In women with uncomplicated urinary tract infections (UTI), 5-day nitrofurantoin resulted in the significantly greater likelihood of clinical and microbiologic resolution 28 days after therapy completion compared with single-dose fosfomycin, according to research published in the Journal of the American Medical Association.
In this multinational open-label analyst-blinded trial (ClinicalTrials.gov: NCT01966653), non-pregnant women, age >18 with symptoms of lower UTI, a positive urine dipstick result, and no known infections with uropathogens resistant to study medications were enrolled. Participants were randomly assigned on a 1:1 basis to oral nitrofurantoin 100 mg 3 times/day for 5 days (n=255) or a single 3-g dose of oral fosfomycin (n=258). Follow-up was conducted 14 and 28 days post therapy completion.
Clinical resolution through day 28 was observed in 70% of patients receiving nitrofurantoin and 58% of patients receiving fosfomycin (difference 12%; 95% CI, 4%-21%; P =.004). In the nitrofurantoin group, 74% of patients achieved microbiologic resolution compared with 63% of patients in the fosfomycin groups (difference 11%; 95% CI, 1%-20%; P =.04). Few adverse events were reported and these were mainly gastrointestinal in nature. Nausea and diarrhea occurred in 3% and 1% of the nitrofurantoin patients, respectively, and 2% and 1% of the fosfomycin group.
There were several limitations to the study, mainly that the necessity of an open design due to budget concerns may have introduced some measurement bias and laboratory analysis was not centralized, again potentially introducing bias. Political events had an impact on recruitment and follow-up at the study site in Israel, that meaning original targets were not met. In addition, some study site differences in age and local resistance prevalences were observed at the site in Poland due to the availability of over-the-counter nitrofurantoin derivatives.
Investigators were able to conclude that both treatment options had few adverse events and the 5-day course of nitrofurantoin achieved greater likelihood of clinical and microbiologic resolution.
Huttner A, Kowalczyk A, Turjeman A, et al. Effect of 5-day nitrofurantoin vs single-dose fosfomycin on clinical resolution of uncomplicated lower urinary tract infection in women a randomized clinical trial [published online April 22, 2018]. JAMA. doi:10.1001/jama.2018.3627