In vitro and in vivo activity of LY 146032, a new cyclic lipopeptide antibiotic

Eliopoulos, George M.; Willey, Sandra; Reiszner, E; Spitzer, Peter; Caputo, Gregory A.; Moellering, R C

doi:10.1128/aac.30.4.532

Cited by 165 publications

(122 citation statements)

References 6 publications

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“…These drugs are similar to vancomycin chemically and in mechanism of action and spectrum of activity. In vitro and in animal models, both are active against methicillin-susceptible and -resistant staphylococci (2,36,57,95). Teicoplanin, which can be given intramuscularly once a day, has been effective in some cases of moderately severe staphylococcal infections.…”

Section: Fusidic Acidmentioning

confidence: 99%

Methicillin-resistant staphylococci

1988

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Strains of staphylococci resistant to methicillin were identified immediately after introduction of this drug. Methicillin-resistant strains have unusual properties, the most notable of which is extreme variability in expression of the resistance trait. The conditions associated with this heterogeneous expression of resistance are described. Methicillin resistance is associated with production of a unique penicillin-binding protein (PBP), 2a, which is bound and inactivated only at high concentrations of beta-lactam antibiotics. PBP2a appears to be encoded by the mec determinant, which also is unique to methicillin-resistant strains. The relationships between PBP2a and expression of resistance and implications for the mechanism of resistance are discussed. The heterogeneous expression of methicillin resistance by staphylococci poses problems in the detection of resistant strains. Experience with several susceptibility test methods is reviewed and guidelines for performance of these tests are given. Treatment of infections caused by methicillin-resistant staphylococci is discussed. Vancomycin is the treatment of choice. Alternatives have been few because methicillin-resistant strains often are resistant to multiple antibiotics in addition to beta-lactam antibiotics. New agents which are active against methicillin-resistant staphylococci are becoming available, and their potential role in treatment is discussed.

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Section: Fusidic Acidmentioning

confidence: 99%

Methicillin-resistant staphylococci

1988

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“…Another difficult aspect in undertaking NMR structural studies was carrying out characterization of daptomycin under conditions in which the lipopeptide is most active, i.e. in the presence of high concentrations of Ca 2+ [46][47][48]. With the Ca 2+ /daptomycin molar ratio at 1:1 under these conditions, oligomerization occurs, resulting in 14 to 16 monomers forming micelles [35,49,50].…”

Section: Daptomycin and Derivativesmentioning

confidence: 99%

Lipopeptides as anti-infectives: a practical perspective

et al. 2009

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Abstract:Lipopeptide antibiotics represent an old class of antibiotics that were discovered over 50 years ago, which includes the old polymyxins but also new entries, such as the recently approved daptomycin. They generally consist of a hydrophilic cyclic peptide portion attached to a fatty acid chain which facilitates insertion into the lipid bilayer of bacterial membranes. This review presents an overview of this class of antibiotics, focusing on their therapeutic applications and putting particular emphasis on chemical modifications introduced to improve their activity.

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“…The effect of calcium on the action mechanism of DPT was initially reported in 1986 (Eliopoulos et al, 1986). A subsequent study demonstrated that DPT MICs are generally twofold to fourfold lower when tested in broth containing 50 µg mL -1 of calcium (Fuchs, Barry, Brown, 2000).…”

Section: Calcium Concentrationmentioning

confidence: 99%

“…The molecule is obtained from a strain of Streptomyces roseosporus and was originally known as LY 146032 (Debono et al, 1987;Eliopoulos et al, 1986). The action mechanism is physiologic calcium dependent and possibly involves the disruption of amino acid transport by the cell membrane and changes in the cytoplasmic membrane potential (Debono et al, 1987;Koeth, Thorne, 2010;Lu et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

A fully validated microbiological assay for daptomycin injection and comparison to HPLC method

Christ

Machado

Ribas

et al. 2015

Braz. J. Pharm. Sci.

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Daptomycin (DPT) was the first lipopeptide antibiotic available for commercialization. It is active against gram-positive bacteria, including resistant strains. This work aimed to develop and validate a turbidimetric microbiologic assay to determine daptomycin in an injectable form. A 3x3 design was employed, at concentrations of 1, 2 and 4.0 µg/mL. The microorganism test used was Staphylococcus aureus ATCC 6538p, and Antibiotic Medium 3 was used as the culture medium. Method validation demonstrated that the bioassay was linear (r=0.9995), precise (RSD=2.58%), accurate (recovery 100.48± 2.11%), and robust. Degradation kinetics was also performed in an alkaline medium, indicating that daptomycin degradation follows first order kinetics under these conditions. The analyses of degraded solutions showed that daptomycin degradation products do not possess bactericidal activity. The bioassay was compared to HPLC method that was previously developed and no significant difference was found between them (p>0.05). The method proved to be appropriate for daptomycin injection quality control.Uniterms: Daptomycin/determination. Daptomycin injection/quality control. Turbidimetric microbiological assay/quantitative analysis.A daptomicina (DPT) é o primeiro lipopeptídeo cíclico disponível para comercialização. Possui atividade frente a bactérias gram-positivas, incluindo cepas resistentes. O objetivo deste trabalho foi desenvolver e validar um ensaio microbiológico turbidimétrico para quantificar a daptomicina na forma injetável. Empregou-se delineamento 3x3, nas concentrações de 1,0; 2,0 e 4,0 µg/mL. Como micro-organismo teste foi usado Staphylococcus aureus ATCC 6538p, e Meio para Antibióticos nº 3 foi empregado como meio de cultura. A validação do método demonstrou que o ensaio foi linear (r=0,9995), preciso (RSD=2,55%), exato (recuperação de 100,48 ± 2,11%) e robusto. A cinética de degradação em meio alcalino foi avaliada, indicando que a daptomicina segue cinética de primeira ordem nessa condição. A análise das soluções degradadas mostrou que os produtos de degradação da daptomicina não possuem atividade antimicrobiana. O bioensaio foi comparado com o método por CLAE previamente desenvolvido e não houve diferença significativa entre ambos (p<0,05). O método mostrou-se apropriado para o controle de qualidade da daptomicina injetável.Unitermos: Daptomicina/determinação. Daptomicina injetável/controle de qualidade. Ensaio microbiológico turbidimétrico/análise quantitativa.

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In vitro and in vivo activity of LY 146032, a new cyclic lipopeptide antibiotic

Cited by 165 publications

References 6 publications

Methicillin-resistant staphylococci

Methicillin-resistant staphylococci

Lipopeptides as anti-infectives: a practical perspective

A fully validated microbiological assay for daptomycin injection and comparison to HPLC method

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