[Source: Journal of the American Medical Association, full page: (LINK). Abstract, edited.]
Original Investigation / April 22, 2018
Effect of 5-Day Nitrofurantoin vs Single-Dose Fosfomycin on Clinical Resolution of Uncomplicated Lower Urinary Tract Infection in Women – A Randomized Clinical Trial
Angela Huttner, MD1,2; Anna Kowalczyk, MS3; Adi Turjeman, MSc4; et al Tanya Babich, MSc4; Caroline Brossier, RN1; Noa Eliakim-Raz, MD4,5; Katarzyna Kosiek, MD, PhD6; Begoña Martinez de Tejada, MD, PhD7; Xavier Roux, MD8; Shachaf Shiber, MD9; Ursula Theuretzbacher, PhD10; Elodie von Dach, PhD2,11; Dafna Yahav, MD4,12; Leonard Leibovici, MD4,5; Maciek Godycki-Ćwirko, MD, PhD3,6; Johan W. Mouton, MD, PhD13; Stephan Harbarth, MD1,2
Author Affiliations: 1 Infection Control Program, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland; 2 Division of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland; 3 Centre for Family and Community Medicine, Medical University of Lodz, Lodz, Poland; 4 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 5 Department of Internal Medicine E, Rabin Medical Center, Beilinson Campus, Peta-Tiqva, Israel; 6 Faculty of Health Sciences, Division of Public Health, Medical University of Lodz, Lodz, Poland; 7 Obstetrics Division, Department of Obstetrics and Gynecology, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland; 8 Department of Internal Medicine, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland; 9 Department of Emergency Medicine, Rabin Medical Center, Beilinson Campus, Peta-Tiqva, Israel; 10 Center for Anti-Infective Agents, Vienna, Austria; 11 Clinical Trials Unit, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland; 12 Infectious Diseases Unit, Rabin Medical Center, Beilinson Hospital, Petah-Tiqva, Israel; 13 Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, the Netherlands
JAMA. Published online April 22, 2018. doi:10.1001/jama.2018.3627
- Question – What is the effect of 5-day nitrofurantoin, compared with single-dose fosfomycin, on clinical resolution of uncomplicated lower urinary tract infection (UTI) in women?
- Findings – In this randomized clinical trial that included 513 women with uncomplicated UTI, clinical resolution at 28 days occurred in 70% of patients in the nitrofurantoin group vs 58% of patients in the fosfomycin group, a statistically significant difference.
- Meaning – Five-day nitrofurantoin may be a better alternative to single-dose fosfomycin for treating uncomplicated UTI in women.
The use of nitrofurantoin and fosfomycin has increased since guidelines began recommending them as first-line therapy for lower urinary tract infection (UTI).
To compare the clinical and microbiologic efficacy of nitrofurantoin and fosfomycin in women with uncomplicated cystitis.
Design, Setting, and Participants
Multinational, open-label, analyst-blinded, randomized clinical trial including 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. Recruitment took place from October 2013 through April 2017 at hospital units and outpatient clinics in Geneva, Switzerland; Lodz, Poland; and Petah-Tiqva, Israel.
Participants were randomized 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 after therapy completion for clinical evaluation and urine culture collection.
Main Outcomes and Measures
The primary outcome was clinical response in the 28 days following therapy completion, 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). Secondary outcomes included bacteriologic response and incidence of adverse events.
Among 513 patients who were randomized (median age, 44 years [interquartile range, 31-64]), 475 (93%) completed the trial and 377 (73%) had a confirmed positive baseline culture. Clinical resolution through day 28 was achieved 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 occurred in 129 of 175 (74%) vs 103 of 163 (63%), respectively (difference, 11% [95% CI, 1%-20%]; P = .04). Adverse events were few and primarily gastrointestinal; the most common were 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).
Conclusions and Relevance
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.
Trial Registration ClinicalTrials.gov Identifier: NCT01966653
Keywords: UTI; Nitrofurantoin; Fosfomycin; Antibiotics.