Abstract
ObjectivesGuidelines do not distinguish between 50 mg or 100 mg nitrofurantoin as daily prophylaxis for recurrent urinary tract infection (UTI), although 50 mg might have a better safety profile. Our objective was to compare the effectiveness and safety of both regimens. MethodsData were retrospectively collected from 84 Dutch GP practices between 2013 and 2020. Nitrofurantoin prescriptions of 100 mg and 50 mg every 24 hours in women were included. Cox proportional hazard regression analysis was used to calculate hazard ratios on first episode of UTI, pyelonephritis and (adverse) events. Patients were followed for the duration of consecutive repeated prescriptions, assuming non-informative right censoring, up to 1 year. ResultsNitrofurantoin prophylaxis was prescribed in 1893 patients. Median lengths of follow up were 90 days (interquartile range (IQR) 37–179 days) for 100 mg (n = 551) and 90 days (IQR 30–146 days) for 50 mg (n = 1342) with few differences in baseline characteristics between populations. Under 100 mg and 50 mg, 82/551 (14.9%) and 199/1342 (14.8%) developed UTI and 46/551 (8.3%) and 81/1342 (6.0%) developed pyelonephritis, respectively. Adjusted HRs of 100 mg versus 50 mg were 1.01 (95% CI 0.78–1.30) on first UTI, 1.37 (95% CI 0.95–1.98) on first pyelonephritis episode, 1.82 (95% CI 1.20–2.74) on first consultation for cough, 2.68 for dyspnoea (95% CI 1.11–6.45) and 2.43 for nausea (95% CI 1.03–5.74). ConclusionDaily prophylaxis for recurrent UTI with 100 mg instead of 50 mg nitrofurantoin was associated with an equivalent hazard on UTI or pyelonephritis, and a higher hazard on cough, dyspnoea and nausea. We recommend 50 mg nitrofurantoin as daily prophylaxis.
Highlights
Nitrofurantoin is frequently used as prophylaxis for recurrent urinary tract infection (UTI) [1,2]
The results of this study constitute an important indication that the use of 100 mg compared with 50 mg nitrofurantoin is associated with an increased hazard for pulmonary events and nausea, but an equivalent hazard for first UTI or pyelonephritis
No head-to-head comparisons have been made between the effectiveness or safety of 100 mg and 50 mg nitrofurantoin as UTI prophylaxis
Summary
Nitrofurantoin is frequently used as prophylaxis for recurrent urinary tract infection (UTI) [1,2]. Non-antimicrobial strategies to prevent UTI recurrences are preferable with regard to antimicrobial resistance and adverse events, the use of antimicrobial prophylaxis is still needed in daily practice [3e6]. The efficacy of nitrofurantoin as daily prophylaxis has been well established in multiple randomized controlled trials with an estimated reduction in the risk of UTI of more than 50% compared with placebo [8,9,11]. The Dutch guideline advises prescription of nitrofurantoin for no longer than 12 months [1], because prolonged use seems to be associated with the occurrence of severe adverse events, including pulmonary toxicity [8,12,13]
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