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The antibiotic nitrofurantoin is commonly used to treat uncomplicated urinary tract infections. However, when this drug is used by patients with reduced kidney function, its urine concentration may be subtherapeutic.We conducted a population-based study of older women (mean age 79 years) in Ontario, Canada, whose estimated glomerular filtration rate was relatively low (median 38 mL/min per 1.73 m2) and for whom 1 of 4 antibiotics had been prescribed for urinary tract infection: nitrofurantoin, ciprofloxacin, norfloxacin or trimethoprim–sulfamethoxazole. We assessed 2 measures of treatment failure in the subsequent 14 days: receipt of a second antibiotic indicated for urinary tract infection and hospital encounter (emergency department visit or hospital admission) with a urinary tract infection. We repeated the analysis for older women with relatively high estimated glomerular filtration rate (median 69 mL/min per 1.73 m2).The baseline characteristics of the 4 antibiotic groups were similar. Relative to nitrofurantoin, the other antibiotics (including ciprofloxacin) were associated with a lower rate of treatment failure among women with relatively low estimated glomerular filtration rate (for ciprofloxacin v. nitrofurantoin: second antibiotic prescription, 130/1989 [6.5%] v. 516/3739 [13.8%], odds ratio [OR] 0.44, 95% confidence interval [CI] 0.36–0.53; hospital encounter, 21/1989 [1.1%] v. 95/3739 [2.5%], OR 0.41, 95% CI 0.25–0.66). However, a similar risk of treatment failure with nitrofurantoin was also observed among women with relatively high estimated glomerular filtration rate. The results were consistent in multiple additional analyses.In this study, the presence of mild or moderate reductions in estimated glomerular filtration rate did not justify avoidance of nitrofurantoin.