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Understanding the relationship between systemic antimicrobial exposure and toxicity is necessary to enable providers to take a proactive approach to prevent undesired drug effects. When an exposure threshold has been defined that predicts drug toxicity, therapeutic drug monitoring (TDM) can be performed to assure drug exposure does not exceed the defined threshold. Although some antimicrobials have well\u2010defined dose\u2010dependent toxicities, many other exposure\u2010toxicity relationships have either not been well\u2010defined or, in some cases, not been evaluated at all. In this review, we examine the relationship between exposures and toxicities for antibiotic, antifungal, and antiviral agents. Furthermore, we classify these relationships into four categories: known association between drug exposure and toxicity such that clinical implementation of a specific exposure threshold associated with toxicity for TDM is supported (category 1), known association between drug exposure and toxicity but the specific exposure threshold associated with toxicity is undefined (category 2), association between drug exposure and toxicity has been suggested but relationship is poorly defined (category 3), and no known association between drug exposure and toxicity (category 4). Further work to define exposure\u2010toxicity thresholds and integrate effective TDM strategies has the potential to minimize many of the observed antimicrobial toxicities.<\/jats:p>","DOI":"10.1002\/cpt.2190","type":"journal-article","created":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T17:59:05Z","timestamp":1612547945000},"page":"905-917","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Too Much of a Good Thing: Defining Antimicrobial Therapeutic Targets to Minimize Toxicity"],"prefix":"10.1111","volume":"109","author":[{"given":"Kevin J.","family":"Downes","sequence":"first","affiliation":[{"name":"The Center for Clinical Pharmacology Children\u2019s Hospital of Philadelphia Philadelphia Pennsylvania USA"},{"name":"The Center for Pediatric Clinical Effectiveness Children\u2019s Hospital of Philadelphia Philadelphia Pennsylvania USA"},{"name":"Division of Infectious Diseases Children\u2019s Hospital of Philadelphia Philadelphia Pennsylvania USA"},{"name":"Department of Pediatrics Perelman School of Medicine of the University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Goldman","sequence":"additional","affiliation":[{"name":"Divisions of Clinical Pharmacology, Toxicology and Therapeutic Innovation and Infectious Diseases Children\u2019s Mercy Kansas City Kansas City Missouri USA"},{"name":"Department of Pediatrics University of Missouri \u2013 Kansas City Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,27]]},"reference":[{"key":"e_1_2_10_1_1","unstructured":"Centers for Disease Control and Prevention.Adverse Drug Events Associated with Specific Medications<https:\/\/www.cdc.gov\/medicationsafety\/adverse\u2010drug\u2010events\u2010specific\u2010medicines.html>. 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