Women with uncomplicated lower urinary tract infections (UTIs) experience greater clinical and microbiologic resolution with nitrofurantoin than fosfomycin, according to a new study published in the Journal of the American Medical Association.

The guideline-recommended antibiotics were compared in a randomized controlled trial of 513 patients (median age 44 years) from Switzerland, Poland, and Israel. Participants received either oral macrocrystalline nitrofurantoin (100 mg 3 times daily) for 5 days or a single 3 g dose of oral fosfomycin tromethamine.

At 28 days after treatment, 70% of nitrofurantoin recipients had complete resolution of symptoms compared with 58% of fosfomycin-treated patients, Stephan Harbarth, MD, of Geneva University Hospitals and Faculty of Medicine in Switzerland and colleagues reported. Moreover, 74% vs 63% of recipients, respectively, experienced microbiologic resolution, defined as eradication of the bacterial strain with no recurrence of bacteriuria (less than 103 colony-forming units per mL).

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No serious adverse events occurred. The most common side effects, nausea and diarrhea, developed in 3% and 1% of the nitrofurantoin group and 2% and 1% of the fosfomycin group, respectively. Duration of symptoms (4 vs 3 days) and pyelonephritis (0.4% vs 2%) were not significantly different between the nitrofurantoin and fosfomycin groups, respectively.

Despite its efficacy, nitrofurantoin yielded a lower than expected overall response rate. The team attributed this finding to a high incidence of non-Escherichia coli infections in the cohort. Both Proteus spp and Klebsiella spp exhibit resistance to nitrofurantoin.

In an accompanying editorial, Rupak Datta, MD, PhD, and Manisha Juthani-Mehta, MD, observed: “Outstanding issues remain the optimal nitrofurantoin dosing regimen and whether current recommendations of 100 mg twice daily are equally effective as 100 mg 3 times daily. The role of fosfomycin also requires examination. Clinical and microbiologic responses with alternative fosfomycin prescribing practices, such as fosfomycin 3 g followed by 3 g every 3 days for a total of 3 days, 6 days, or 9 days, for multidrug-resistant uropathogens should be tested.”

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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. JAMA. doi:10.1001/jama.2018.3627 [Published online April 22, 2018.]

Datta R and Juthani-Mehta M. Nitrofurantoin vs fosfomycin: Rendering a verdict in a trial of acute uncomplicated cystitis. JAMA. doi:10.1001/jama.2018.4654 [Published online April 22, 2018.]