Identifying Optimal Antibiotic Regimens to Treat Urinary Tract Infections During Pregnancy

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.

Grant Number: 5R01HD107083-05
NIH Institute/Center: NIH
Principal Investigator: Anne Butler