title: Selection and evolution of resistance to antimicrobial drugs.
abstract: The overuse and misuse of antibiotics over many years has selected a high frequency of resistance among medically important bacterial pathogens. The evolution of resistance is complex, frequently involving multiple genetic alterations that minimize biological fitness costs and/or increase the resistance level. Resistance is selected at very low drug concentrations, such as found widely distributed in the environment, and this selects for resistant mutants with a high fitness. Once resistance with high fitness is established in a community it is very difficult to reduce its frequency. Addressing the problem of resistance is essential if we are to ensure a future where we can continue to enjoy effective medical control of bacterial infections. This will require several actions including the discovery and development of novel antibiotics, the creation of a continuous pipeline of drug discovery, and the implementation of effective global antibiotic stewardship to reduce the misuse of antibiotics and their release into the environment.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Uppsala, Sweden.
authors.forename: Diarmaid
authors.initials: D
authors.lastname: Hughes
mesh_terms: D000890:Anti-Infective Agents; D005075:Biological Evolution; D055808:Drug Discovery / Q000379:methods / Q000639:trends; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005060:Europe; D056084:Genetic Fitness / Q000235:genetics*; D057970:Inappropriate Prescribing / Q000706:statistics & numerical data / Q000639:trends; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D012641:Selection, Genetic / Q000235:genetics*
chemical_list: D000890:Anti-Infective Agents
keywords: antibiotic; evolution; fitness; fluoroquinolone; resistance; rifampicin; sub-MIC