Combination therapy development toolbox against antimicrobial resistance (COMBAT-AMR)
Lead Research Organisation:
University College London
Abstract
Antibiotic combination treatment is an essential strategy to combat complex, antimicrobial resistant (AMR) infections. To date, antibiotic combination treatments have been derived empirically and may be suboptimal. Defining the optimal drug combination of antibiotics and the associated dosing schedules to maximise efficacy and minimise the risk for AMR selection is complex and requires extensive preclinical
development. To advance development and optimisation of antibiotic combination treatments, and exploit their underused potential, there is an urgent need for standardised, regulatory-endorsed experimental and computational pharmacokinetic/pharmacodynamic (PK/PD) methodologies. The COMBAT-AMR project aims to develop a standardised toolbox of connected experimental and computational approaches
tailored to the pre-clinical design of antibiotic combination treatments. The unique integrative approach proposed will enable the efficient, rational translational development of antibacterial combinations, which are optimised towards treatment of AMR-associated bacterial infections and preventing AMR emergence. The workflows established in COMBAT-AMR will be applied to several exemplar antibiotic combination treatments to further evaluate and optimise their potential, and to demonstrate the application of the toolbox. The project will result in experimental protocols and open-source computational modelling resources for which we will seek regulatory qualification and support for clinical combination breakpoint determination to optimise clinical and investigational application.
development. To advance development and optimisation of antibiotic combination treatments, and exploit their underused potential, there is an urgent need for standardised, regulatory-endorsed experimental and computational pharmacokinetic/pharmacodynamic (PK/PD) methodologies. The COMBAT-AMR project aims to develop a standardised toolbox of connected experimental and computational approaches
tailored to the pre-clinical design of antibiotic combination treatments. The unique integrative approach proposed will enable the efficient, rational translational development of antibacterial combinations, which are optimised towards treatment of AMR-associated bacterial infections and preventing AMR emergence. The workflows established in COMBAT-AMR will be applied to several exemplar antibiotic combination treatments to further evaluate and optimise their potential, and to demonstrate the application of the toolbox. The project will result in experimental protocols and open-source computational modelling resources for which we will seek regulatory qualification and support for clinical combination breakpoint determination to optimise clinical and investigational application.