Antimicrobial resistance threatens a resurgence of life-threatening bacterial infections and the potential demise of many aspects of modern medicine. Despite intensive drug discovery efforts, no new classes of antibiotics have been developed into new medicines for decades, in large part owing to the stringent chemical, biological and pharmacological requisites for effective antibiotic drugs. Combinations of antibiotics and of antibiotics with non-antibiotic activity-enhancing compounds offer a productive strategy to address the widespread emergence of antibiotic-resistant strains. In this Review, we outline a theoretical and practical framework for the development of effective antibiotic combinations.
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The authors gratefully acknowledge funding from the Canadian Institutes of Health Research, the Ontario Research Fund, the Bill and Melinda Gates Foundation and the Canada Research Chairs programme. The authors thank E. Brown for terrifically generous and valuable discussions together with M. Spitzer and J. Wildenhain for inspired conversations on machine-learning-based predictions of chemical synergism. C. Groves provided excellent assistance in preparation of figure 2.
Nature Reviews Microbiology thanks A. Typas and the other anonymous reviewer(s) for their contribution to the peer review of this work.