Evaluation of the extracellular and intracellular activities (human THP-1 macrophages) of telavancin versus vancomycin against methicillin-susceptible, methicillin-resistant, vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus
Identifieur interne : 001660 ( Main/Exploration ); précédent : 001659; suivant : 001661Evaluation of the extracellular and intracellular activities (human THP-1 macrophages) of telavancin versus vancomycin against methicillin-susceptible, methicillin-resistant, vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus
Auteurs : Maritza Barcia-Macay [Belgique] ; Sandrine Lemaire [Belgique] ; Marie-Paule Mingeot-Leclercq [Belgique] ; Paul M. Tulkens [Belgique] ; Françoise Van Bambeke [Belgique]Source :
- Journal of Antimicrobial Chemotherapy [ 0305-7453 ] ; 2006-12.
Abstract
Objectives: To compare extracellular and intracellular activities of telavancin (versus vancomycin) against Staphylococcus aureus (MSSA, MRSA, VISA and VRSA). Methods: Determination of cfu changes (3–24 h) in culture medium and in macrophages at concentrations ranging from 0.01 to 1000× MIC. Results: Extracellularly, telavancin displayed a fast, concentration-dependent bactericidal activity against all strains. The concentration–effect relationship was bimodal for MSSA and MRSA [two successive sharp drops in bacterial counts (0.3–1× MIC and 100–1000× MIC) separated by a zone of low concentration dependency]. When compared at human total drug Cmax (vancomycin, 50 mg/L; telavancin, 90 mg/L) towards MSSA, MRSA and VISA, telavancin caused both a faster and more marked decrease of cfu, with the limit of detection (>5 log decrease) reached already at 6 versus 24 h for vancomycin. Intracellularly, the bactericidal activity of telavancin was less intense [−3 log (MSSA) to −1.5 log (VRSA) at Cmax and at 24 h]. A bimodal relationship with respect to concentration (at 24 h) was observed for both MSSA and MRSA. In contrast, vancomycin exhibited only marginal intracellular activity towards intraphagocytic MSSA, MRSA and VISA (max. −0.5 log decrease at 24 h and at Cmax). Conclusions: Telavancin showed time- and concentration-dependent bactericidal activity against both extracellular and intracellular S. aureus with various resistance phenotypes. The data support the use of telavancin in infections where intracellular and extracellular S. aureus are present. Bimodality of dose responses (MSSA and MRSA) could indicate multiple mechanisms of action for telavancin.
Url:
DOI: 10.1093/jac/dkl424
Affiliations:
- Belgique
- Province du Brabant wallon, Région wallonne
- Louvain-la-Neuve
- Université catholique de Louvain
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Tulkens</name></author><author><name sortKey="Van Bambeke, Francoise" sort="Van Bambeke, Francoise" uniqKey="Van Bambeke F" first="Françoise" last="Van Bambeke">Françoise Van Bambeke</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:FE9587CE2FD85CCC3DC37FFFBC900BE546154013</idno><date when="2006" year="2006">2006</date><idno type="doi">10.1093/jac/dkl424</idno><idno type="url">https://api.istex.fr/document/FE9587CE2FD85CCC3DC37FFFBC900BE546154013/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000E78</idno><idno type="wicri:Area/Istex/Curation">000E69</idno><idno type="wicri:Area/Istex/Checkpoint">001106</idno><idno type="wicri:doubleKey">0305-7453:2006:Barcia Macay M:evaluation:of:the</idno><idno type="wicri:Area/Main/Merge">001668</idno><idno type="wicri:Area/Main/Curation">001660</idno><idno type="wicri:Area/Main/Exploration">001660</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Evaluation of the extracellular and intracellular activities (human THP-1 macrophages) of telavancin versus vancomycin against methicillin-susceptible, methicillin-resistant, vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus</title><author><name sortKey="Barcia Macay, Maritza" sort="Barcia Macay, Maritza" uniqKey="Barcia Macay M" first="Maritza" last="Barcia-Macay">Maritza Barcia-Macay</name><affiliation wicri:level="4"><country xml:lang="fr">Belgique</country><wicri:regionArea>Unité de Pharmacologie cellulaire et moléculaire, Université catholique de Louvain, B-1200 Brussels</wicri:regionArea><orgName type="university">Université catholique de Louvain</orgName><placeName><settlement