Combination Antibiotic Accelerator (360G-Wellcome-334588_Z_25_Z)

In the midst of a global antimicrobial resistance crisis, development of antibiotics with new modes of action has stalled. Combining existing antibiotics may be the only way to treat multi—and extremely drug-resistant bacteria and prevent new resistant strains emerging. Our Combination Antibiotic Accelerator will deliver a pathfinder for prioritising combinations of antibiotics with therapeutic efficacy and potential to prevent resistance. To maximise immediate translational benefit—and recognising that no single solution will be suitable in all clinical contexts—we will generate a rank order of combinations initially optimised for Southeast Asian countries. We will: 1) Refine selection of target pathogens and antibiotics. 2) Gather and generate evidence on the pharmacokinetic–pharmacodynamic properties of combinations in our target populations, exploiting our world-leading assets in: in vitro and pre-clinical models; clinical trials infrastructure through the ADVANCE-ID platform; and mathematical modelling to predict emerging resistance. 3) Stratify antimicrobial combinations using a utility-based approach, integrating pharmacokinetic–pharmacodynamic data and characteristics such as cost and availability of antibiotics; with dynamic ranking as new data emerge. 4) Work with stakeholders to maximise translation to the clinic. Our dynamic outputs will ensure that clinicians can deliver evidence-based combination antibiotic therapy in an increasingly unpredictable global environment.