ArticleAntimicrobial agents and chemotherapy2009
In vitro activity of LK-157, a novel tricyclic carbapenem as broad-spectrum {beta}-lactamase inhibitor.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 41 citations in OpenAlex.
- Characterization of GQA as a novel β-lactamase inhibitor of CTX-M-15 and KPC-2 enzymes.Microbial cell factories · 2024Article
- Tackling the outer membrane: facilitating compound entry into Gram-negative bacterial pathogens.npj antimicrobials and resistance · 2023Review
- Population pharmacokinetics of piperacillin in febrile children receiving cancer chemotherapy: the impact of body weight and target on an optimal dosing regimen.The Journal of antimicrobial chemotherapy · 2019Article
- Resensitization of methicillin-resistantHeliyon · 2018Article
- A structural, epidemiological & genetic overview ofThe Indian journal of medical research · 2016Review
- Kinetics of the Interaction between BAL29880 and LK157 and the Class C β-Lactamase CHE-1.Antimicrobial agents and chemotherapy · 2016Article
- Novel β-lactamase inhibitors: a therapeutic hope against the scourge of multidrug resistance.Frontiers in microbiology · 2013Article
- Overcoming resistance to β-lactam antibiotics.The Journal of organic chemistry · 2013Review
- Combination approaches to combat multidrug-resistant bacteria.Trends in biotechnology · 2013Review
- Raman spectra of interchanging β-lactamase inhibitor intermediates on the millisecond time scale.Journal of the American Chemical Society · 2013Article
- Carbapenems: past, present, and future.Antimicrobial agents and chemotherapy · 2011Review
- Review
- Three decades of beta-lactamase inhibitors.Clinical microbiology reviews · 2010Review
- In vitro activity of LK-157, a novel tricyclic carbapenem as broad-spectrum {beta}-lactamase inhibitor.Antimicrobial agents and chemotherapy · 2009Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
LK-157 is a novel tricyclic carbapenem with potent activity against class A and class C beta-lactamases. When tested against the purified TEM-1 and SHV-1 enzymes, LK-157 exhibited 50% inhibitory concentrations (IC(50)s) in the ranges of the clavulanic acid and tazobactam IC(50)s (55 nM and 151 nM, respectively). Moreover, LK-157 significantly inhibited AmpC beta-lactamase (IC(50), 62 nM), as LK-157 was >2,000-fold more potent than clavulanic acid and approximately 28-fold more active than tazobactam. The in vitro activities of LK-157 in combination with amoxicillin, piperacillin, ceftazidime, cefotaxime, ceftriaxone, cefepime, cefpirome, and aztreonam against an array of Ambler class A (TEM-, SHV-, CTX-M-, KPC-, PER-, BRO-, and PC-type)- and class C-producing bacterial strains derived from clinical settings were evaluated in synergism experiments and compared with those of clavulanic acid, tazobactam, and sulbactam. In vitro MICs against ESBL-producing strains (except CTX-M-containing strains) were reduced 2- to >256-fold, and those against AmpC-producing strains were reduced even up to >32-fold. The lowest MICs (< or =0.025 to 1.6 microg/ml) were observed for the combination of cefepime and cefpirome with a constant LK-157 concentration of 4 microg/ml, thus raising an interest for further development. LK-157 proved to be a potent beta-lactamase inhibitor, combining activity against class A and class C beta-lactamases, which is an absolute necessity for use in the clinical setting due to the worldwide increasing prevalence of bacterial strains resistant to beta-lactam antibiotics.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.