ArticleAntimicrobial agents and chemotherapy2004
In vitro and in vivo activities of novel 6-methylidene penems as beta-lactamase inhibitors.
Article in Antimicrobial agents and chemotherapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 54 citations in OpenAlex.
- Targeting mycobacterial transpeptidases: evaluating the roles of Ldt and PBP inhibition in suppressingAntimicrobial agents and chemotherapy · 2025Article
- Antibiotic tolerance and persistence in clinical isolates ofMicrobiology spectrum · 2025Article
- β-Lactam Antibiotics and β-Lactamase Enzymes Inhibitors, Part 2: Our Limited Resources.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Recommendations to Synthetize Old and New β-Lactamases Inhibitors: A Review to Encourage Further Production.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Discovery of VNRX-7145 (VNRX-5236 Etzadroxil): An Orally Bioavailable β-Lactamase Inhibitor for Enterobacterales Expressing Ambler Class A, C, and D Enzymes.Journal of medicinal chemistry · 2021Article
- Microbiological Characterization of VNRX-5236, a Broad-Spectrum β-Lactamase Inhibitor for Rescue of the Orally Bioavailable Cephalosporin Ceftibuten as a Carbapenem-Sparing Agent against Strains ofAntimicrobial agents and chemotherapy · 2021Article
- New Carbapenemase Inhibitors: Clearing the Way for the β-Lactams.International journal of molecular sciences · 2020Review
- Activity of the β-Lactamase Inhibitor LN-1-255 against Carbapenem-Hydrolyzing Class D β-Lactamases from Acinetobacter baumannii.Antimicrobial agents and chemotherapy · 2017Article
- Kinetic and Structural Characterization of the Interaction of 6-Methylidene Penem 2 with the β-Lactamase from Mycobacterium tuberculosis.Biochemistry · 2015Article
- Bactericidal activity, absence of serum effect, and time-kill kinetics of ceftazidime-avibactam against β-lactamase-producing Enterobacteriaceae and Pseudomonas aeruginosa.Antimicrobial agents and chemotherapy · 2014Article
- Article
- New treatment options against gram-negative organisms.Critical care (London, England) · 2011Review
- Review
- In vitro activity of penem-1 in combination with beta-lactams against blaKPC-possessing Klebsiella pneumoniae isolates.Antimicrobial agents and chemotherapy · 2010Article
- Inhibitor resistance in the KPC-2 beta-lactamase, a preeminent property of this class A beta-lactamase.Antimicrobial agents and chemotherapy · 2010Article
- Three decades of beta-lactamase inhibitors.Clinical microbiology reviews · 2010Review
- The role of a second-shell residue in modifying substrate and inhibitor interactions in the SHV beta-lactamase: a study of ambler position Asn276.Biochemistry · 2009Article
- Efficacy of piperacillin combined with the Penem beta-lactamase inhibitor BLI-489 in murine models of systemic infection.Antimicrobial agents and chemotherapy · 2009Article
- In vitro activity of LK-157, a novel tricyclic carbapenem as broad-spectrum {beta}-lactamase inhibitor.Antimicrobial agents and chemotherapy · 2009Article
- Establishment of in vitro susceptibility testing methodologies and comparative activities of piperacillin in combination with the penem {beta}-lactamase inhibitor BLI-489.Antimicrobial agents and chemotherapy · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Novel penem molecules with heterocycle substitutions at the 6 position via a methylidene linkage were investigated for their activities and efficacy as beta-lactamase inhibitors. The concentrations of these molecules that resulted in 50% inhibition of enzyme activity were 0.4 to 3.1 nM for the TEM-1 enzyme, 7.8 to 72 nM for Imi-1, 1.5 to 4.8 nM for AmpC, and 14 to 260 nM for a CcrA metalloenzyme. All the inhibitors were more stable than imipenem against hydrolysis by hog and human dehydropeptidases. Piperacillin was combined with a constant 4-microg/ml concentration of each inhibitor for MIC determinations. The combinations reduced piperacillin MICs by 2- to 32-fold for extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae strains. The MICs for piperacillin-resistant (MIC of piperacillin, >64 microg/ml) strains of Enterobacter spp., Citrobacter spp., and Serratia spp. were reduced to the level of susceptibility (MIC of piperacillin, < or =16 microg/ml) when the drug was combined with 4, 2, or 1 microg of these penem inhibitors/ml. Protection against acute lethal bacterial infections with class A and C beta-lactamase- and ESBL-producing organisms in mice was also demonstrated with piperacillin plus inhibitor. Median effective doses were reduced by approximately two- to eightfold compared to those of piperacillin alone when the drug was combined with the various inhibitors at a 4:1 ratio. Pharmacokinetic analysis after intravenous administration of the various inhibitors showed mean residence times of 0.1 to 0.5 h, clearance rates of 15 to 81 ml/min/kg, and volumes of distribution between 0.4 and 2.5 liters/kg. The novel methylidene penem molecules inhibit both class A and class C enzymes and warrant further investigation for potential as therapeutic agents when used in combination with a beta-lactam antibiotic.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.