ARIs in children. More specifically, the research focuses on the following aims: 1) estimate the attributable fractions of ARI-associated pediatric outpatient antibiotic use due to vaccine-preventable respiratory pathogens; 2) evaluate the impact of pneumococcal vaccination strategies on outpatient antibiotic use for ARIs in children; and 3) evaluate the impact of viral (influenza, RSV) vaccination strategies on outpatient antibiotic use for ARIs in children. This project focuses specifically on ARIs in children as they are both major drivers of outpatient antibiotic use and targets of existing and pipeline vaccines. The work will leverage multiple, complementary, large-scale data sources including both claims data (Optum Clinformatics, IBM MarketScan) and nationally-representative outpatient medical surveys (National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey), each with millions of pediatric ARI visits and outpatient antibiotic prescriptions per year, to address these aims. The breadth of data and statistical and epidemiologic methods used in this proposed research will enable a novel and comprehensive understanding of the potential for vaccines to reduce outpatient antibiotic use for ARIs in children. This work will inform urgently-needed antibiotic resistance mitigation strategies and priority setting and decision-making for vaccine research/development and policy. The proposed methods will further provide a novel framework for evaluating current and future vaccines as outpatient infections and antibiotic use are not commonly considered endpoints, despite their substantial burden. This research will be enhanced by and complementary to my proposed training plan, which emphasizes development and experience in epidemiologic and statistical methods, big data methods and applications, subject matter expertise, and additional skills necessary for me to become an independent investigator. UC Berkeley, particularly the School of Public Health, provides extensive resources and support to enable me to successfully complete the proposed fellowship and fulfill my long-term goal of becoming a research-oriented infectious disease epidemiologist.