Too much of a good thing: defining antimicrobial therapeutic targets to minimize toxicity.

TitleToo much of a good thing: defining antimicrobial therapeutic targets to minimize toxicity.
Publication TypeJournal Article
Year of Publication2021
AuthorsDownes KJ, Goldman JL
JournalClin Pharmacol Ther
Date Published2021 Feb 04
ISSN1532-6535
Abstract

Antimicrobials are a common cause of drug toxicity. 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-defined dose-dependent toxicities, many other exposure-toxicity relationships have either not been well-defined 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-toxicity thresholds and integrate effective TDM strategies has the potential to minimize many of the observed antimicrobials toxicities.

DOI10.1002/cpt.2190
Alternate JournalClin Pharmacol Ther
PubMed ID33539569