{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:06:27Z","timestamp":1790712387238,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,12,10]],"date-time":"2018-12-10T00:00:00Z","timestamp":1544400000000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2018,12]]},"abstract":"\n Therapeutic drug management is regularly performed for aminoglycosides in an effort to maximize their effectiveness and safety. The ratio of maximum plasma drug concentration to minimum inhibitory concentration (Cmax\/\n MIC<\/jats:styled-content>\n ) has long been regarded as the primary pharmacokinetic\/pharmacodynamic (\n PK<\/jats:styled-content>\n \/\n PD<\/jats:styled-content>\n ) index of clinical efficacy for aminoglycosides due to their concentration\u2010dependent killing. In this review, however, we discuss why the area under the plasma concentration\u2013time curve (\n AUC<\/jats:styled-content>\n )\/\n MIC<\/jats:styled-content>\n ratio may be a more reliable indicator of bacterial killing and clinical efficacy for these agents. The definitive\n AUC<\/jats:styled-content>\n \/\n MIC<\/jats:styled-content>\n efficacy targets for aminoglycosides are less clear, unlike those that exist for fluoroquinolones. Evaluation of available literature suggests that an\n AUC<\/jats:styled-content>\n \/\n MIC<\/jats:styled-content>\n ratio of 30\u201350 for aminoglycoside therapy may provide optimal outcomes when targeting non\u2013critically ill immunocompetent patients with low\u2013bacterial burden gram\u2010negative infections such as urinary tract infections or in patients receiving additional gram\u2010negative therapy with good source control. However, an\n AUC<\/jats:styled-content>\n \/\n MIC<\/jats:styled-content>\n target of 80\u2013100 may be more prudent when treating patients with aminoglycoside monotherapy or in critically ill patients with high\u2013bacterial burden infections, such as nosocomial pneumonia. Reappraisal of current antimicrobial susceptibility breakpoints for aminoglycosides against gram\u2010negative bacteria may also be necessary to achieve these\n AUC<\/jats:styled-content>\n \/\n MIC<\/jats:styled-content>\n targets and ensure that current empiric doses are not grossly suboptimal in critically ill patients. Although it has been historically difficult to calculate\n AUC<\/jats:styled-content>\n s in clinical practice, equation\u2010based and Bayesian approaches now can be used to estimate the\n AUC<\/jats:styled-content>\n in clinical practice, with limited\n PK<\/jats:styled-content>\n sampling. Additional research is needed to better define optimal\n AUC<\/jats:styled-content>\n \/\n MIC<\/jats:styled-content>\n targets for efficacy, especially when drugs are used in combination, as well as\n PK<\/jats:styled-content>\n \/\n PD<\/jats:styled-content>\n targets associated with suppression of resistance. It is also important to determine if\n AUC<\/jats:styled-content>\n can predict nephrotoxicity of these agents or whether trough concentrations should be used instead.\n <\/jats:p>","DOI":"10.1002\/phar.2193","type":"journal-article","created":{"date-parts":[[2018,11,7]],"date-time":"2018-11-07T08:18:45Z","timestamp":1541578725000},"page":"1229-1238","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":98,"title":["Reappraisal of Contemporary Pharmacokinetic and Pharmacodynamic Principles for Informing Aminoglycoside Dosing"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8806-4583","authenticated-orcid":false,"given":"Christopher M.","family":"Bland","sequence":"first","affiliation":[{"name":"Clinical and Administrative Pharmacy University of Georgia College of Pharmacy Savannah Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7119-5034","authenticated-orcid":false,"given":"Manjunath P.","family":"Pai","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy College of Pharmacy University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4730-0655","authenticated-orcid":false,"given":"Thomas P.","family":"Lodise","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice Albany College of Pharmacy and Health Sciences Albany New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1586\/eri.12.25"},{"key":"e_1_2_9_3_1","unstructured":"Sagent Pharmaceuticals.Amikacin sulfate injection USP [package insert].Schaumburg IL;2015."},{"key":"e_1_2_9_4_1","unstructured":"Fresenius Kabi USA LLC.Gentamicin injection USP [package insert].Lake Zurich IL;2013."},{"key":"e_1_2_9_5_1","unstructured":"Pfizer Inc.Tobramycin injection USP [package insert].New York NY;2011."},{"key":"e_1_2_9_6_1","unstructured":"Achaogen Inc.Zemdri [package insert].South San Francisco CA;2018."},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciq257"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw353"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/599376"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-017-4683-6"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000296"},{"key":"e_1_2_9_12_1","first-page":"753","article-title":"Back to the future: using aminoglycosides again and how to dose them optimally","volume":"6","author":"Drusano GL","year":"2007","journal-title":"Clin Infect Dis"},{"key":"e_1_2_9_13_1","first-page":"1135","article-title":"Aminoglycosides for life\u2010threatening infections: a plea for an individualized approach using intensive therapeutic drug monitoring","volume":"10","author":"De Waele JJ","year":"2014","journal-title":"Minerva Anestesiol"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccc.2010.11.006"},{"key":"e_1_2_9_15_1","unstructured":"U.S. Committee on Antimicrobial Susceptibility Testing (USCAST) The National Antimicrobial Susceptibility Testing Committee for the United States.Aminoglycoside in\u00a0vitro susceptibility test interpretive criteria evaluations (version 1.1) July 31 2016. 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