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Nitrofurantoin or Fosfomycin to treat an uncomplicated UTI?


  • Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases have recommended nitrofurantoin and fosfomycin as first-line agents
  • Huttner et al. (JAMA 2018) compare the clinical and microbiologic efficacy of nitrofurantoin and fosfomycin in women with uncomplicated cystitis


  • Randomized clinical controlled trial
  • Participants: Women ≥18 years and older with
    • Symptoms of lower UTI | Positive urine dipstick result | No known resistance to study antibiotics
  • Randomized to two arms
    • Oral nitrofurantoin (100 mg 3 times a day for 5 days)
    • Single 3-g dose of oral fosfomycin
  • Primary outcomes were measured at 14 and 28 days after therapy completion
    • Clinical resolution: Complete resolution without prior failure
    • Failure: Need for additional or change in antibiotic treatment due to UTI or discontinuation due to lack of efficacy
    • Indeterminate: Persistence of symptoms without objective evidence of infection
  • Secondary outcomes included
    • Bacteriologic response and incidence of adverse events


  • 513 patients were randomized
    • median age, 44 years
    • 475 (93%) completed the trial
    • 377 (73%) had a confirmed positive baseline culture
  • Clinical resolution through day 28 was statistically significant in favor of nitrofurantoin
    • 70% of patients receiving nitrofurantoin and 58% of patients receiving fosfomycin
    • Difference of 12% (95% CI, 4%-21%; P = .004)
  • Microbiologic resolution was statistically significant in favor of nitrofurantoin
    • 74% of patients receiving nitrofurantoin and 63% of patients receiving fosfomycin
    • Difference of 11% (95% CI, 1%-20%; P = .04)
  • 28 day data consistent with 14 day findings


  • Clinical response chosen as primary outome as that is what is most meaningful to the patient
  • There may be more baseline resistance to fosfomycin than originally thought
  • Nitrofurantoin success rates were less than expected but study had higher rate of non-E coli then often seen
    • Resistance increasing faster in areas where nitrofurantoin is available over the counter
  • There was a significantly greater likelihood of clinical and microbiological resolution in women with uncomplicated UTI after 5-day nitrofurantoin, compared with a single-dose fosfomycin
  • The accompanying editorial raises concern regarding dosing
    • Recommendation is for nitrofurantoin twice a day
    • Authors used 3 times a day because this is the more prevalent dosing schedule in Europe
  • Despite limitations, the editorial does claim that the overall design and results of this study do suggest that nitrofurantoin is more clinically effectiveness than fosfomycin for acute uncomplicated cystitis among middle-aged women

Learn More – Primary Sources:

Effect of 5-Day Nitrofurantoin vs Single-Dose Fosfomycin on Clinical Resolution of Uncomplicated Lower Urinary Tract Infection in Women A Randomized Clinical Trial

JAMA editorial: Nitrofurantoin vs Fosfomycin – Rendering a Verdict in a Trial of Acute Uncomplicated Cystitis