Defining the Active Fraction of Daptomycin against Methicillin-Resistant Staphylococcus aureus (MRSA) Using a Pharmacokinetic and Pharmacodynamic Approach
Publication Date
June 10, 2016
Journal
PLOS ONE
Authors
Samira M. Garonzik, Justin R. Lenhard, Alan Forrest, Patricia N. Holden, et al
Volume
11
Issue
6
Pages
e0156131
DOI
https://dx.plos.org/10.1371/journal.pone.0156131
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0156131
Scopus
84976314196
Mendeley
http://www.mendeley.com/research/defining-active-fraction-daptomycin-against-methicillinresistant-staphylococcus-aureus-mrsa-using-ph
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Mendeley | Further Information

{"title"=>"Defining the active fraction of daptomycin against methicillin-resistant staphylococcus aureus (MRSA) using a pharmacokinetic and pharmacodynamic approach", "type"=>"journal", "authors"=>[{"first_name"=>"Samira M.", "last_name"=>"Garonzik", "scopus_author_id"=>"37037420400"}, {"first_name"=>"Justin R.", "last_name"=>"Lenhard", "scopus_author_id"=>"56494667000"}, {"first_name"=>"Alan", "last_name"=>"Forrest", "scopus_author_id"=>"16934667300"}, {"first_name"=>"Patricia N.", "last_name"=>"Holden", "scopus_author_id"=>"7006622211"}, {"first_name"=>"Jürgen B.", "last_name"=>"Bulitta", "scopus_author_id"=>"6603382423"}, {"first_name"=>"Brian T.", "last_name"=>"Tsuji", "scopus_author_id"=>"10041873800"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84976314196", "sgr"=>"84976314196", "pui"=>"610895389", "doi"=>"10.1371/journal.pone.0156131"}, "id"=>"897dae3c-9ce3-3212-9be2-87a47b4a0010", "abstract"=>"© 2016 Garonzik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Our objective was to study the pharmacodynamics of daptomycin in the presence of varying concentrations of human serum (HS) in vitro to quantify the fraction of daptomycin that is 'active'. Time kill experiments were performed with daptomycin (0 to 256 mg/L) against two MRSA strains at log-phase growth, in the presence of HS (0%, 10%, 30%, 50%, 70%) combined with Mueller-Hinton broth. Daptomycin ≥ 2 mg/L achieved 99.9% kill within 8 h at all HS concentrations; early killing activity was slightly attenuated at higher HS concentrations. After 1 h, bacterial reduction of USA300 upon exposure to daptomycin 4 mg/L ranged from -3.1 to -0.5 log01CFU/mL in the presence of 0% to 70% HS, respectively. Bactericidal activity was achieved against both strains at daptomycin ≥ 4 mg/L for all fractions of HS exposure. A mechanism-based mathematical model (MBM) was developed to estimate the active daptomycin fraction at each %HS, comprising 3 bacterial subpopulations differing in daptomycin susceptibility. Time-kill data were fit with this MBM with excellent precision (r 2 > 0.95). The active fraction of daptomycin was estimated to range from 34.6% to 25.2% at HS fractions of 10% to 70%, respectively. Despite the reported low unbound fraction of daptomycin, the impact of protein binding on the activity of daptomycin was modest. The active fraction approach can be utilized to design in vitro experiments and to optimize therapeutic regimens of daptomycin in humans.", "link"=>"http://www.mendeley.com/research/defining-active-fraction-daptomycin-against-methicillinresistant-staphylococcus-aureus-mrsa-using-ph", "reader_count"=>5, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>1, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>1, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Agricultural and Biological Sciences"=>2, "Medicine and Dentistry"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>0}

Scopus | Further Information

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Scopus
Time
2019-08-27 20:06:58 UTC
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