Pharmacokinetic and Pharmacodynamic Modeling Analysis of Delpazolid (LCB01-0371) in Adult Patients with Pulmonary Tuberculosis.

Delpazolid (LCB01-0371) is a novel oxazolidinone derivative with a good safety profile for treating gram-positive pathogenic infections such as Mycobacterium abscessus, a highly pathogenic drug-resistant Mycobacterium. In this study, we evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of delpazolid after 14 days of multiple oral administration, using data from adult patients with pulmonary tuberculosis. 800 mg once a day, 400 mg twice a day, 800 mg twice a day, and 1200 mg once a day delpazolid for 14 days were tested in 63 patients with pulmonary tuberculosis.

Antibacterial Activity of LCB10-0200 against .

is one of the important clinical organisms that causes various infectious diseases, including urinary tract infections, necrotizing pneumonia, and surgical wound infections. The increase in the incidence of multidrug-resistance is a major problem in public healthcare. Therefore, a novel antibacterial agent is needed to treat this pathogen.

In Vitro Activity of a Novel Siderophore-Cephalosporin LCB10-0200 (GT-1), and LCB10-0200/Avibactam, against Carbapenem-Resistant , , , and Strains at a Tertiary Hospital in Korea.

The siderophore-antibiotic conjugate LCB10-0200 (a.k.a.

In Vitro Activity of a Novel Siderophore-Cephalosporin, GT-1 and Serine-Type β-Lactamase Inhibitor, GT-055, against , and spp. Panel Strains.

This study investigates GT-1 (also known as LCB10-0200), a novel-siderophore cephalosporin, inhibited multidrug-resistant (MDR) Gram-negative pathogen, via a Trojan horse strategy exploiting iron-uptake systems. We investigated GT-1 activity and the role of siderophore uptake systems, and the combination of GT-1 and a non-β-lactam β-lactamase inhibitor (BLI) of diazabicyclooctane, GT-055, (also referred to as LCB18-055) against molecularly characterised resistant , and spp. isolates.

Resistome Profiles, Plasmid Typing, and Whole-Genome Phylogenetic Tree Analyses of and Co-Harboring ST617 from a Patient without a History of Farm Exposure in Korea.

Recently, a and co-harboring ST 617 isolate was identified from an asymptomatic carrier in Korea. An 81-year-old female was admitted to a university hospital for aortic cardiac valve repair surgery. Following surgery, she was admitted to the intensive care unit (ICU) for three days, and carbapenem-resistant YMC/2017/02/MS631 was isolated from a surveillance culture (rectal swab).

Phenotypic and Genotypic Characterization of spp. Panel Strains: A Cornerstone to Facilitate Antimicrobial Development.

spp. have emerged as significant pathogens causing nosocomial infections. Treatment of these pathogens has become a major challenge to clinicians worldwide, due to their increasing tendency to antibiotic resistance.

Single-dose Intravenous Safety, Tolerability, and Pharmacokinetics and Absolute Bioavailability of LCB01-0371.

Purpose: LCB01-0371 is a novel broad-spectrum oxazolidinone antibacterial agent under investigation for the treatment of infection by gram-positive pathogens, including methicillin-resistant Staphylococcus aureus. This study evaluated the safety, tolerability, and pharmacokinetics of LCB01-0371 after a single intravenous (IV) infusion and determined its absolute oral bioavailability at a therapeutic dose of 800 mg.

Methods: This study was conducted in 2 parts.

Multiple-dose Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Oral LCB01-0371 in Healthy Male Volunteers.

Purpose: LCB01-0371 is a novel oxazolidinone broad-spectrum antibacterial that is more potent than linezolid against systemic infections in animals. The goal of this investigation was to evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of multiple-dose LCB01-0371 as well as the pharmacokinetic characteristics of a new 400-mg tablet formulation.

Methods: Thirty-two healthy male subjects received BID 400-1600 mg multiple oral dosing of LCB01-0371 (200-mg tablet or 400-mg tablet) for 7 days, and 6 subjects received an 800-mg single oral dose of LCB01-0371 (400-mg tablet).

Effect of food on the pharmacokinetic characteristics of a single oral dose of LCB01-0371, a novel oxazolidinone antibiotic.

Background: LCB01-0371 is a novel oxazolidinone antibiotic that blocks protein production by binding to bacterial 23S ribosomes. This antibiotic is active against Gram-positive bacteria. This study aimed to evaluate the effect of food on the pharmacokinetics (PKs) of LCB01-0371 and evaluate its safety profile.

Pharmacokinetics, Pharmacodynamics, and Tolerability of Single-Dose Oral LCB01-0371, a Novel Oxazolidinone with Broad-Spectrum Activity, in Healthy Volunteers.

LCB01-0371 is a novel oxazolidinone with broad-spectrum activity against Gram-positive pathogens in both studies and animal infection models. The objectives of this study were to evaluate its safety, tolerability, pharmacokinetics, and pharmacodynamics following single ascending doses. Single oral doses of 600 mg linezolid, a placebo, or LCB01-0371 of between 50 mg and 3,200 mg were tested in 69 healthy male subjects.

