TOPLINE

Temocillin demonstrated non-inferior efficacy compared with carbapenems for the targeted treatment of bacteraemia caused by third-generation cephalosporin-resistant Enterobacterales. The occurrence of adverse events (AEs) and serious AEs also did not differ significantly between the temocillin and carbapenem groups; however, numerically more AEs occurred with temocillin.

METHODOLOGY

• Researchers conducted a phase 3, open-label, non-inferiority trial to investigate whether temocillin was non-inferior to carbapenems for the targeted treatment of bacteraemia caused by third-generation cephalosporin-resistant Enterobacterales.
• They enrolled eligible patients from 29 Spanish hospitals between December 15, 2020, and November 29, 2024; eligible patients had monomicrobial bloodstream infection caused by Enterobacterales resistant to cefotaxime, ceftriaxone, or ceftazidime and susceptible to meropenem and temocillin and required at least 4 days of active intravenous therapy.
• Patients received at least one dose of either 2 g temocillin (n = 163) every 8 hours as a 30-40-minute infusion or 1 g meropenem (n = 165) every 8 hours as a 15-30-minute infusion (or 1 g ertapenem once daily, if deemed appropriate).
• The primary endpoint was clinical success, defined as resolution of all new signs and symptoms related to the infection at the test of cure, no need to stop or change the study drug because of an AE or clinical failure, no recurrence until day 28, and survival at day 28. The non-inferiority margin was set at 10%.
• Secondary endpoints included the individual components of the primary endpoint, reinfections until day 28, microbiologic cure, and mortality and AEs at day 28.

TAKEAWAY

• Clinical success occurred in 74% of patients in the temocillin group and 73% of patients in the carbapenem group. The absolute difference was 0.3 percentage points (one-sided 95% CI, -7.7 to ∞; P = .017), demonstrating the non-inferiority of temocillin.
• Secondary endpoints were consistent with the non-inferiority findings. The 28-day mortality rate was 2% in the temocillin group vs 4% in the carbapenem group (difference, -1.2; 95% CI, -∞ to 1.9), and clinical cure rates were 80% and 82% in the temocillin and carbapenem groups, respectively (difference, -2.0; 95% CI, -9.2 to ∞).
• Overall, the number of AEs did not differ significantly between the groups, and AEs were reported in 60% of those on temocillin and 41% of those on carbapenems, whereas serious AEs occurred in 19% of those on temocillin vs 24% of those on carbapenems.
• The probability that patients in the temocillin group had a better desirability of outcome ranking than those in the carbapenem group was 50.4%, indicating comparable outcomes between the groups.

IN PRACTICE

"…the ASTARTÉ trial provides practice-changing evidence that alternative agents other than carbapenems can be used for the treatment of bacteraemia caused by third-generation cephalosporin-resistant Enterobacterales," wrote the authors of a linked commentary.

SOURCE

The study was led by Francesco Cogliati Dezza, MD, Hospital Universitario Virgen Macarena and Departamento de Medicina, Universidad de Sevilla, Instituto de Biomedicina de Sevilla in Seville, Spain. It was published online on July 9, 2026, in The Lancet.

LIMITATIONS 

The study could not be masked because the control groups included two optional drugs with different dosing schemes. The overall median duration of therapy was slightly longer than that supported by recent evidence for bacteraemia management. The study was performed in only one country, with most patients being of Western Europe ethnicity.

DISCLOSURES

This study received funding from Instituto de Salud Carlos III. Temocillin was supplied by Eumedica Pharmaceuticals in Switzerland through its partner company, Belpharma, in Luxembourg. Several authors disclosed receiving various types of financial support from pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.