At ESCMID Global 2025, antimicrobial resistance stood out as one of the most pressing topics. As carbapenem resistance rises to alarming levels worldwide, the medical community is urgently seeking viable alternatives. Surprisingly, some older antibiotics, like Temocillin, are gaining renewed attention due to their favorable properties and ability to spare broader-spectrum agents. Temocillin, originally introduced in the 1980s, has re-emerged as a narrow-spectrum β-lactam with promising activity against multidrug-resistant Enterobacterales. Infectious Disease Frontier(IDF) spoke with Dr. Francesco Cogliati Dezza to discuss the growing importance of Temocillin in the treatment of ESBL-producing pathogens, the findings of the ASTARTÉ trial, and how this agent might support carbapenem-sparing strategies in modern clinical practice.IDF: The issue of carbapenem resistance is becoming increasingly severe, while drugs like Temocillin seem to be overlooked. What do you think is the significance of seeking carbapenem alternative solutions? What are some potential alternatives currently available?
Dr. Francesco Cogliati Dezza: Hi everyone, thanks for this interview. This is a very important question. We know that carbapenem resistance is a huge problem. To treat infections caused by carbapenem-resistant organisms, we now have a range of options like β-lactam/β-lactamase inhibitors—for example, ceftazidime-avibactam and other new drugs. Each of these agents has its specific place in therapy.
But when we think about why we now face widespread carbapenem resistance, we need to look back over the past 20 years and consider how much carbapenem, especially meropenem, has been used globally. We need to shift focus, especially toward gram-negative organisms and ESBL- or AmpC-producing enterobacterales.
Temocillin, in this context, is making a comeback. Although it was originally marketed in the 1980s, it’s gaining renewed interest now because it has a narrow spectrum it’s only active against enterobacterales and it is stable against hydrolysis by ESBLs, AmpC. So, it seems to be a very advantageous drug in infections involving these resistance mechanisms. Which drugs today resemble Temocillin? For multidrug-resistant infections that are not carbapenem-resistant, we sometimes use piperacillin-tazobactam, but the data in literature are controversial whether piperacillin-tazobactam is inferior or equivalent to carbapenems is still debated, as shown in the MERINO trial. We also consider amoxicillin-clavulanate if the ESBL-producing bacteria are susceptible, but both piperacillin-tazobactam and amoxicillin-clavulanate are often used for other infections by different gram-negative microorganism or anaerobic as well.
So, thinking about which drugs we need and what we currently have Temocillin is unique. There’s really nothing quite like it right now. It’s specifically useful against enterobacterales that produce ESBL or AmpC enzymes, and with this very narrow spectrum and low ecological impact, Temocillin is a very good therapeutic option.
IDF: Could you share with us the ASTARTÉ study you reported, which showed the efficacy and safety profile of Temocillin for targeted treatment of 3GCR-E (third-generation cephalosporin-resistant Enterobacteriaceae) bacteremia?
Dr. Francesco Cogliati Dezza: Of course. My comments on the first question were based on the preliminary results of the ASTARTÉ study. This was a non-inferiority trial comparing Temocillin with meropenem. The trial was coordinated by the Infectious Diseases and Microbiology Clinical Unit, University Hospital Virgen Macarena in Seville Spain and funded by National Health Institute Carlos III. We used a composite outcome of clinical success, composed by (a) clinical cure at test-of-cure (7–10 days after end of treatment); (b) no need to stop or change study drug because of adverse event or failure; (c) no recurrence of bacteraemia until day 28; (d) alive at day 28. These four variables were combined into one “clinical success” endpoint to evaluate the impact of Temocillin versus meropenem.
The result was that there was no difference between the two arms—71.5% of patients in both groups achieved clinical success. The absolute difference was zero, and the non-inferiority margin of 10% was not crossed. That’s the main conclusion of this trial.
What’s also interesting is that this low difference between Temocillin and meropenem was also seen in various subgroups. Of course, the non-inferiority margin doesn’t formally apply to subgroup analyses, but still, the difference was very low. Based on these preliminary results, we believe Temocillin has a place in therapy. We could comfortably use it for E. coli bacteremia originating from the urinary tract, regardless of disease severity whether there’s sepsis, no sepsis, or even septic shock. However, looking at our data, we would be more cautious when using Temocillin in certain subgroups, such as immunocompromised patients, other Enterobacterales species, or cases where the source control is no urinary mainly because of the small number of patients in those categories. Overall, the preliminary data are very encouraging. We are now waiting for the final results and hope to publish them soon to share our experience with clinicians around the world.
IDF: In this study, the 3GCR-E primarily originated from urinary tract infections. Does Temocillin also have similar efficacy and safety in other types of 3GCR-E infections, including abdominal, respiratory, and CNS infections?
Dr. Francesco Cogliati Dezza: Yes, that’s an important point. Most of the infections in our trial came from the urinary tract. Regarding other sources—like intra-abdominal, biliary tract, and others—we had a limited number of cases, so unfortunately, we couldn’t draw strong conclusions or recommendations for Temocillin in those situations. We also had limited representation of other Enterobacterales species. Around 20% of isolates were Klebsiella pneumoniae, and the remaining 80% were other types of bacteria. Again, the small numbers make it difficult to make definitive claims.That said, we do know that Temocillin has the pharmacokinetic and pharmacodynamic properties to reach various infection sites—it can penetrate the CNS, lungs, and intra-abdominal areas. So, it theoretically has the capacity to treat infections in different body compartments. Still, because Temocillin achieves especially high concentrations in the urinary tract, we currently see that as its ideal target area. Also, urinary tract infections are among the most common sources of Enterobacterales bacteremia, so this makes Temocillin a strong candidate for these cases. In the future, with more data, we may be able to expand its use. For now, we believe Temocillin is a valuable agent to support carbapenem-sparing strategies in urinary tract-associated bloodstream infections.
Temocillin is re-emerging as a valuable antimicrobial agent in the fight against multidrug-resistant Enterobacterales, particularly in the context of urinary tract infections caused by ESBL- and AmpC-producing organisms. As shown in the ASTARTÉ trial, it demonstrated non-inferiority to meropenem, offering a viable alternative in targeted treatment settings.
While more research is needed to define its role in other infection types, Temocillin’s pharmacological properties and narrow spectrum make it a strong candidate for stewardship programs aimed at reducing carbapenem overuse. As resistance threats evolve, drugs like Temocillin may find renewed purpose—not just as relics from the past, but as strategic tools for the future.
Infectious and Tropical Diseases Specialist
Infectious Diseases and Microbiology Clinical Unit, University Hospital Virgen Macarena
Department of Medicine, University of Seville, Biomedicine Institute of Sevilla (IBiS) Seville, Spain
Department of Public Health and Infectious Diseases, Sapienza University of Rome
Trial fundig: This study was funded by Instituto de Salud Carlos III. Call for proposal “Proyectos de Investigación Clínica Independiente de la Acción Estratégica en Salud 2019”, grant agreement No ICI19/00093.
