Identifying Optimal Antibiotic Regimens to Treat Urinary Tract Infections During Pregnancy

确定治疗妊娠期尿路感染的最佳抗生素方案

基本信息

批准号：
10522361
负责人：
Anne Mobley Butler
金额：
$ 71.89万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2027-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10522361
关键词：
Address Adverse drug event Adverse event Affect Ambulatory Care American College of Obstetricians and Gynecologists Antibiotic Resistance Antibiotic Therapy Antibiotics Antimicrobial Resistance Antimicrobial susceptibility Bacteriuria Benefits and Risks Calendar Cardiac Clinical Clinical Trials Clostridium difficile Congenital Abnormality Data Databases Diarrhea Effectiveness Electronic Health Record Evaluation Exanthema First Pregnancy Trimester Geographic Locations Gestational Age Guidelines Healthcare Systems Hypersensitivity Infant Knowledge Low Birth Weight Infant Microbiology Modernization Neonatal Nitrofurantoin Obesity Observational Study Outcome Outpatients Patients Pattern Pharmaceutical Preparations Population Heterogeneity Predisposition Pregnancy Pregnant Women Premature Birth Premature Labor Pyelonephritis Randomized Clinical Trials Recording of previous events Regimen Research Design Risk Risk Estimate Safety Sample Size Second Pregnancy Trimester Selection for Treatments Sepsis Smoking Status Sulfonamides Teratogens Third Pregnancy Trimester Time Treatment Failure Treatment Protocols Uncertainty Urinary tract infection Uropathogen Variant Woman administrative database antibiotic resistant infections antimicrobial antimicrobial drug beta-Lactams clinical decision-making comparative safety cost efficient early pregnancy effectiveness analysis epidemiology study follow-up improved insight microbiome optimal treatments oral cleft pathogen perinatal complications perinatal outcomes pregnant prevent prospective randomized trial screening guidelines standard care standard of care stillbirth treatment duration treatment risk urinary

项目摘要

PROJECT SUMMARY / ABSTRACT UTIs occur in 8% of pregnant women, affecting ~500,000 women annually in the U.S. Serious maternal and infant consequences include pyelonephritis, sepsis, preterm labor, and low birth weight. Guidelines recommend screening and empirical treatment of UTIs (including asymptomatic bacteriuria) in early pregnancy. This approach has become standard of care, yet there is a lack of rigorous evidence to inform antibiotic selection or duration in pregnant women. Most evidence about the benefits and harms of antibiotic regimens has been generated by randomized clinical trials that excluded pregnant women, and which are further limited by small sample size, short follow-up, and heterogeneous treatments. Despite clear guidelines for non-pregnant women, treatment standards for pregnant women are vague. The American College of Obstetricians and Gynecologists (ACOG) recommends nitrofurantoins and sulfonamides as first-line during the second and third trimesters, but provides no guidance for first trimester management. Uncertainty remains about the teratogenicity of nitrofurantoins and sulfonamides due to limitations of previous observational studies. In addition, ACOG does not define appropriate antibiotic duration, instead recommending the “shortest effective duration.” Overall, the lack of guidance about antibiotic selection and treatment duration leads to substantial practice variation and the potential for harm. For example, clinicians commonly prescribe broad- spectrum agents despite antimicrobial stewardship initiatives that recommend narrow-spectrum agents. Providing optimal antibiotic agents and durations could prevent avoidable adverse events, microbiome disruption, and antibiotic-resistant infections. A comprehensive evaluation using real-world data is needed to quantify the benefits and risks of commonly used antibiotic regimens to treat pregnant women with UTI. We will conduct a non-experimental study to examine the utilization, effectiveness, and safety of several commonly used antibiotic regimens in a real-world setting of diverse pregnant women in the U.S. We will apply modern epidemiological study design and analytic approaches to study almost two million pregnant antibiotic recipients and a subset of their infants, from two national databases as well as EHR data from three regional healthcare systems. Our utilization analysis will use microbiology results to characterize variability in antibiotic prescribing within the context of local uropathogen susceptibility patterns. Our antibiotic effectiveness analyses will provide insight into whether the risks of antibiotic treatment failure outcomes vary by antibiotic regimen. Our safety analyses will compare the risk of birth defects and other perinatal complications by antibiotic regimen. Exploratory analyses will examine additional adverse drug events (e.g., Clostridioides difficile diarrhea). This large study will generate evidence to address critical gaps in knowledge about optimal treatment of UTIs in pregnant women. Our results will inform clinical decision-making and reduce suboptimal antibiotic prescribing, which will ultimately prevent adverse events, improve perinatal outcomes, and minimize antibiotic resistance.

项目摘要 /摘要 UTI发生在8％的孕妇中，每年在美国严重材料中影响约50万妇女婴儿后果包括肾上腺炎，败血症，早产和低出生体重。指南早期对UTI的筛查和经验治疗（包括不对称细菌）怀孕。这种方法已成为护理标准，但是缺乏严格的证据来告知孕妇的抗生素选择或持续时间。关于抗生素的益处和危害的大多数证据治疗方案是由排除孕妇的随机临床试验产生的，这些试验是进一步受样本量，短随访和异质治疗的限制。尽管有明确的准则对于非怀孕妇女，孕妇的治疗标准是选票。美国学院产科医生和妇科医生（ACOG）建议在该期间将硝基氟氨酸和磺酰胺作为第一线第二和第三个三个月，但没有为第一学期管理提供指导。不确定性仍然存在由于先前观察性的局限研究。此外，ACOG不能定义适当的抗生素持续时间，而是建议“最短总的来说，缺乏有关抗生素选择和治疗持续时间的指导导致实质性的差异和危害的潜力。例如，临床医生通常规定了广泛的规定 Spectrum Agents目的地抗菌管理计划，推荐窄光谱代理。提供最佳的抗生素剂和持续时间可以防止可避免的广告事件，微生物组破坏和抗生素抗性感染。需要使用现实世界数据进行全面评估量化常用抗生素治疗uti孕妇的益处和风险。我们将进行非实验研究以检查几种通常的利用，有效性和安全性在美国潜水孕妇的现实环境中使用的抗生素方案，我们将应用现代流行病学研究设计和分析方法，用于研究近200万个怀孕抗生素接受者以及来自两个国家数据库以及来自三个区域医疗保健的EHR数据的一部分系统。我们的利用分析将使用微生物学结果来表征抗生素处方的变异性在局部尿道病易感性模式的背景下。我们的抗生素有效性分析将提供深入了解抗生素衰竭结果是否因抗生素方案而变化。我们的安全分析将比较抗生素方案出生缺陷和其他围产期并发症的风险。探索性分析将检查其他不良药物事件（例如梭状芽胞杆菌艰难梭菌腹泻）。这大型研究将产生证据，以解决有关在孕妇。我们的结果将为临床决策提供信息，并减少次优抗生素处方，这最终将防止不良事件，改善围产期结局并最大程度地减少抗生素耐药性。