Ceftibuten-Ledaborbactam Activity against Multidrug-Resistant and Extended-Spectrum-β-Lactamase-Positive Clinical Isolates of
            <i>Enterobacterales</i>
            from a 2018–2020 Global Surveillance Collection

Karlowsky, James A.; Wise, Mark G.; Hackel, Meredith; Pevear, Daniel C.; Moeck, Greg; Sahm, Daniel F.

doi:10.1128/aac.00934-22

Cited by 7 publications

(1 citation statement)

References 13 publications

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“…Ledaborbactam etzadroxil ( 73) is an esterase-cleavable prodrug of the bicyclic boronate-type BLI (new class [333]) of ledaborbactam (75) (VNRX-5236) [358], while 74 is a third-generation cephalosporin first approved in 1995. The ledaborbactam etzadroxil (73) + ceftibuten (74) combination is active against clinicallyderived Enterobacterales that express ESBLs and serine carbapenemases [359][360][361].…”

Section: β-Lactam/β-lactamase Inhibitor (Bl/bli) Combinations Undergo...mentioning

confidence: 99%

Antibiotics in the clinical pipeline as of December 2022

et al. 2023

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The need for new antibacterial drugs to treat the increasing global prevalence of drug-resistant bacterial infections has clearly attracted global attention, with a range of existing and upcoming funding, policy, and legislative initiatives designed to revive antibacterial R&D. It is essential to assess whether these programs are having any real-world impact and this review continues our systematic analyses that began in 2011. Direct-acting antibacterials (47), non-traditional small molecule antibacterials (5), and β-lactam/β-lactamase inhibitor combinations (10) under clinical development as of December 2022 are described, as are the three antibacterial drugs launched since 2020. Encouragingly, the increased number of early-stage clinical candidates observed in the 2019 review increased in 2022, although the number of first-time drug approvals from 2020 to 2022 was disappointingly low. It will be critical to monitor how many Phase-I and -II candidates move into Phase-III and beyond in the next few years. There was also an enhanced presence of novel antibacterial pharmacophores in early-stage trials, and at least 18 of the 26 phase-I candidates were targeted to treat Gram-negative bacteria infections. Despite the promising early-stage antibacterial pipeline, it is essential to maintain funding for antibacterial R&D and to ensure that plans to address late-stage pipeline issues succeed.

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Section: β-Lactam/β-lactamase Inhibitor (Bl/bli) Combinations Undergo...mentioning

confidence: 99%

Antibiotics in the clinical pipeline as of December 2022

et al. 2023

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Evolving resistance landscape in gram‐negative pathogens: An update on β‐lactam and β‐lactam‐inhibitor treatment combinations for carbapenem‐resistant organisms

Koenig,

Kuti

2024

Pharmacotherapy

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Antibiotic resistance has become a global threat as it is continuously growing due to the evolution of β‐lactamases diminishing the activity of classic β‐lactam (BL) antibiotics. Recent antibiotic discovery and development efforts have led to the availability of β‐lactamase inhibitors (BLIs) with activity against extended‐spectrum β‐lactamases as well as Klebsiella pneumoniae carbapenemase (KPC)‐producing carbapenem‐resistant organisms (CRO). Nevertheless, there is still a lack of drugs that target metallo‐β‐lactamases (MBL), which hydrolyze carbapenems efficiently, and oxacillinases (OXA) often present in carbapenem‐resistant Acinetobacter baumannii. This review aims to provide a snapshot of microbiology, pharmacology, and clinical data for currently available BL/BLI treatment options as well as agents in late stage development for CRO harboring various β‐lactamases including MBL and OXA‐enzymes.

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