CO-ACTION, funded by the Swedish research council within the framework of JPIAMR
The CO-ACTION project aims to develop and provide a framework for evaluating and validating the effectiveness of antibiotic and non-antibiotic combinations (COMs) in the preclinical setting based on pharmacokinetic/pharmacodynamic principles. The interaction between existing antibiotics from at least 6 different classes will be determined for Gram-negative multidrug-resistant strains and analysed by interaction modelling. Synergistic COMs will be further quantified using time-kill curves and applying mechanistic PKPD modelling to predict effective dosing regimens in vivo. Mechanisms of interaction and potential emergence of resistance will be explored. Effectiveness of the most promising 3-6 COMs will be determined in up to 5 available animal model systems. The potential of the COMs in patients will be evaluated by Monte Carlo Simulations using derived PKPD relationships, PD targets and suggest clinical breakpoints for COMs.
Collaborators: Johan Mouton (coordinator), Erasmus University, Lena Friberg, Uppsal University, Francoise van Bambeke, Université Catholique de Louvain, William Couet, Université de Poitiers, Alain Bousquét-Melou, National veterinary school INRA, Toulouse
Screening for effective combinations against clinical multidrug-resistant strains, funded by AFA insurance and the Public Health Agency of Sweden
Clinical isolates of carbapenem-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa provided by the Public Health are exposed to multiple antibiotics including colistin and other antibiotics. Various in vitro methods, including automated microscopy and image analysis, optical density and viable counts are used and differences with these methods are assessed, as well as the potential to use them in a high-throughput screening. The first studies within this project show that automated microscopy may be useful to screen for antibacterial effects with single antibiotics and combinations. Promising combinations have been identified including colistin and other drugs that will be further explored. Other combinations, often used in clinical practice have failed to show effective in these experiments.
Collaborators: Elisabet Nielsen, Uppsala University
QuickMIC - Rapid antibiotic susceptibility testing, funded by Vinnova and AFA insurance
Rapid diagnostic tools are needed to reduce the time to result in antibiotic susceptibility testing. In this project, a new method with the potential to generate MIC results within a few hours is developed and evaluated. Preliminary results show a high level of accuracy and consistent results with conventional methods including Etest and macrodilution.
Collaborators: Sara Thorslund, Gradientech AB, Uppsala, Gunnar Kahlmeter, EUCAST development laboratory, Växjö