TOPLINE

Trimethoprim-sulfamethoxazole (TMP-SMX) was associated with more than 25% higher risk for treatment failure in postmenopausal women with uncomplicated urinary tract infections (UTIs) than nitrofurantoin. Nitrofurantoin and fosfomycin showed similar effectiveness, though nitrofurantoin reduced hospitalization risk by 40% compared with fosfomycin.

METHODOLOGY

• Researchers conducted a retrospective cohort study using the TriNetX database in the US, analyzing data from 67 healthcare organizations with approximately 115 million patients collected between March 2006 and March 2026.
• A total of 236,927 postmenopausal women aged ≥ 40 years with acute uncomplicated cystitis or UTI were included and stratified by initial antibiotic therapy: nitrofurantoin (n = 152,793), TMP-SMX (n = 80,815), or fosfomycin (n = 3319).
• Propensity score matching (1:1) was used to balance demographics, laboratory values (BMI, serum albumin, and A1c), comorbidities (type 2 diabetes mellitus, chronic kidney disease stage 4 or 5, and end-stage renal disease), and prior gynecologic procedures (hysterectomy and oophorectomy).
• The primary outcome was a composite measure of treatment failure within 7 days of treatment initiation, including antibiotic escalation to fluoroquinolones or beta-lactam antibiotics, pyelonephritis, bacteremia, sepsis, hospitalization, critical care services, and mortality.
• Outcomes were compared between matched groups using a two-sided z test for proportions, with risks and relative risk ratios (RRs) calculated and P values adjusted using the Holm-Bonferroni method for multiple comparisons.

TAKEAWAY

• After propensity score matching, TMP-SMX was associated with higher risk for composite treatment failure than nitrofurantoin (10.2% vs 8.0%; RR, 1.28; 95% CI, 1.23-1.32), including higher rates of antibiotic escalation, pyelonephritis, bacteremia, sepsis, hospitalization, critical care services, and mortality.
• Compared with fosfomycin, TMP-SMX was associated with higher risk for composite treatment failure (13.3% vs 9.6%; RR, 1.39; 95% CI, 1.21-1.59), as well as higher rates of sepsis, hospitalization, and critical care services.
• Nitrofurantoin and fosfomycin had similar rates of composite treatment failure (9.0% vs 9.6%; RR, 0.93; 95% CI, 0.80-1.09), although hospitalization was less frequent with nitrofurantoin (1.8% vs 3.0%; RR, 0.60; 95% CI, 0.44-0.82).
• According to the authors, postmenopausal status may represent an underrecognized risk factor for empiric treatment failure, suggesting that age and menopausal status should be considered in the selection of empiric antibiotic therapy.

IN PRACTICE

“Although the direction of association was consistent with findings in premenopausal populations, the underlying contributors to treatment failure may differ specifically in postmenopausal women. Estrogen deficiency alters the urogenital microbiome, including loss of protective lactobacilli and increased colonization by uropathogenic organisms. Resistance patterns in postmenopausal women also differ from those observed in younger, premenopausal populations,” the authors of the study wrote.

SOURCE

The study was led by Bryan T. Oshiro, MD, Riverside University Health System, Moreno Valley, California. It was published online in O&G Open.

LIMITATIONS

As a retrospective analysis, causality cannot be established and findings are subject to misclassification with potential residual confounding. Serum albumin remained modestly imbalanced after matching and may reflect differences in frailty, nutritional status, or underlying illness severity, though the consistency of associations across multiple outcomes suggests this imbalance is unlikely to fully explain the findings. Postmenopausal status was identified with diagnostic codes rather than hormonal measurements, and many postmenopausal women likely lack specific menopause codes and are therefore not captured. Information on clinical factors including UTI history and culture susceptibility results was not uniformly available, and adherence to treatment could not be confirmed.

DISCLOSURES

No disclosures or conflict of interest statements were provided in the study regarding funding sources or financial relationships.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.