Re: ‘The effectiveness of nitrofurantoin, fosfomycin and trimethoprim for the treatment of cystitis in relation to renal function’ by ten Doesschate et al.
Authors: S. Karakonstantis
Journal: Clinical Microbiology and Infection (2020)

I read with interest the recently published article by Doesschate et al. [[1]Doesschate Tt van Haren E. Wijma R.A. Koch B.C.P. Bonten M.J.M. van Werkhoven C.H. The effectiveness of nitrofurantoin, fosfomycin and trimethoprim for the treatment of cystitis in relation to renal function.Clin Microbiol Infect. 2020; 26: 1355-1360https://doi.org/10.1016/j.cmi.2020.03.001Abstract Full Text Full Text PDF Scopus (12) Google Scholar] suggesting that fosfomycin may be a more effective treatment option than nitrofurantoin for uncomplicated cystitis in patients with an eGFR below 60 mL/min. However, according to other studies, mild/moderate reduction in eGFR (30–60 mL/min) was not associated with decreased efficacy of nitrofurantoin [2Singh N. Gandhi S. McArthur E. Moist L. Jain A.K. Liu R.A. et al.Kidney function and the use of nitrofurantoin to treat urinary tract infections in older women.CMAJ. 2015; 187: 648-656Crossref PubMed Scopus (32) Google Scholar, 3Cunha B.A. Cunha C.B. Lam B. Giuga J. Chin J. Zafonte V.F. et al.Nitrofurantoin safety and effectiveness in treating acute uncomplicated cystitis (AUC) in hospitalized adults with renal insufficiency: antibiotic stewardship implications.Eur J Clin Microbiol Infect Dis. 2017; 36: 1213-1216Crossref PubMed Scopus (16) Google Scholar, 4Geerts A.F. Eppenga W.L. Heerdink R. Derijks H.J. Wensing M.J.P. Egberts T.C.G. et al.Ineffectiveness and adverse events of nitrofurantoin in women with urinary tract infection and renal impairment in primary care.Eur J Clin Pharmacol. 2013; 69: 1701-1707Crossref PubMed Scopus (35) Google Scholar]. As the authors acknowledge, the lack of microbiological data is an important limitation of their study, especially considering that chronic kidney disease may be associated with a higher risk of infection by resistant pathogens [[5]Sogaard M. Heide-Jorgensen U. Vandenbroucke J.P. Schonheyder H.C. Vandenbroucke-Grauls C. Risk factors for extended-spectrum beta-lactamase-producing Escherichia coli urinary tract infection in the community in Denmark: a case–control study.Clin Microbiol Infect. 2017; 23: 952-960Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar]. In one study, for example, most treatment failures with nitrofurantoin (five of eight) in patients with uncomplicated cystitis and eGFR <60 mL/min were due to infections by bacteria intrinsically resistant to nitrofurantoin (e.g. Proteus spp) [[3]Cunha B.A. Cunha C.B. Lam B. Giuga J. Chin J. Zafonte V.F. et al.Nitrofurantoin safety and effectiveness in treating acute uncomplicated cystitis (AUC) in hospitalized adults with renal insufficiency: antibiotic stewardship implications.Eur J Clin Microbiol Infect Dis. 2017; 36: 1213-1216Crossref PubMed Scopus (16) Google Scholar]. When comparing antibiotics in patients with decreased renal function, differences in antimicrobial resistance rates between the compared antibiotics can be an important source of bias. For example, if with decreasing renal function the rate of resistance to nitrofurantoin is higher than the rate of resistance to fosfomycin, this could have significantly biased the results in favor of fosfomycin. Therefore, conclusions regarding the effect of renal function on the efficacy of antibiotics for cystitis cannot be drawn in the absence of antimicrobial susceptibility data. The author declares no conflict of interest. No funding was received for this work. The effectiveness of nitrofurantoin, fosfomycin and trimethoprim for the treatment of cystitis in relation to renal functionClinical Microbiology and InfectionVol. 26Issue 10PreviewWe evaluated the effect of renal function on clinical failure rates of nitrofurantoin, fosfomycin and trimethoprim for the treatment of cystitis in primary care. Full-Text PDF Open Access‘The effectiveness of nitrofurantoin, fosfomycin and trimethoprim for the treatment of cystitis in relation to renal function’ – Author’s replyClinical Microbiology and InfectionVol. 26Issue 10PreviewWe thank our colleagues for their interest in our publication. We disagree with their suggestion that antimicrobial resistance is a potential confounder when assessing the effect of renal function on the efficacy of antibiotics in cystitis. Full-Text PDF Open Archive