Comparative Safety of Antibiotics for Common Bacterial Infections During Pregnancy

妊娠期常见细菌感染抗生素的比较安全性

• 批准号: 10391036
• 负责人: Yanmin Zhu
• 金额: $ 64.57万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-02 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10391036
• 关键词: Address; Advisory Committees; Age; Antibiotic Therapy; Antibiotics; Area; Bacterial Infections; Benefits and Risks; Cellulitis; Centers for Disease Control and Prevention (U.S.); Cephalosporins; Chlamydia; Clindamycin; Clinical; Conflict (Psychology); Confounding Factors (Epidemiology); Congenital Abnormality; Data; Data Sources; Databases; Ensure; Evaluation; Exposure to; Fetus; Fluoroquinolones; Fosfomycin; Goals; Gonorrhea; Human; Infection; Lower Respiratory Tract Infection; Macrolides; Medicaid; Neonatal; Neonatal Jaundice; Neonatal Mortality; Nitrofurantoin; Observational Study; Outcome; Penicillins; Pharmaceutical Preparations; Pregnancy; Pregnancy Outcome; Pregnant Women; Preventive service; Research; Residual state; Respiratory Tract Infections; Risk; Safety; Sexually Transmitted Diseases; Signal Transduction; Specific qualifier value; Spontaneous abortion; Teratogens; Tetracyclines; Toxic effect; Trimethoprim-Sulfamethoxazole; United States Food and Drug Administration; Urinary tract infection; Vulnerable Populations; Woman; adverse maternal outcomes; adverse outcome; animal data; antimicrobial; cohort; comparative safety; comparison group; detection method; disability; early pregnancy; fetal; malformation; medication safety; member; neonatal morbidity; novel; optimal treatments; pregnant; prenatal exposure; prevent; reproductive; skin abscess; treatment strategy; vaccine safety

The most common bacterial infections during pregnancy include urinary tract infections, cellulitis and skin abscesses, upper and lower respiratory tract infections, and sexually transmitted diseases. Management of bacterial infections in pregnant women requires early antimicrobial treatment to prevent adverse maternal and pregnancy outcomes. As such, antibiotics are among the most commonly used medications in pregnancy – approximately six out of ten publicly insured and four out of ten commercially insured pregnant women fill at least one antibiotic prescription during pregnancy. To select the optimal antibiotic from the range of available options for specific infections, it is therefore crucial to understand the comparative safety of in utero exposure to specific antibiotics. Unfortunately, rigorous and comprehensive safety data to inform the risk-benefit trade-off are sparse and evidence is conflicting. The primary concern among potential risks associated with antibiotic use in pregnancy are congenital malformations, which are a leading cause of neonatal morbidity and mortality, and frequently cause lifelong disability. Additionally, some studies have pointed to an increased risk of spontaneous abortions and neonatal jaundice associated with some commonly used classes of antibiotics. Given that 45% of pregnancies in the US are unintended, understanding the comparative safety of antibiotics in early pregnancy may also inform the selection of antibiotics in women of reproductive age. The objective of the proposed studies is therefore to evaluate the comparative safety of antibiotics commonly used for the treatment of bacterial infections during pregnancy. To accomplish this, we will employ large pregnancy cohorts of publicly and privately insured pregnant women (N ≈ 4.5 million). For each of the most common bacterial infections, we will assess the comparative safety of available commonly used antibiotic treatment options and utilize the rich information in our data sources to control for potential confounding variables. The large study size will enable quantification of effects for the pre-specified outcomes (i.e., malformations overall, specific malformation types, spontaneous abortion, and neonatal jaundice) with great precision. In addition, to ensure a comprehensive evaluation of the comparative safety, we will utilize a novel signal detection method developed by members of our team, TreeScan, for simultaneous evaluation of a broad range of potential maternal, fetal and neonatal adverse outcomes. By harnessing the power of existing real-world data, this study will inform strategies for tailoring antibiotic treatment to optimize pregnancy outcomes in this vulnerable population. As such, the proposed study aligns well with the main goal of PAR-20-300. By defining the safest treatment options for women of reproductive age with bacterial infections, the findings of this study will have direct and immediate clinical impact.

怀孕期间最常见的细菌感染包括尿路感染、蜂窝组织炎和皮肤 腹泻、上呼吸道和下呼吸道感染以及性传播疾病。管理 孕妇的细菌感染需要早期抗菌治疗，以防止不良的孕产妇和 妊娠结局。因此，抗生素是怀孕期间最常用的药物之一- 大约十分之六的公共保险孕妇和十分之四的商业保险孕妇填写了 怀孕期间至少服用一种抗生素。 因此，从针对特定感染的可用选项中选择最佳抗生素至关重要。 了解子宫内暴露于特定抗生素的相对安全性。不幸的是，严格和 全面的安全性数据，以告知风险-效益权衡是稀缺的，证据是相互矛盾的。的 妊娠期使用抗生素的潜在风险主要是先天性的 畸形是新生儿发病率和死亡率的主要原因， 残疾。此外，一些研究指出，自然流产和新生儿流产的风险增加。 与一些常用抗生素有关的黄疸。鉴于美国45%的孕妇 是无意的，了解抗生素在怀孕早期的相对安全性也可以告知 育龄妇女抗生素的选择。 因此，拟议研究的目的是评价抗生素的比较安全性， 用于治疗怀孕期间的细菌感染。为了实现这一目标，我们将采用大量 公共和私人保险孕妇的怀孕队列（450万奈拉）。对于每一个最 常见细菌感染，我们将评估现有常用抗生素的相对安全性 治疗方案，并利用我们数据源中的丰富信息来控制潜在的混杂因素 变量大规模的研究将能够量化预先规定的结局的影响（即， 总体畸形、特定畸形类型、自然流产和新生儿黄疸）， 精度此外，为了确保对比较安全性的全面评价，我们将利用一种新的 我们的团队TreeScan成员开发的信号检测方法，用于同时评估广泛的 一系列潜在的母体、胎儿和新生儿不良结局。 通过利用现有的真实世界数据的力量，这项研究将为定制抗生素的策略提供信息。 治疗，以优化这一弱势群体的妊娠结局。因此，拟议的研究符合 主要目标是PAR-20-300。通过为育龄妇女确定最安全的治疗方案， 对于细菌感染，这项研究的结果将有直接和即时的临床影响。