Identifying Optimal Antibiotic Regimens to Treat Urinary Tract Infections During Pregnancy

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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.