In Vivo Activity of LCB 01-0699, a Prodrug of LCB 01-0648, against Staphylococcus aureus.

is a novel oxazolidinone compound that shows potent antibacterial activities against most Gram-positive cocci, including the multi-drug resistant . In this study, in vivo activity of , a prodrug, against was evaluated in comparison with that of . The results of the systemic infection study demonstrated that LCB01-0699 was more potent than Linezolid against methicillin-susceptible and -resistant S.

Safety, tolerability and pharmacokinetics of 21 day multiple oral administration of a new oxazolidinone antibiotic, LCB01-0371, in healthy male subjects.

Background: LCB01-0371 is a new oxazolidinone antibiotic, which targets most Gram-positive organisms. High rates of adverse reactions including myelosuppression have been reported for existing oxazolidinones, limiting their long-term use.

Objectives: The safety, tolerability and pharmacokinetics (PK) of 21 day multiple oral administrations of LCB01-0371 in healthy male subjects (clinicaltrials.

Activity of LCB01-0371, a Novel Oxazolidinone, against Mycobacterium abscessus.

is a highly pathogenic drug-resistant rapidly growing mycobacterium. In this study, we evaluated the , intracellular, and activities of LCB01-0371, a novel and safe oxazolidinone derivative, for the treatment of infection and compared its resistance to that of other oxazolidinone drugs. LCB01-0371 was effective against several strains and in a macrophage model of infection.

Antimicrobial activities of LCB10-0200, a novel siderophore cephalosporin, against the clinical isolates of Pseudomonas aeruginosa and other pathogens.

Infections caused by multidrug-resistant bacteria, including Pseudomonas aeruginosa, are threatening public health worldwide. Therefore, a novel antibacterial agent is needed to treat these infections. Here, we investigated the in vitro and in vivo activities of a novel siderophore-conjugated cephalosporin, LCB10-0200, against the clinical isolates of Gram-negative bacteria, including multidrug-resistant P.

In Vitro Activities of LCB 01-0648, a Novel Oxazolidinone, against Gram-Positive Bacteria.

Oxazolidinones are a novel class of synthetic antibacterial agents that inhibit bacterial protein synthesis. Here, we synthesized and tested a series of oxazolidinone compounds containing cyclic amidrazone. Among these compounds, we further investigated the antibacterial activities of LCB01-0648 against drug-susceptible or resistant Gram-positive cocci in comparison with those of six reference compounds.

Panel strain of for beta-lactam antibiotic evaluation: their phenotypic and genotypic characterization.

is responsible for numerous infections caused in hospitals, leading to mortality and morbidity. It has been evolving as a multi-drug resistant pathogen, acquiring multiple resistances such as such as horizontal gene transfer, transposon-mediated insertions or change in outer membrane permeability. Therefore, constant efforts are being carried out to control the infections using various antibiotic therapies.

Molecular epidemiology and resistome analysis of multidrug-resistant ST11 Klebsiella pneumoniae strain containing multiple copies of extended-spectrum β-lactamase genes using whole-genome sequencing.

The aim of this work was to investigate the mechanism responsible for multidrug resistance in ST11 Klebsiella pneumoniae YMC 2013/7/B3993 containing multiple copies of ESBL genes using multiple parallel sequencing technology. In-depth analysis of the strain revealed multiple copies of ESBL genes, 2 copies of blaSHV-12 and 1 copy of blaCTX-M-15. Furthermore, 1 copy of blaOXA-9 and 3 copies of blaTEM-1 were found.

Efficient single-molecule fluorescence resonance energy transfer analysis by site-specific dual-labeling of protein using an unnatural amino acid.

Single-molecule fluorescence resonance energy transfer (smFRET) measurement provides a unique and powerful approach to understand complex biological processes including conformational and structural dynamics of individual biomolecules. For effective smFRET analysis of protein, site-specific dual-labeling with two fluorophores as an energy donor and an acceptor is crucial. Here we demonstrate that site-specific dual-labeling of protein via incorporation of unnatural amino acid provides a clearer picture for the folded and unfolded states of the protein in smFRET analysis than conventional labeling using double cysteines.

In vitro and in vivo activities of LCB01-0371, a new oxazolidinone.

LCB01-0371 is a new oxazolidinone with cyclic amidrazone. In vitro activity of LCB01-0371 against 624 clinical isolates was evaluated and compared with those of linezolid, vancomycin, and other antibiotics. LCB01-0371 showed good activity against Gram-positive pathogens.

Enhanced thermodynamic and kinetic stability of calix[4]arene dimers locked in the cone conformation.

Wide rim tetraurea derivatives (2a,b) have been prepared from a calix[4]arene rigidified in the cone conformation by two diethyleneglycol ether bridges between adjacent oxygens. In comparison to the analogous tetraurea derivatives (3a,b) of a tetrapentoxy calix[4]arene, 2a,b show an increased thermodynamic stability in mixtures of CDCl(3) and DMSO-d(6). Their kinetic stability as expressed by the rate of guest exchange (benzene or cyclohexane against the solvent benzene-d(6)) is also strongly increased by factors of 30-38.