Identifying Optimal Antibiotic Regimens to Treat Urinary Tract Infections During Pregnancy

项目总结/摘要 UTI发生在8%的孕妇中，在美国每年影响约500，000名妇女。 婴儿的后果包括肾盂肾炎、败血症、早产和低出生体重。准则 建议在早期筛查和经验性治疗尿路感染（包括无症状菌尿） 怀孕这种方法已经成为标准的护理，但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 方案已产生的随机临床试验，排除孕妇， 进一步受到样本量小、随访时间短和治疗异质性的限制。尽管有明确的指导方针 对于非孕妇，孕妇的治疗标准模糊不清。The American College of 妇产科医师（ACOG）建议呋喃妥因和磺胺类药物作为一线治疗， 中期和晚期妊娠，但没有提供早期妊娠管理的指导。不确定性仍然 关于呋喃妥因和磺胺类药物的致畸性，由于以前观察的局限性， 问题研究此外，ACOG没有定义适当的抗生素使用时间，而是建议使用“最短”抗生素。 有效期限”。总的来说，缺乏抗生素选择和治疗持续时间的指导， 实质性的实践变化和潜在的危害。例如，临床医生通常会开出广泛的处方- 尽管抗菌管理倡议建议使用窄谱药物， 提供最佳的抗生素制剂和持续时间可以预防可避免的不良事件，微生物组 破坏和抗药性感染。需要使用真实世界数据进行全面评估， 量化常用抗生素治疗孕妇UTI的益处和风险。我们将 进行一项非实验性研究，以检查几种常用药物的利用率、有效性和安全性。 在美国不同孕妇的真实环境中使用抗生素方案。 流行病学研究设计和分析方法，研究近200万妊娠抗生素接受者 和他们的婴儿的子集，来自两个国家数据库以及来自三个地区医疗保健的EHR数据。 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 在当地泌尿系病原体易感性模式的背景下。我们的抗生素有效性分析将提供 深入了解抗生素治疗失败的风险是否因抗生素方案而异。我们的安全 分析将比较不同抗生素方案的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药物不良事件（例如，艰难梭菌腹泻）。这 一项大型研究将提供证据，以填补关于UTI最佳治疗知识的关键空白， 孕妇我们的研究结果将为临床决策提供信息，并减少次优抗生素处方， 这将最终预防不良事件，改善围产期结果，并最大限度地减少抗生素耐药性。

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.