type="city">Louvain-la-Neuve</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province du Brabant wallon</region></placeName></affiliation></author><author><name sortKey="Lemaire, Sandrine" sort="Lemaire, Sandrine" uniqKey="Lemaire S" first="Sandrine" last="Lemaire">Sandrine Lemaire</name><affiliation wicri:level="4"><country xml:lang="fr">Belgique</country><wicri:regionArea>Unité de Pharmacologie cellulaire et moléculaire, Université catholique de Louvain, B-1200 Brussels</wicri:regionArea><orgName type="university">Université catholique de Louvain</orgName><placeName><settlement type="city">Louvain-la-Neuve</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province du Brabant wallon</region></placeName></affiliation></author><author><name sortKey="Mingeot Leclercq, Marie Paule" sort="Mingeot Leclercq, Marie Paule" uniqKey="Mingeot Leclercq M" first="Marie-Paule" last="Mingeot-Leclercq">Marie-Paule Mingeot-Leclercq</name><affiliation wicri:level="4"><country xml:lang="fr">Belgique</country><wicri:regionArea>Unité de Pharmacologie cellulaire et moléculaire, Université catholique de Louvain, B-1200 Brussels</wicri:regionArea><orgName type="university">Université catholique de Louvain</orgName><placeName><settlement type="city">Louvain-la-Neuve</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province du Brabant wallon</region></placeName></affiliation></author><author><name sortKey="Tulkens, Paul M" sort="Tulkens, Paul M" uniqKey="Tulkens P" first="Paul M." last="Tulkens">Paul M. 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Methods: Determination of cfu changes (3–24 h) in culture medium and in macrophages at concentrations ranging from 0.01 to 1000× MIC. Results: Extracellularly, telavancin displayed a fast, concentration-dependent bactericidal activity against all strains. The concentration–effect relationship was bimodal for MSSA and MRSA [two successive sharp drops in bacterial counts (0.3–1× MIC and 100–1000× MIC) separated by a zone of low concentration dependency]. When compared at human total drug Cmax (vancomycin, 50 mg/L; telavancin, 90 mg/L) towards MSSA, MRSA and VISA, telavancin caused both a faster and more marked decrease of cfu, with the limit of detection (>5 log decrease) reached already at 6 versus 24 h for vancomycin. Intracellularly, the bactericidal activity of telavancin was less intense [−3 log (MSSA) to −1.5 log (VRSA) at Cmax and at 24 h]. A bimodal relationship with respect to concentration (at 24 h) was observed for both MSSA and MRSA. In contrast, vancomycin exhibited only marginal intracellular activity towards intraphagocytic MSSA, MRSA and VISA (max. −0.5 log decrease at 24 h and at Cmax). Conclusions: Telavancin showed time- and concentration-dependent bactericidal activity against both extracellular and intracellular S. aureus with various resistance phenotypes. The data support the use of telavancin in infections where intracellular and extracellular S. aureus are present. Bimodality of dose responses (MSSA and MRSA) could indicate multiple mechanisms of action for telavancin.</div></front></TEI><affiliations><list><country><li>Belgique</li></country><region><li>Province du Brabant wallon</li><li>Région wallonne</li></region><settlement><li>Louvain-la-Neuve</li></settlement><orgName><li>Université catholique de Louvain</li></orgName></list><tree><country name="Belgique"><region name="Région wallonne"><name sortKey="Barcia Macay, Maritza" sort="Barcia Macay, Maritza" uniqKey="Barcia Macay M" first="Maritza" last="Barcia-Macay">Maritza Barcia-Macay</name></region><name sortKey="Lemaire, Sandrine" sort="Lemaire, Sandrine" uniqKey="Lemaire S" first="Sandrine" last="Lemaire">Sandrine Lemaire</name><name sortKey="Mingeot Leclercq, Marie Paule" sort="Mingeot Leclercq, Marie Paule" uniqKey="Mingeot Leclercq M" first="Marie-Paule" last="Mingeot-Leclercq">Marie-Paule Mingeot-Leclercq</name><name sortKey="Tulkens, Paul M" sort="Tulkens, Paul M" uniqKey="Tulkens P" first="Paul M." last="Tulkens">Paul M. Tulkens</name><name sortKey="Van Bambeke, Francoise" sort="Van Bambeke, Francoise" uniqKey="Van Bambeke F" first="Françoise" last="Van Bambeke">Françoise Van Bambeke</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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