Nitrofurantoin Outperforms TMP-SMX for UTI in Postmenopausal Women: Study
USA: Researchers have found in a new study that Nitrofurantoin was more effective than trimethoprim-sulfamethoxazole (TMP-SMX) for uncomplicated urinary tract infections (UTIs) in postmenopausal women, with TMP-SMX associated with more than 25% higher risk of treatment failure. Nitrofurantoin and fosfomycin had similar overall effectiveness. However, nitrofurantoin reduced the risk of hospitalization by about 40% compared with fosfomycin.
These findings support nitrofurantoin as a preferred option for uncomplicated UTIs in postmenopausal women when clinically appropriate.
The study, published in O&G Open, was conducted by Jhennis Megan Lacsamana of the College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, California, and colleagues. The researchers sought to compare commonly used empiric antibiotic treatments for acute uncomplicated UTI among postmenopausal women using real-world clinical data.
The retrospective cohort study analyzed information from the TriNetX database covering women aged 40 years and older who were identified as menopausal or postmenopausal and developed acute uncomplicated cystitis or UTI between March 2006 and March 2026.
Participants were grouped according to whether they initially received nitrofurantoin, TMP-SMX, or fosfomycin. Researchers assessed treatment failure within seven days of starting antibiotics. The composite outcome included the need for antibiotic escalation, pyelonephritis, bacteremia, sepsis, hospitalization, critical care use, or death.
A total of 236,927 postmenopausal women were included, comprising 152,793 treated with nitrofurantoin, 80,815 with TMP-SMX, and 3,319 with fosfomycin. Statistical matching was performed to account for differences in patient characteristics, laboratory findings, comorbidities, and previous gynecological procedures.
The study led to the following findings:
- Treatment failure occurred in 10.2% of women receiving TMP-SMX versus 8.0% of those receiving nitrofurantoin, indicating a 28% higher relative risk with TMP-SMX.
- TMP-SMX was associated with higher rates of antibiotic escalation, pyelonephritis, bacteremia, sepsis, hospitalization, critical care use, and mortality compared with nitrofurantoin.
- Compared with fosfomycin, TMP-SMX had a higher treatment failure rate (13.3% vs 9.6%) and was also linked to increased risks of sepsis, hospitalization, and critical care use.
- Nitrofurantoin and fosfomycin showed similar overall effectiveness, with treatment failure rates of 9.0% and 9.6%, respectively.
- Hospitalization was less frequent with nitrofurantoin than fosfomycin (1.8% vs 3.0%), corresponding to an approximately 40% lower relative risk.
The researchers cautioned that the retrospective design prevents establishing causality, while residual confounding and possible misclassification of menopausal status may have influenced the results. Data on previous UTIs, antibiotic susceptibility, and treatment adherence were also limited.
However, the large real-world cohort and consistent findings across multiple outcomes support the results. Future prospective studies incorporating microbiological and susceptibility data are needed to better understand treatment response in postmenopausal women.
Overall, the findings suggest that menopausal status may be an important consideration when selecting empiric antibiotics for uncomplicated UTI, with nitrofurantoin and fosfomycin appearing to offer more favorable short-term outcomes than TMP-SMX when clinically appropriate.
Reference:
Johnson, R., Han, B., Lepe, K., Canumay, S., Lacsamana, J. M., & Oshiro, B. T. (2026). Comparative Effectiveness of Empiric Antibiotics for Uncomplicated Urinary Tract Infection in Postmenopausal Women. O&G Open, 3(4). https://doi.org/10.1097/og9.0000000000000191
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