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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. \u00a9 2014 IUBMB Life, 66(8):521\u2013529, 2014<\/jats:p>","DOI":"10.1002\/iub.1278","type":"journal-article","created":{"date-parts":[[2014,6,17]],"date-time":"2014-06-17T00:07:22Z","timestamp":1402963642000},"page":"521-529","source":"Crossref","is-referenced-by-count":44,"title":["Selection and evolution of resistance to antimicrobial drugs"],"prefix":"10.1002","volume":"66","author":[{"given":"Diarmaid","family":"Hughes","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology Biomedical Center, Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,6,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3810\/pgm.2014.03.2737"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.2165\/11591980-000000000-00000"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(08)70284-6"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(09)70135-5"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-011-1592-5"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/2050-6511-15-6"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/tmi.12123"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2710.2011.01293.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1586\/17476348.2013.814411","article-title":"The future of antimicrobial therapy in the era of antibiotic resistance in cystic fibrosis pulmonary infection","volume":"7","author":"McCaughey G.","journal-title":"Exp. 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