The effectiveness of nitrofurantoin, fosfomycin and trimethoprim for the treatment of cystitis in relation to renal function
Thijs ten Doesschate, Eva van Haren, Rixt A. Wijma, Birgit C. P. Koch, Marc J. M. Bonten, Cornelis H. van Werkhoven
Abstract
OBJECTIVES: We evaluated the effect of renal function on clinical failure rates of nitrofurantoin, fosfomycin and trimethoprim for the treatment of cystitis in primary care. METHODS: Data were retrospectively obtained from 78 Dutch general practitioner (GP) practices between 2013 and 2019. Eligible episodes in patients (>11 years) were those requiring 5 days of nitrofurantoin (NF5), single-dose fosfomycin-trometamol (FT1), 3 days of trimethoprim (TMP3) for uncomplicated cystitis, or 7 days of nitrofurantoin (NF7) or trimethoprim (TMP7) for complicated cystitis. Clinical failure was defined as second antibiotic prescription for cystitis or pyelonephritis within 28 days post-prescription. Mixed effects regression analysis was used, with patient and GP practice as random effects and demography, comorbidity, and cystitis history as fixed effects. RESULTS: Adjusted odds ratios (aORs) for clinical failure per 10mL/min decrease in estimated glomerular filtration rate (eGFR) were 1.05 (95% CI: 1.01-1.09) for NF5 (n = 24,591), 0.96 (95% CI: 0.92-1.01) for FT1 (n = 5359), 0.98 (95% CI: 0.89-1.08) for TMP3 (n = 1064), 1.05 (95% CI: 1.02-1.09) for NF7 (n = 10,628) and 1.02 (95% CI: 0.93-1.14) for TMP7 (n = 831). In uncomplicated cystitis and eGFR ≥60 mL/min, clinical failures occurred in 14.6% (1895/12 980) of NF5-treated, 20.7% (266/1283) of FT1-treated (aOR versus NF5 1.37, 95% CI 1.18-1.59) and 20.8% (66/318) of TMP3-treated patients (aOR 1.42, 95% CI 1.07-1.87 versus NF5). In uncomplicated cystitis and eGFR <60 mL/min, FT1 resulted in 16.0% (39/244) and NF5 in 23.3% clinical failures (110/472), aOR: 0.61, 95% CI: 0.39-0.95). CONCLUSIONS: In eGFR ≥60 mL/min treatment with fosfomycin or trimethoprim for uncomplicated cystitis was associated with more clinical failure than treatment with nitrofurantoin, while in eGFR <60 mL/min nitrofurantoin was associated with more clinical failure than fosfomycin-trometamol. Renal function, if known, should be considered in the clinical decision-making for cystitis treatment.