Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota.
University of Minnesota Medical School, Minneapolis.
JAMA. 2021 Jul 27;326(4):324-331. doi: 10.1001/jama.2021.9899.
Determination of optimal treatment durations for common infectious diseases is an important strategy to preserve antibiotic effectiveness.
To determine whether 7 days of treatment is noninferior to 14 days when using ciprofloxacin or trimethoprim/sulfamethoxazole to treat urinary tract infection (UTI) in afebrile men.
DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled noninferiority trial of afebrile men with presumed symptomatic UTI treated with ciprofloxacin or trimethoprim/sulfamethoxazole at 2 US Veterans Affairs medical centers (enrollment, April 2014 through December 2019; final follow-up, January 28, 2020). Of 1058 eligible men, 272 were randomized.
Participants continued the antibiotic prescribed by their treating clinician for 7 days of treatment and were randomized to receive continued antibiotic therapy (n = 136) or placebo (n = 136) for days 8 to 14 of treatment.
The prespecified primary outcome was resolution of UTI symptoms by 14 days after completion of active antibiotic treatment. A noninferiority margin of 10% was selected. The as-treated population (participants who took ≥26 of 28 doses and missed no more than 2 consecutive doses) was used for the primary analysis, and a secondary analysis included all patients as randomized, regardless of treatment adherence. Secondary outcomes included recurrence of UTI symptoms and/or adverse events within 28 days of stopping study medication.
Among 272 patients (median [interquartile range] age, 69 [62-73] years) who were randomized, 100% completed the trial and 254 (93.4%) were included in the primary as-treated analysis. Symptom resolution occurred in 122/131 (93.1%) participants in the 7-day group vs 111/123 (90.2%) in the 14-day group (difference, 2.9% [1-sided 97.5% CI, -5.2% to ∞]), meeting the noninferiority criterion. In the secondary as-randomized analysis, symptom resolution occurred in 125/136 (91.9%) participants in the 7-day group vs 123/136 (90.4%) in the 14-day group (difference, 1.5% [1-sided 97.5% CI, -5.8% to ∞]) Recurrence of UTI symptoms occurred in 13/131 (9.9%) participants in the 7-day group vs 15/123 (12.9%) in the 14-day group (difference, -3.0% [95% CI, -10.8% to 6.2%]; P = .70). Adverse events occurred in 28/136 (20.6%) participants in the 7-day group vs 33/136 (24.3%) in the 14-day group.
Among afebrile men with suspected UTI, treatment with ciprofloxacin or trimethoprim/sulfamethoxazole for 7 days was noninferior to 14 days of treatment with regard to resolution of UTI symptoms by 14 days after antibiotic therapy. The findings support the use of a 7-day course of ciprofloxacin or trimethoprim/sulfamethoxazole as an alternative to a 14-day course for treatment of afebrile men with UTI.
ClinicalTrials.gov identifier: NCT01994538.
重要性：确定常见传染病的最佳治疗持续时间是保护抗生素有效性的重要策略。
目的：确定在使用环丙沙星或复方磺胺甲噁唑治疗无发热男性下尿路感染（UTI）时，治疗 7 天是否与 14 天一样有效。
设计、地点和参与者：这是一项在 2 家美国退伍军人事务医疗中心进行的无发热男性拟诊症状性 UTI 患者使用环丙沙星或复方磺胺甲噁唑治疗的随机、双盲、安慰剂对照非劣效性试验（招募期：2014 年 4 月至 2019 年 12 月；最终随访期：2020 年 1 月 28 日）。共有 1058 名符合条件的男性，其中 272 名被随机分组。
干预措施：参与者继续接受其治疗医生开的抗生素治疗 7 天，并随机接受继续抗生素治疗（n=136）或安慰剂（n=136）治疗 8 至 14 天。
主要结果和措施：预先指定的主要结局是在完成主动抗生素治疗后 14 天内 UTI 症状的缓解。选择了 10%的非劣效性边界。主要分析采用了接受治疗的人群（接受≥28 剂中的 26 剂且不超过连续 2 剂的参与者），次要分析包括所有按随机分组的患者，无论治疗依从性如何。次要结局包括停药后 28 天内 UTI 症状和/或不良事件的复发。
结果：在 272 名随机分组的患者（中位数[四分位间距]年龄，69[62-73]岁）中，100%完成了试验，254 名（93.4%）患者纳入主要按接受治疗的分析。在 7 天组中，131 名参与者中有 122 名（93.1%）症状缓解，14 天组中 123 名（90.2%）症状缓解（差异，2.9%[1 侧 97.5%置信区间，-5.2%至 ∞]），符合非劣效性标准。在次要的按随机分组分析中，在 7 天组中，136 名参与者中有 125 名（91.9%）症状缓解，在 14 天组中，136 名参与者中有 123 名（90.4%）症状缓解（差异，1.5%[1 侧 97.5%置信区间，-5.8%至 ∞]）。在 7 天组中，131 名参与者中有 13 名（9.9%）症状复发，在 14 天组中，123 名参与者中有 15 名（12.9%）症状复发（差异，-3.0%[95%置信区间，-10.8%至 6.2%]；P=0.70）。在 7 天组中，136 名参与者中有 28 名（20.6%）发生不良事件，在 14 天组中，136 名参与者中有 33 名（24.3%）发生不良事件。
结论和相关性：在无发热的男性疑似 UTI 患者中，与使用 14 天抗生素治疗相比，使用环丙沙星或复方磺胺甲噁唑治疗 7 天在治疗后 14 天内缓解 UTI 症状方面无劣效性。研究结果支持使用 7 天疗程的环丙沙星或复方磺胺甲噁唑作为替代 14 天疗程治疗无发热男性 UTI 的方法。
试验注册：ClinicalTrials.gov 标识符：NCT01994538。
