{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T18:08:23Z","timestamp":1777572503469,"version":"3.51.4"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI079578"],"award-info":[{"award-number":["R01 AI079578"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            We are in a crisis of bacterial resistance. For economic reasons, most pharmaceutical companies are abandoning antimicrobial discovery efforts, while, in health care itself, infection control and antibiotic stewardship programs have generally failed to prevent the spread of drug-resistant bacteria. At this point, what can be done? The first step has been taken. Governments and international bodies have declared there is a worldwide crisis in antibiotic drug resistance. As discovery efforts begin anew, what more can be done to protect newly developing agents and improve the use of new drugs to suppress resistance emergence? A neglected path has been the use of recent knowledge regarding antibiotic dosing as single agents and in combination to minimize resistance emergence, while also providing sufficient early bacterial kill. In this review, we look at the data for resistance suppression. Approaches include increasing the intensity of therapy to suppress resistant subpopulations; developing concepts of clinical breakpoints to include issues surrounding suppression of resistance; and paying attention to the duration of therapy, which is another important issue for resistance suppression. New understanding of optimizing combination therapy is of interest for difficult-to-treat pathogens like\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pseudomonas aeruginosa<\/jats:named-content>\n            ,\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Acinetobacter<\/jats:named-content>\n            spp., and multidrug-resistant (MDR)\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Enterobacteriaceae<\/jats:named-content>\n            . These lessons need to be applied to our old drugs to preserve them as well and need to be put into national and international antibiotic resistance strategies. As importantly, from a regulatory perspective, new chemical entities should have a corresponding resistance suppression plan at the time of regulatory review. In this way, we can make the best of our current situation and improve future prospects.\n          <\/jats:p>","DOI":"10.1128\/aac.02177-15","type":"journal-article","created":{"date-parts":[[2015,12,29]],"date-time":"2015-12-29T03:23:15Z","timestamp":1451359395000},"page":"1183-1193","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":54,"title":["Suppression of Emergence of Resistance in Pathogenic Bacteria: Keeping Our Powder Dry, Part 1"],"prefix":"10.1128","volume":"60","author":[{"given":"G. L.","family":"Drusano","sequence":"first","affiliation":[{"name":"Institute for Therapeutic Innovation, University of Florida, Orlando, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnold","family":"Louie","sequence":"additional","affiliation":[{"name":"Institute for Therapeutic Innovation, University of Florida, Orlando, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alasdair","family":"MacGowan","sequence":"additional","affiliation":[{"name":"Bristol Centre for Antimicrobial Research and Evaluation, Department of Microbiology, Southmead Hospital, Bristol, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Hope","sequence":"additional","affiliation":[{"name":"Antimicrobial Pharmacodynamics and Therapeutics, Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/524891"},{"key":"e_1_3_1_3_2","volume-title":"Annual report of the Chief Medical Officer","author":"Davies SC","year":"2013","unstructured":"Davies SC. 2013. Infections and the rise of antimicrobial resistance. Annual report of the Chief Medical Officer, vol 2, 2011. Department of Health, London, United Kingdom."},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/595011"},{"key":"e_1_3_1_5_2","volume-title":"Public health action plan to combat antimicrobial resistance","author":"Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) Division of Healthcare Quality Promotion (DHQP)","year":"2014","unstructured":"Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) Division of Healthcare Quality Promotion (DHQP). 2014. Public health action plan to combat antimicrobial resistance. Centers for Disease Control and Prevention, Atlanta, GA."},{"key":"e_1_3_1_6_2","unstructured":"Innovative Medicines Initiative. 2010. COMBACTE (Combating Bacterial Resistance in Europe). 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