Puttagunta Sailaja, Aronin Steven I, Gupta Jayanti, Das Anita F, Gupta Kalpana, Dunne Michael W
Consultant, Iterum Therapeutics, Old Saybrook, CT.
Iterum Therapeutics, Old Saybrook, CT.
NEJM Evid. 2025 Jul;4(7):EVIDoa2400414. doi: 10.1056/EVIDoa2400414. Epub 2025 Jun 24.
Existing antibiotics for uncomplicated urinary tract infections are becoming less reliably effective owing to increasing antimicrobial resistance. Our objective was to evaluate the safety and efficacy of sulopenem/probenecid for uncomplicated urinary tract infections.
We conducted a double-blind, randomized, controlled, noninferiority trial of 5 days of sulopenem versus amoxicillin/clavulanate for women with uncomplicated urinary tract infection. The primary end point was overall success, defined as combined clinical cure and microbiologic eradication by day 12, evaluated in the microbiologic-modified intent-to-treat population, which comprised all randomly assigned patients who received any trial medication and had a positive urine culture with 10 colony-forming units (CFU)/ml or more of an Enterobacterales uropathogen (e.g., , species).
A total of 2222 patients were enrolled, and the median age was 51 years (interquartile range, 35-62 years). Ninety-one (9.2%) patients in the primary population (microbiologic-modified intent-to-treat population), the combined population of patients with a positive baseline urine culture and without regard to amoxicillin/clavulanate susceptibility, had a baseline pathogen resistant to three or more classes of antibiotics. Overall success in the microbiologic-modified intent-to-treat population occurred in 318 of 522 (60.9%) participants treated with sulopenem versus 260 of 468 (55.6%) participants treated with amoxicillin/clavulanate (difference, 5.4 percentage points; 95% confidence interval [CI], -0.8 to 11.5), meeting criteria for noninferiority. In the primary population with a baseline uropathogen susceptible to amoxicillin/clavulanate, success occurred in 296 of 480 (61.7%) participants treated with sulopenem versus 243 of 442 (55.0%) participants treated with amoxicillin/clavulanate (difference, 6.7 percentage points; 95% CI, 0.3 to 13.0). In the primary population with a baseline uropathogen not susceptible to amoxicillin/clavulanate, success occurred in 22 of 42 (52.4%) patients treated with sulopenem versus 17 of 25 (68.0%) patients treated with amoxicillin/clavulanate (difference, -15.6 percentage points; 95% CI, -37.5 to 9.1]. Treatment-emergent adverse events occurred more frequently with sulopenem compared with amoxicillin/clavulanate, including diarrhea (8.1% vs. 4.1%), nausea (4.3% vs. 2.9%), and headache (2.2% vs. 1.5%).
Sulopenem was noninferior to amoxicillin/clavulanate for the treatment of adult women with uncomplicated urinary tract infection, but was associated with more frequent mild adverse events. (Funded by Iterum Therapeutics; REASSURE ClinicalTrials.gov number, NCT05584657.).
由于抗菌药物耐药性增加，现有的用于治疗单纯性尿路感染的抗生素疗效越来越不可靠。我们的目的是评估舒洛培南/丙磺舒治疗单纯性尿路感染的安全性和有效性。
我们进行了一项双盲、随机、对照、非劣效性试验，比较舒洛培南与阿莫西林/克拉维酸治疗单纯性尿路感染女性患者5天的疗效。主要终点是总体成功率，定义为到第12天临床治愈和微生物清除的综合情况，在微生物学改良意向性治疗人群中进行评估，该人群包括所有随机分配并接受任何试验药物治疗且尿培养阳性（每毫升有10个菌落形成单位（CFU）或更多肠杆菌科尿路致病菌（如 种））的患者。
共纳入2222例患者，中位年龄为51岁（四分位间距为35 - 62岁）。在主要人群（微生物学改良意向性治疗人群）中，即基线尿培养阳性且不考虑阿莫西林/克拉维酸敏感性的患者群体中，91例（9.2%）患者的基线病原体对三类或更多类抗生素耐药。微生物学改良意向性治疗人群中，接受舒洛培南治疗的522例参与者中有318例（60.9%）总体成功，接受阿莫西林/克拉维酸治疗的468例参与者中有260例（55.6%）总体成功（差异为5.4个百分点；95%置信区间[CI]，-0.8至11.5），符合非劣效性标准。在基线尿路致病菌对阿莫西林/克拉维酸敏感的主要人群中，接受舒洛培南治疗的480例参与者中有296例（61.7%）成功，接受阿莫西林/克拉维酸治疗的442例参与者中有243例（55.0%）成功（差异为6.7个百分点；95%CI，0.3至13.0）。在基线尿路致病菌对阿莫西林/克拉维酸不敏感的主要人群中，接受舒洛培南治疗的42例患者中有22例（52.4%）成功，接受阿莫西林/克拉维酸治疗的25例患者中有17例（68.0%）成功（差异为-15.6个百分点；95%CI，-37.5至9.1）。与阿莫西林/克拉维酸相比，舒洛培南治疗后出现的不良事件更频繁，包括腹泻（8.1%对4.1%）、恶心（4.3%对2.9%）和头痛（2.2%对1.5%）。
舒洛培南在治疗成年女性单纯性尿路感染方面不劣于阿莫西林/克拉维酸，但与更频繁的轻度不良事件相关。（由Iterum Therapeutics资助；REASSURE临床试验注册号，NCT05584657。）
