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However, as for monotherapy, antibiotic-adjuvant therapies can select for a variety of resistance mechanisms, so it is imperative that adjuvants be used in a sustainable manner. We test whether the rate of resistance evolution can be decoupled from treatment efficacy using co-amoxiclav, a clinically important combination of the \u03b2-lactam amoxicillin and \u03b2-lactamase inhibitor clavulanate. Using experimental evolution and a simple theoretical model, we show that the current co-amoxiclav formulation with a high proportion of amoxicillin rapidly selects for resistance via increased \u03b2-lactamase production. On the other hand, formulations with more clavulanate and less amoxicillin have similar efficacies yet prevent the selective benefit of increased \u03b2-lactamase. We suggest that by blocking common paths to resistance, treatment combinations with the adjuvant in excess can slow the evolution of resistance.<\/jats:p>","DOI":"10.1128\/mbio.01831-19","type":"journal-article","created":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T10:13:52Z","timestamp":1568628832000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["Modified Antibiotic Adjuvant Ratios Can Slow and Steer the Evolution of Resistance: Co-amoxiclav as a Case Study"],"prefix":"10.1128","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6012-7888","authenticated-orcid":false,"given":"Richard C.","family":"Allen","sequence":"first","affiliation":[{"name":"Institute of Integrative Biology, ETH Z\u00fcrich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam P.","family":"Brown","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USA"},{"name":"Center for Microbial Dynamics and Infection, Georgia Institute of Technology, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1034"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3922"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msu191"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00424-7"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2778"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01341-17"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02111-18"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/emph\/eov025"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6601a7"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j254"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14098"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.12478"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0141-x"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2016.06.009"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.1.105-116.2001"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2017.28"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks002"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2014.09.037"},{"key":"e_1_3_2_20_2","volume-title":"WHO model list of essential medicines","author":"World Health Organization","year":"2015","unstructured":"World Health Organization. 2015. 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