Clinical and bacteriological effectiveness of three different short-course antibiotic regimens and single-dose fosfomycin for uncomplicated lower urinary tract infections in women (SCOUT): a pragmatic, multicentre, open-label, randomised clinical trial

Clinical Snapshot

Key Findings

• P Value: p=0.0168 for nitrofurantoin vs single-dose fosfomycin

• Effect Size: 15.5 percentage point difference between nitrofurantoin and single-dose fosfomycin

• Primary Outcome: Clinical resolution at day 7: nitrofurantoin 74% vs pivmecillinam 70% vs two-dose fosfomycin 67% vs single-dose fosfomycin 59%

• Nnt Or Sensitivity: NNT = 7 (95% CI 4-17) for nitrofurantoin vs single-dose fosfomycin

• Confidence Interval: 95% CI 5.9 to 25.1 percentage points

Clinical Application

All antibiotics readily available in Australian primary care with established dosing regimens Aligns with current RACGP guidelines recommending nitrofurantoin as first-line. Results support PBS listing priorities and may influence TGA prescribing information updates Women presenting to Australian general practice with uncomplicated UTI symptoms and positive dipstick

Abstract

BACKGROUND: Most guidelines recommend nitrofurantoin, fosfomycin, and sometimes pivmecillinam for uncomplicated urinary tract infections (UTIs), but direct comparisons between these antibiotics are needed. This study evaluated the effectiveness and safety of a single dose of fosfomycin compared with two doses of fosfomycin and short-course regimens of nitrofurantoin and pivmecillinam in women with UTI symptoms. METHODS: This phase 4, pragmatic, multicentre, parallel-group, open-label, randomised clinical trial was conducted in Spanish primary care centres from 2022 to 2024. Women aged 18 years or older with at least one UTI-specific symptom (dysuria, urinary urgency, urinary frequency, or suprapubic tenderness) and a positive urine dipstick test for either nitrites or leukocyte esterase were randomly assigned (1:1:1:1) to one of four treatments: a single 3 g dose of fosfomycin, two 3 g doses of fosfomycin, nitrofurantoin (100 mg three times per day for 5 days), or pivmecillinam (400 mg three times per day for 3 days). Doctors and patients were not masked to group assignment. The primary outcome was the proportion of patients with clinical resolution (defined as the disappearance of all infection symptoms) at day 7. This trial is registered with ClinicalTrials.gov (NCT04959331) and EudraCT (2021-001332-26) and is completed. FINDINGS: Of the 804 patients assessed for eligibility between April 4, 2022 and Nov 14, 2024, 768 patients were randomly allocated (191 to the single-dose fosfomycin group, 194 to the two-dose fosfomycin group, 190 to the nitrofurantoin group, and 193 to the pivmecillinam group). Patients had a median age of 48 years (IQR 34-63). Race and ethnicity data were not collected. Among the 720 women with available data included in the primary analysis, single-dose fosfomycin had the lowest proportion of clinical resolution (109 [59%] of 185 patients), while nitrofurantoin had the highest (128 [74%] of 172 patients; difference 15·5 percentage points [95% CI 5·9 to 25·1] vs single-dose fosfomycin; p=0·0168), followed by pivmecillinam (127 [70%] of 182; difference 10·9 percentage points [1·1 to 20·6]; p=0·2352) and the two-dose fosfomycin group (122 [67%] of 181; difference 8·5 percentage points [-1·4 to 18·3]; p=0·6935). Adverse events occurred in 38 (19·9% [95% CI 14·9 to 26·1) of 191 patients who received single-dose fosfomycin, 51 (26·3% [20·6 to 32·9]) of 194 who received two-dose fosfomycin, 51 (26·8% [21·0 to 33·6]) of 190 who received nitrofurantoin, and 41 (21·2% [16·1 to 27·5]) of 193 who received pivmecillinam. Most adverse events were mild and self-limiting, primarily gastrointestinal. Four serious adverse events occurred, of which one was related to the study treatment (one case of pyelonephritis in the pivmecillinam group). INTERPRETATION: Nitrofurantoin was the most effective treatment and single-dose fosfomycin the least effective treatment for UTIs. Adverse events were mild. The role of fosfomycin as a first-line antibiotic for uncomplicated UTI should be re-evaluated. FUNDING: Carlos III Institute of Health, Spanish Ministry of Science and Innovation, and European Regional Development Fund.

References

1. 1.Llor, C., Monfà, R., Garcia-Sangenís, A., Leiva, A., Marín-Cañada, J., Sánchez-Calavera, M. A., Moragas, A., Aguilar-Sánchez, M., Troncoso-Mariño, A., Rodríguez-Barrientos, R., Molero, J. M., Ouchi, D., Miranda-Jiménez, C., Fernández-García, S., & Morros, R. (2026). Clinical and bacteriological effectiveness of three different short-course antibiotic regimens and single-dose fosfomycin for uncomplicated lower urinary tract infections in women (SCOUT): a pragmatic, multicentre, open-label, randomised clinical trial. *Lancet*, *407*(10462), 1234-1245. https://doi.org/10.1016/S0140-6736(25)02171-3