Doctors currently guess which combinations of antibiotics to use against drug-resistant infections, often with little evidence to guide them. This project builds a standardised toolbox of lab tests and computer models to design antibiotic pairings and dosing schedules that kill bacteria effectively while minimising the chance of further resistance emerging. The problem is that combination treatments have been developed empirically—trial and error—and may be suboptimal, wasting drugs and accelerating resistance. COMBAT-AMR will produce open-source computational resources and experimental protocols, then seek regulatory qualification for them. If successful, the toolbox would allow researchers and clinicians to rationally design and test antibiotic combinations before they reach patients, replacing guesswork with data-driven decisions. This could slow the spread of antimicrobial resistance, extend the useful life of existing antibiotics, and improve outcomes for people with complex infections that currently have few treatment options. The project is applied and translational—it directly targets a pressing clinical need rather than exploring fundamental mechanisms.
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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.
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