Huttner A, et al. - Experts evaluated the clinical and microbiologic effectiveness of nitrofurantoin and fosfomycin in women with uncomplicated cystitis. In contrast with single-dose fosfomycin, 5-day nitrofurantoin led to a significantly greater probability of clinical and microbiologic resolution at 28 days after the end of therapy among women with uncomplicated urinary tract infection (UTI).

Methods

• This was a multinational, open-label, analyst-blinded, randomized clinical trial.
• It included 513 nonpregnant women aged 18 years and older with symptoms of lower UTI (dysuria, urgency, frequency, or suprapubic tenderness), a positive urine dipstick result (with detection of nitrites or leukocyte esterase), and no known colonization or previous infection with uropathogens resistant to the study antibiotics.
• The enrollment was conducted from October 2013 through April 2017 at hospital units and outpatient clinics in Geneva, Switzerland; Lodz, Poland; and Petah-Tiqva, Israel.
• Enrollees were randomly divided in a 1:1 ratio to oral nitrofurantoin, 100 mg 3 times a day for 5 days (n = 255), or a single 3-g dose of oral fosfomycin (n = 258).
• They returned 14 and 28 days following therapy completion for clinical analysis and urine culture collection.
• Clinical response in the 28 days after the end of therapy, defined as clinical resolution (complete resolution of symptoms and signs of UTI without prior failure), failure (need for additional or change in antibiotic treatment due to UTI or discontinuation due to lack of efficacy), or indeterminate (persistence of symptoms without objective evidence of infection) served as the primary outcome.
• Secondary outcomes were bacteriologic response and frequency of adverse events.

Results

• Out of the initial 513 patients (median age, 44 years [interquartile range, 31-64]), 475 (93%) completed the trial and 377 (73%) had a confirmed positive baseline culture.
• The achievement of clinical resolution through day 28 was reported in 171 of 244 patients (70%) receiving nitrofurantoin vs 139 of 241 patients (58%) receiving fosfomycin (difference, 12% [95% CI, 4%-21%]; P=.004).
• Microbiologic resolution was seen in 129 of 175 (74%) vs 103 of 163 (63%), respectively (difference, 11% [95% CI, 1%-20%]; P=.04).
• Few adverse events were seen, and were primarily gastrointestinal; the most common being nausea and diarrhea (7/248 [3%] and 3/248 [1%] in the nitrofurantoin group vs 5/247 [2%] and 5/247 [1%] in the fosfomycin group, respectively).