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.

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.

本研究评估了单剂量磷霉素与双剂量磷霉素以及短期疗程的呋喃妥因和匹维溴铵在有尿路感染症状的女性中的有效性和安全性。

Methods

This phase 4, pragmatic, multicentre, parallel-group, open-label, randomised clinical trial was conducted in Spanish primary care centres from 2022 to 2024.

这项第四阶段、实用的、多中心、平行组、开放标签的随机临床试验于2022年至2024年在西班牙初级保健中心进行。

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).

年龄在18岁或以上的女性，至少有一种尿路感染特异性症状（排尿困难、尿急、尿频或耻骨上压痛），并且尿液试纸检测对亚硝酸盐或白细胞酯酶呈阳性，被随机分配（1:1:1:1）到四种治疗方案中的一种：单剂量3克的磷霉素，两个3克剂量的磷霉素，硝呋太尔（每日三次，每次100毫克，连续5天），或匹维西林（每日三次，每次400毫克，连续3天）。

Doctors and patients were not masked to group assignment.

医生和患者均未对分组分配进行盲法处理。

The primary outcome was the proportion of patients with clinical resolution (defined as the disappearance of all infection symptoms) at day 7.

主要结果是第7天时临床症状消失（定义为所有感染症状的消失）的患者比例。

This trial is registered with ClinicalTrials.gov (NCT04959331) and EudraCT (2021-001332-26) and is completed.

该试验已在ClinicalTrials.gov (NCT04959331)和EudraCT (2021-001332-26)注册，并已完成。

Results

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).

在2022年4月4日至2024年11月14日期间评估的804名患者中，有768名患者被随机分配（单剂量磷霉素组191人，双剂量磷霉素组194人，硝呋太尔组190人，匹维溴铵组193人）。

Patients had a median age of 48 years (IQR 34-63).

患者的中位年龄为48岁（四分位数间距34-63岁）。

Race and ethnicity data were not collected.

未收集种族和民族数据。

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).

在纳入主要分析的720名有可用数据的女性中，单剂量磷霉素的临床缓解比例最低（185名患者中有109名，占59%），而呋喃妥因的临床缓解比例最高（172名患者中有128名，占74%；与单剂量磷霉素相比差异为15·5个百分点[95%置信区间5·9至25·1]；p=0·0168），其次是匹维溴铵（182名患者中有127名，占70%；差异为10·9个百分点[1·1至20·6]；p=0·2352）和双剂量磷霉素组（181名患者中有122名，占67%；差异为8·5个百分点[-1·4至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.

在接受单剂量磷霉素治疗的191名患者中，有38名（19·9%[95%置信区间14·9至26·1]）出现不良事件，在接受双剂量磷霉素治疗的194名患者中，有51名（26·3%[20·6至32·9]）出现不良事件，在接受呋喃妥因治疗的190名患者中，有51名（26·8%[21·0至33·6]）出现不良事件，在接受匹维溴铵治疗的193名患者中，有41名（21·2%[16·1至27·5]）出现不良事件。

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).

大多数不良事件为轻度且自行缓解，主要为胃肠道反应。发生了四起严重不良事件，其中一起与研究治疗相关（在 pivmecillinam 组中有一例肾盂肾炎）。

interpretation

Nitrofurantoin was the most effective treatment and single-dose fosfomycin the least effective treatment for UTIs.

硝呋太尔是治疗尿路感染最有效的药物，而单剂量磷霉素是最不有效的治疗药物。

Adverse events were mild.

不良事件较轻微。

The role of fosfomycin as a first-line antibiotic for uncomplicated UTI should be re-evaluated.

应重新评估磷霉素作为无并发症尿路感染一线抗生素的角色。

funding

Carlos III Institute of Health, Spanish Ministry of Science and Innovation, and European Regional Development Fund.

卡洛斯三世健康研究所、西班牙科学技术创新部以及欧洲区域发展基金。