Temocillin versus meropenem for the targeted treatment of bacteraemia due to third-generation cephalosporin-resistant<i>Enterobacterales</i>(ASTARTÉ): protocol for a randomised, pragmatic trial

The emergence of carbapenem-resistant organisms (CROs) is a significant global threat. Reduction of carbapenem consumption can decrease CROs. In the global endemic era of ESBL-producing bacteria, carbapenems are considered the treatment of choice, leading to challenge in limiting carbapenem use. This review describes the role of precision prescribing for prevention of CROs. This involves improving antibiotic selection, dosing and shortening duration. The effect of different antibiotics, dosing and duration on CRO development are explored. Available options for precision prescribing, gaps in the scientific evidence, and areas for future research are also presented.

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“… 112 Currently, there is an ongoing clinical trial evaluating the efficacy of temocillin for ESBL-E bacteraemia. 113 …”

Section: Carbapenem-sparing Options For the Treatment Of Esbl-ementioning

confidence: 99%

Can precision antibiotic prescribing help prevent the spread of carbapenem-resistant organisms in the hospital setting?

Vasikasin

Rawson

Holmes

et al. 2023

JAC-Antimicrobial Resistance

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“…This suggests that temocillin may be a potential treatment for ESBL and AmpC producing UPEC causing UTI. A phase 3 clinical trial is currently recruiting to compare the efficacy of temocillin versus meropenem against third-generation cephalosporin resistant Enterobacterales [ 86 ].…”

Section: Current Treatment Options For Mdr Upecmentioning

confidence: 99%

Current and Emerging Treatment Options for Multidrug Resistant Escherichia coli Urosepsis: A Review

Walker

Roberts²,

Rogers³

et al. 2022

Antibiotics

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Escherichia coli is a versatile commensal and pathogenic member of the human microflora. As the primary causative pathogen in urosepsis, E. coli places an immense burden on healthcare systems worldwide. To further exacerbate the issue, multi drug resistance (MDR) has spread rapidly through E. coli populations, making infections more troublesome and costlier to treat. This paper aimed to review the literature concerning the development of MDR in uropathogenic E. coli (UPEC) and explore the existing evidence of current and emerging treatment strategies. While some MDR strains maybe treated with β-lactam-β-lactamase inhibitor combinations as well as cephalosporins, cephamycin, temocillin and fosfomycin, current treatment strategies for many MDR UPEC strains are reliant on carbapenems. Carbapenem overreliance may contribute to the alarming dissemination of carbapenem-resistance amongst some UPEC communities, which has ushered in a new age of difficult to treat infections. Alternative treatment options for carbapenem resistant UPEC may include novel β-lactam-β-lactamase or carbapenemase inhibitor combinations, cefiderocol, polymyxins, tigecycline, aminoglycosides or fosfomycin. For metallo-β-lactamase producing strains (e.g., NDM, IMP-4), combinations of cefazidime-avibacam with aztreonam have been used. Additionally, the emergence of new antimicrobials brings new hope to the treatment of such infections. However, continued research is required to successfully bring these into the clinic for the treatment of MDR E. coli urosepsis.

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“…Temocillin exhibits unusual stability against extended-spectrum beta-lactamases (ESBL), AmpC and KPC enzymes [8], raising interest in drug repurposing. Indeed, at present, there are two ongoing clinical trials, whose aim is the comparison between temocillin and carbapenems in complicated UTI [9] and BSI [10] due to Gram-negative bacteria resistant to third generation cephalosporins. From an antimicrobial stewardship perspective, the inactivity of temocillin against metallo beta-lactamase and OXA-enzymes may be seen as an advantage, making it a strict anti-KPC agent.…”

Section: Introductionmentioning

confidence: 99%

Synergistic Activity of Temocillin and Fosfomycin Combination against KPC-Producing <em>Klebsiella pneumoniae </em>Clinical Isolates

Costantino,

Principe,

Mehat

et al. 2024

Preprint

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Infections caused by KPC-producing K. pneumoniae continue to pose a significant clinical challenge due to emerging resistance to new antimicrobials. We investigated the association between two drugs whose roles have been repurposed against multidrug-resistant bacteria: fosfomycin and temocillin. Temocillin exhibits unusual stability against KPC enzymes, while fosfomycin acts as a potent “synergizer”. We conducted in vitro antimicrobial activity studies on 100 clinical isolates of KPC-producing K. pneumoniae using a combination of fosfomycin and temocillin. The results demonstrated synergistic activity in 91% of the isolates. Subsequently, we assessed the effect on Galleria mellonella larvae using 5 different KPC-Kp isolates. The addition of fosfomycin to temocillin increased larvae survival from 73 to 97% (+Δ 32%; isolate 1), from 93 to 100% (+Δ 7%; isolate 2), from 63 to 86% (+Δ 36%; isolate 3), from 63 to 90% (+Δ 42%; isolate 4), and from 93 to 97% (+Δ 4%; isolate 10), respectively. Among the temocillin-resistant KPC-producing K. pneumoniae isolates (24 isolates), the addition of fosfomycin reduced temocillin MIC values below the resistance breakpoint in all isolated except one. Temocillin combined with fosfomycin emerges as a promising combination against KPC-producing K. pneumoniae, warranting further clinical evaluation.

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Temocillin versus meropenem for the targeted treatment of bacteraemia due to third-generation cephalosporin-resistantEnterobacterales(ASTARTÉ): protocol for a randomised, pragmatic trial

Cited by 9 publications

References 20 publications

Can precision antibiotic prescribing help prevent the spread of carbapenem-resistant organisms in the hospital setting?

Can precision antibiotic prescribing help prevent the spread of carbapenem-resistant organisms in the hospital setting?

Current and Emerging Treatment Options for Multidrug Resistant Escherichia coli Urosepsis: A Review

Synergistic Activity of Temocillin and Fosfomycin Combination against KPC-Producing <em>Klebsiella pneumoniae </em>Clinical Isolates

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