Pharmacokinetic-pharmacodynamic modelling to investigate in vitro synergy between colistin and fusidic acid against MDR Acinetobacter baumannii.
dc.contributor.author | Phee, LM | |
dc.contributor.author | Kloprogge, F | |
dc.contributor.author | Morris, R | |
dc.contributor.author | Barrett, J | |
dc.contributor.author | Wareham, DW | |
dc.contributor.author | Standing, JF | |
dc.date.accessioned | 2019-03-14T10:43:50Z | |
dc.date.available | 2018-11-16 | |
dc.date.available | 2019-03-14T10:43:50Z | |
dc.date.issued | 2019-01-08 | |
dc.identifier.citation | Lynette M Phee, Frank Kloprogge, Rebecca Morris, John Barrett, David W Wareham, Joseph F Standing; Pharmacokinetic-pharmacodynamic modelling to investigate in vitro synergy between colistin and fusidic acid against MDR Acinetobacter baumannii, Journal of Antimicrobial Chemotherapy, , dky524, https://doi.org/10.1093/jac/dky524 | en_US |
dc.identifier.issn | 1460-2091 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/56193 | |
dc.description.abstract | Objectives: The potential for synergy between colistin and fusidic acid in the treatment of MDR Acinetobacter baumannii has recently been shown. The aim of this study was to perform an extensive in vitro characterization of this effect using pharmacokinetic-pharmacodynamic modelling (PKPD) of time-kill experiments in order to estimate clinical efficacy. Methods: For six clinical strains, 312 individual time-kill experiments were performed including 113 unique pathogen-antimicrobial combinations. A wide range of concentrations (0.25-8192 mg/L for colistin and 1-8192 mg/L for fusidic acid) were explored, alone and in combination. PKPD modelling sought to quantify synergistic effects. Results: A PKPD model confirmed synergy in that colistin EC50 was found to decrease by 83% in the presence of fusidic acid, and fusidic acid maximum increase in killing rate (Emax) also increased 58% in the presence of colistin. Simulations indicated, however, that at clinically achievable free concentrations, the combination may be bacteriostatic in colistin-susceptible strains, but growth inhibition probability was <20% in a colistin-resistant strain. Conclusions: Fusidic acid may be a useful agent to add to colistin in a multidrug combination for MDR Acinetobacter baumannii. | en_US |
dc.language | eng | |
dc.language.iso | en | en_US |
dc.publisher | Oxford University Press | en_US |
dc.relation.ispartof | J Antimicrob Chemother | |
dc.rights | This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. | |
dc.rights | Attribution 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
dc.title | Pharmacokinetic-pharmacodynamic modelling to investigate in vitro synergy between colistin and fusidic acid against MDR Acinetobacter baumannii. | en_US |
dc.type | Article | en_US |
dc.rights.holder | © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. | |
dc.identifier.doi | 10.1093/jac/dky524 | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/30624656 | en_US |
pubs.notes | No embargo | en_US |
pubs.publication-status | Published online | en_US |
pubs.publisher-url | https://doi.org/10.1093/jac/dky524 | |
dcterms.dateAccepted | 2018-11-16 | |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |
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Except where otherwise noted, this item's license is described as This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.