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In-vivo antibacterial activity and pharmacological properties of membrane active glycopeptide antibiotic (YV11455)

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Title In-vivo antibacterial activity and pharmacological properties of membrane active glycopeptide antibiotic (YV11455)
Not Available
 
Creator Venkateswarlu Y
Mohini MK
Goutham BM
Relekar GP
Bhuvana M
Krishnamoorthy P
Shome BR
Chakraborty SP
Roy S
Haldar J
 
Subject Antibiotic resistance, Glycopeptide antibiotics, Vancomycin-resistant bacteria, Membrane-active antibiotic, In vivo efficacy, Pharmacological properties
 
Description Not Available
The membrane-active glycopeptide antibiotic YV11455 is a lipophilic cationic vancomycin analogue that demonstrates rapid and concentration-dependent killing of clinically relevant multidrug-resistant (MDR) Gram-positive bacteria in vitro. YV11455 was 2-fold and 54–270-fold more effective than vancomycin against clinical isolates of vancomycin-sensitive and vancomycin-resistant bacteria, respectively. In this study, the in vivo efficacy, pharmacodynamics, pharmacokinetics and acute toxicology of YV11455 were investigated. In vivo activity and pharmacodynamics were determined in the neutropenic mouse thigh infection model against meticillin-resistant Staphylococcus aureus (MRSA). YV11455 produced dose-dependent reductions in MRSA titres in thigh muscle. When administered intravenously, the 50% effective dose (ED50) for YV11455 against MRSA was found to be 3.3 mg/kg body weight, and titres were reduced by up to ca. 3 log10 CFU/g from pre-treatment values at a dosage of 12 mg/kg with single treatment. Single-dose pharmacokinetic studies demonstrated linear kinetics and a prolonged half-life, with an increase in drug exposure (area under the concentration–time curve) compared with vancomycin. The peak plasma concentration following an intravenous dose of 12 mg/kg was 543.5 μg/mL. Acute toxicology studies revealed that YV11455 did not cause any significant alterations in biochemical parameters or histological pictures related to major organs such as the liver and kidney at its pharmacodynamic endpoint (ED3-log kill). These findings collectively suggest that YV11455 could be used clinically for the treatment of infections caused by MDR Gram-positive bacteria.
Not Available
 
Date 2018-09-15T07:07:31Z
2018-09-15T07:07:31Z
2015-03-26
 
Type Research Paper
 
Identifier Not Available
0924-8579
http://krishi.icar.gov.in/jspui/handle/123456789/6887
 
Language English
 
Relation Not Available;
 
Publisher Elsevier Publications