Nitrofurantoin vs. Fosfomycin for Uncomplicated UTI


Nitrofurantoin and fosfomycin are both recommended by the IDSA guidelines as first-line options in the treatment of uncomplicated cystitis due to their low resistance rates and minimal collateral damage. However, deciding which to choose is often based on convenience or habit, rather than supported by literature. This study was performed to compare sustained clinical resolution and microbiologic response between these two agents in middle-aged women with uncomplicated lower urinary tract infections.

What They Did

  • Design: Multinational, open-label, analyst-blinded, randomized clinical trial
  • Location: Hospitals and clinics in Switzerland, Poland, and Israel
  • Inclusion criteria: Adult women with 1) symptomatic UTI 2) urine dipstick positive for nitrites or leukocyte esterase, 3) no previous uropathogens resistant to study drugs
  • Exclusion criteria: pregnancy/lactation; suspected upper UTI, antibiotic use or UTI symptoms in preceding 4 weeks, indwelling catheter, immunosuppression, ClCr <30ml/min, complicated UTI
  • 255 patients received nitrofurantoin 100 mg 3 times daily for 5 days; 258 patients received a single 3 gm fosfomycin dose (both considered 5-day therapeutic courses)

What They Found

  • 73% had positive baseline urine cultures prior to antimicrobial therapy
  • Pooled culture data: E coli (61%), Klebsiella (7%), Enterococcus (7%), Proteus (5%) 
Primary Outcome

(n = 255) (%)


(n = 258)

P value
Clinical Resolution at 28 days 171/244 (70) 139/241 (58) .004
Secondary Outcomes
Clinical Resolution at 14 days 184/247 (75) 162/247 (66) .03
Bacteriologic success at 28 days 129/175 (74) 103/163 (63) .04
Bacteriologic success at 14 days 146/177 (82) 121/165 (73) .04
  • No difference in other secondary endpoints including duration of symptoms or progression to pyelonephritis/urosepsis

Authors’ Conclusions

Among women with uncomplicated UTI, 5-day nitrofurantoin, compared with single-dose fosfomycin, resulted in a significantly greater likelihood of clinical and microbiologic resolution at 28 days after therapy completion

Lingering Questions

      1. Did the extra 5% of patients having non-infectious etiologies with baseline negative cultures in the fosfomycin group impact the clinical resolution outcomes?
      2. Does nitrofurantoin 100 mg twice daily (IDSA guideline recommended dosing) exhibit similar efficacy as the studied nitrofurantoin 100 mg three times daily regimen?
      3. Would 3- or 5-day fosfomycin dosing be as efficacious as 5-day nitrofurantoin?

Application to Clinical Practice

      1. Continue to base antimicrobial selection on local and patient-specific resistance patterns.
      2. When culture data and patient factors do not preclude use of nitrofurantoin, this is likely the preferred option.
      3. Nitrofurantoin is ok to use in older adults and with creatinine clearance higher than 40 mL/min.
      4. Fosfomycin is commonly selected in ED practice due to ease of dosing. However, consideration should be given to prescribing longer durations of therapy to achieve higher cure rates and prevent microbial resistance.
      5. Fosfomycin is a bit more expensive in the U.S. (~$30/dose) and isn’t always available at all community pharmacies.


Huttner 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. JAMA 2018;319(17):1781-9. PMID 29710295

2 thoughts on “Nitrofurantoin vs. Fosfomycin for Uncomplicated UTI”

  1. Hi PharmERToxguy…pondering the nitrofurantoin dosing…they only mention nitrofurantoin macrocrystalline (which is the old Macrodantin usually dosed 4 times a day)…the product that we commonly use in the US is Macrobid (nitrofurantoin macrocrystal/monohydrate-dosed twice a day). While I couldn’t find the word monohydrate anywhere in the article it still stands that regardless of which product they used it is different dosing than what we’re accustomed to.


    1. Yes, the authors did study the older Macrodantin product dosed three times daily which makes it difficult to compare to either Macrodantin dosed four times daily or Macrobid dosed twice daily as we do in the US. Great catch!


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