Temocillin versus carbapenems for bacteraemia due to third-generation cephalosporin-resistant Enterobacterales in Spain (ASTARTÉ): a multicentre, phase 3, open-label, non-inferiority, randomised clinical trial.

Temocillin is a neglected narrow-spectrum β-lactam.

特莫西林是一种被忽视的窄谱β-内酰胺类抗生素。

The aim of the trial was to investigate if temocillin is non-inferior to carbapenems for the targeted treatment of bacteraemia due to 3GCR-E.

该试验旨在研究temocillin对于治疗由3GCR-E引起的菌血症是否不劣于碳青霉烯类药物。

Methods

This multicentre, phase 3, open-label, non-inferiority, randomised, pragmatic, investigator-initiated clinical trial was conducted in 29 Spanish hospitals.

这是一项多中心、第三阶段、开放标签、非劣效性、随机、实用性的研究者发起的临床试验，在29家西班牙医院进行。

We randomly assigned patients with bacteraemia caused by 3GCR-E to receive intravenous temocillin (2 g every 8 h) or meropenem (1 g every 8 h; or ertapenem [1 g per day] if appropriate).

我们随机分配了由3GCR-E引起的菌血症患者，接受静脉注射temocillin（每8小时2克）或meropenem（每8小时1克；如果适当，也可以使用ertapenem[每天1克]）治疗。

Patients aged 18 years or older were eligible if they had monomicrobial bacteraemia due to any 3GCR-E that was susceptible to meropenem and temocillin and treatment for at least 4 days with an active intravenous drug was considered necessary.

如果患者年龄在18岁或以上，并且由于对meropenem和temocillin敏感的任何3GCR-E引起的单微生物菌血症，并且认为至少需要4天的活性静脉药物治疗，则符合入选条件。

Randomisation (1:1) was stratified according to previous active drug and to source of infection; no blocks were used.

随机化（1:1）根据先前使用的活性药物和感染来源进行了分层；未使用分组。

The primary endpoint was clinical success (clinical cure, no need to stop or change the study drug because of adverse eventor clinical failure, absence of recurrence, and survival by day 28) in all randomly assigned patients who received at least one dose of a study drug (modified intention-to-treatpopulation [mITT]).

主要终点是临床成功（临床治愈，无需因不良事件或临床失败而停止或更改研究药物，无复发，以及第28天的生存率）在所有接受至少一次研究药物治疗的随机分配患者中（修改意向治疗人群[mITT]）。

Adverse events were assessed in the mITT population.

在修正意向性治疗(mITT)人群中评估了不良事件。

No missing data were reported.

未报告有缺失数据。

A 10% non-inferiority margin was established.

确立了10%的非劣效性边界。

The trial was registered in ClinicalTrials.gov (NCT04478721) and is complete and closed to new participants.

该试验已在ClinicalTrials.gov注册（NCT04478721），目前已完成并停止接受新参与者。

Results

334 eligible patients were enrolled between Dec 15, 2020, and Nov 29, 2024, of whom 328 were included in the mITT population (163 assigned temocillin and 165 assigned carbapenems).

在2020年12月15日至2024年11月29日期间，共有334名符合条件的患者被纳入研究，其中328名被纳入改良意向治疗(mITT)人群（163名被分配到temocillin组，165名被分配到碳青霉烯类抗生素组）。

In 328 participants, the median age was 72 years (IQR 65-80), 106 (32%) were female, 222 (68%) were male, and the median Charlson Comorbidity Index was 2 (IQR 0-4).

在328名参与者中，中位年龄为72岁（四分位数间距65-80岁），女性106名（占32%），男性222名（占68%），中位Charlson合并症指数为2（四分位数间距0-4）。

In the mITT population, clinical success occurred in 120 (74%) of 163 patients assigned temocillin and 121 (73%) of 165 patients assigned carbapenems (difference 0·3% [95% CI -7·7 to ∞]; non-inferiority p=0·017).

在mITT人群中，163名被分配temocillin的患者中有120名（74%）和165名被分配碳青霉烯类的患者中有121名（73%）实现了临床成功（差异0.3% [95% 置信区间-7.7至∞]；非劣效性p=0.017）。

Serious adverse events were reported in 31 (19%) of 163 patients assigned temocillin and 35 (24%) of 165 patients assigned carbapenems.

在分配到temocillin的163名患者中，有31名（19%）报告了严重不良事件，在分配到碳青霉烯类的165名患者中，有35名（24%）报告了严重不良事件。

interpretation

In patients with bacteraemia caused by 3GCR-E, temocillin was non-inferior to carbapenems as targeted treatment.

在由3GCR-E引起的菌血症患者中，temocillin作为靶向治疗与碳青霉烯类抗生素相比具有非劣性。

These findings support the use of temocillin as an effective and safe alternative to carbapenems in this setting.

这些发现支持在这一背景下，将temocillin作为碳青霉烯类抗生素的有效且安全的替代品使用。

funding

Instituto de Salud Carlos III.

卡洛斯三世健康研究所