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

July 9, 2026| Source: Lancet (London, England)

Alternatives to carbapenems for the treatment of third-generation cephalosporin-resistant Enterobacterales (3GCR-E) are urgently needed to reduce the selection pressure posed by these drugs. Temocillin is a neglected narrow-spectrum β-lactam. 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. This multicentre, phase 3, open-label, non-inferiority, randomised, pragmatic, investigator-initiated clinical trial was conducted in 29 Spanish hospitals. 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). 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. Randomisation (1:1) was stratified according to previous active drug and to source of infection; no blocks were used. The primary endpoint was clinical success (clinical cure, no need to stop or change the study drug because of adverse event or 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-treat population [mITT]). Adverse events were assessed in the mITT population. No missing data were reported. A 10% non-inferiority margin was established. The trial was registered in ClinicalTrials.gov (NCT04478721) and is complete and closed to new participants. 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). 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). 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). Serious adverse events were reported in 31 (19%) of 163 patients assigned temocillin and 35 (24%) of 165 patients assigned carbapenems. In patients with bacteraemia caused by 3GCR-E, temocillin was non-inferior to carbapenems as targeted treatment. These findings support the use of temocillin as an effective and safe alternative to carbapenems in this setting. Instituto de Salud Carlos III.

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Temocillin versus carbapenems for bacteraemia due to third-generation cephalosporin-resistant Enterobacterales in Spain (ASTART&#xc9;): a multicentre, phase 3, open-label, non-inferiority, randomised