Research priorities towards precision antibiotic therapy to improve patient care.

Antibiotic resistance presents an incessant threat to our drug armamentarium that necessitates novel approaches to therapy. Over the past several decades, investigation of pharmacokinetic and pharmacodynamic (PKPD) principles has substantially improved our understanding of the relationships between the antibiotic, pathogen, and infected patient. However, crucial gaps in our understanding of the pharmacology of antibacterials and their optimal use in the care of patients continue to exist; simply attaining antibiotic exposures that are considered adequate based on traditional targets can still result in treatment being unsuccessful and resistance proliferation for some infections. It is this salient paradox that points to key future directions for research in antibiotic therapeutics. This Personal View discusses six priority areas for antibiotic pharmacology research: (1) antibiotic-pathogen interactions, (2) antibiotic targets for combination therapy, (3) mechanistic models that describe the time-course of treatment response, (4) understanding and modelling of host response to infection, (5) personalised medicine through therapeutic drug management, and (6) application of these principles to support development of novel therapies. Innovative approaches that enhance our understanding of antibiotic pharmacology and facilitate more accurate predictions of treatment success, coupled with traditional pharmacology research, can be applied at the population level and to individual patients to improve outcomes.
Competing Interests: Declaration of interests There was no funding to support this Personal View. JL and RLN licensed their new-generation polymyxin molecules to Qpex Biopharma. JL received grant support, a seminar honorarium, and consultation fees from Northern Antibiotics, Qpex Biopharma, Healthcare Pharmaceuticals, Genentech, and DanDi Bioscience. JBB received research consulting fees from MicuRx Pharmaceuticals and Lupin Pharmaceuticals. All other authors declare no competing interests.
(Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)