本文由小咖机器人翻译整理

期刊来源：N Engl J Med

原文链接：https://doi.org/10.1056/NEJMoa2304748

摘要内容如下：

背景

耐碳青霉烯类肠杆菌和多重耐药铜绿假单胞菌是全球性的健康威胁。头孢吡肟-塔尼波巴坦是一种正在研究的β-内酰胺和β-内酰胺酶抑制剂组合，具有抗肠杆菌属和铜绿假单胞菌表达丝氨酸和金属β-内酰胺酶的活性。

方法

在这项3期、双盲、随机试验中，我们将患有复杂性尿路感染（UTI）（包括急性肾盂肾炎）的住院成人以2:1的比例分配接受静脉注射头孢吡肟-塔尼波巴坦（2.5 G）或美罗培南（1 G），每8小时一次，共7天。在菌血症的情况下，该持续时间可延长至14天。在微生物学意向治疗（MICROITT）人群（具有合格的革兰氏阴性病原体的患者，两种研究药物对其均有效）中，主要结果是试验第19至23天的微生物学和临床成功（复合成功）。在确认非劣效性后，对主要结果进行预先指定的优势分析。

结果

在接受随机分组的661例患者中，436例（66.0%）被纳入MicroITT人群。患者的平均年龄为56.2岁，其中38.1%为65岁或以上。在MicroITT人群中，57.8%的患者患有复杂性泌尿道感染，42.2%患有急性肾盂肾炎，13.1%患有菌血症。头孢吡肟-塔尼巴坦组293例患者中有207例（70.6%）复合成功，美罗培南组143例患者中有83例（58.0%）复合成功。就主要转归而言，头孢吡肟-塔尼波巴坦优于美罗培南（治疗差异，12.6个百分点；95%置信区间，3.1至22.2；P=0.009）。治疗反应的差异在随访后期（试验第28至35天）持续存在，此时头孢吡肟-塔尼巴坦具有更高的复合成功率和临床成功率。头孢吡肟-塔尼波巴坦组和美罗培南组的不良事件发生率分别为35.5%和29.0%，其中头痛、腹泻、便秘、高血压和恶心的发生率最高。两组发生严重不良事件的频率相似。

结论

在治疗包括急性肾盂肾炎在内的复杂性泌尿道感染方面，头孢吡肟-塔尼波巴坦优于美罗培南，其安全性与美罗培南相似。（由Venatorx制药公司和其他公司资助；Certain-1 ClinicalTrials.gov编号，NCT03840148。）

英文原文如下：

Abstracts

BACKGROUND  Carbapenem-resistant Enterobacterales species and multidrug-resistant Pseudomonas aeruginosa are global health threats. Cefepime-taniborbactam is an investigational β-lactam and β-lactamase inhibitor combination with activity against Enterobacterales species and P. aeruginosa expressing serine and metallo-β-lactamases.

METHODS  In this phase 3, double-blind, randomized trial, we assigned hospitalized adults with complicated urinary tract infection (UTI), including acute pyelonephritis, in a 2:1 ratio to receive intravenous cefepime-taniborbactam (2.5 g) or meropenem (1 g) every 8 hours for 7 days; this duration could be extended up to 14 days in case of bacteremia. The primary outcome was both microbiologic and clinical success (composite success) on trial days 19 to 23 in the microbiologic intention-to-treat (microITT) population (patients who had a qualifying gram-negative pathogen against which both study drugs were active). A prespecified superiority analysis of the primary outcome was performed after confirmation of noninferiority.

RESULTS  Of the 661 patients who underwent randomization, 436 (66.0%) were included in the microITT population. The mean age of the patients was 56.2 years, and 38.1% were 65 years of age or older. In the microITT population, 57.8% of the patients had complicated UTI, 42.2% had acute pyelonephritis, and 13.1% had bacteremia. Composite success occurred in 207 of 293 patients (70.6%) in the cefepime-taniborbactam group and in 83 of 143 patients (58.0%) in the meropenem group. Cefepime-taniborbactam was superior to meropenem regarding the primary outcome (treatment difference, 12.6 percentage points; 95% confidence interval, 3.1 to 22.2; P = 0.009). Differences in treatment response were sustained at late follow-up (trial days 28 to 35), when cefepime-taniborbactam had higher composite success and clinical success. Adverse events occurred in 35.5% and 29.0% of patients in the cefepime-taniborbactam group and the meropenem group, respectively, with headache, diarrhea, constipation, hypertension, and nausea the most frequently reported; the frequency of serious adverse events was similar in the two groups.

CONCLUSIONS  Cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a safety profile similar to that of meropenem. (Funded by Venatorx Pharmaceuticals and others; CERTAIN-1 ClinicalTrials.gov number, NCT03840148.).

-----------分割线---------

点击链接：https://www.mediecogroup.com/community/user/vip/categories/ ，成为医咖会员，获取12项专属权益。

现在购买可享受最大优惠（买一年送三个月，买两年送一年），2024年2月10日起将不再享有该优惠。