Phee, LM;
Kloprogge, F;
Morris, R;
Barrett, J;
Wareham, DW;
Standing, JF;
(2019)
Pharmacokinetic-pharmacodynamic modelling to investigate in vitro synergy between colistin and fusidic acid against MDR Acinetobacter baumannii.
Journal of Antimicrobial Chemotherapy
, 74
(4)
, Article dky524. 10.1093/jac/dky524.
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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.
| Type: | Article |
|---|---|
| Title: | Pharmacokinetic-pharmacodynamic modelling to investigate in vitro synergy between colistin and fusidic acid against MDR Acinetobacter baumannii |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/jac/dky524 |
| Publisher version: | https://doi.org/10.1093/jac/dky524 |
| Language: | English |
| Additional information: | © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. 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. |
| Keywords: | colistin fusidic acid pharmacodynamics acinetobacter baumannii |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10065899 |
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