Reappraisal of Contemporary Pharmacokinetic and Pharmacodynamic Principles for Informing Aminoglycoside Dosing.

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dc.contributor.authorBland, Christopher M
dc.contributor.authorPai, Manjunath P
dc.contributor.authorLodise, Thomas P
dc.contributor.orcidhttps://orcid.org/0000-0002-4730-0655
dc.date.accessioned2025-02-07T19:35:05Z
dc.date.available2025-02-07T19:35:05Z
dc.date.issued2018-12
dc.descriptionClick on the Resource Link to access the article (may not be free).
dc.description.abstractTherapeutic 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/MIC) has long been regarded as the primary pharmacokinetic/pharmacodynamic (PK/PD) index of clinical efficacy for aminoglycosides due to their concentration-dependent killing. In this review, however, we discuss why the area under the plasma concentration-time curve (AUC)/MIC ratio may be a more reliable indicator of bacterial killing and clinical efficacy for these agents. The definitive AUC/MIC efficacy targets for aminoglycosides are less clear, unlike those that exist for fluoroquinolones. Evaluation of available literature suggests that an AUC/MIC ratio of 30-50 for aminoglycoside therapy may provide optimal outcomes when targeting non-critically ill immunocompetent patients with low-bacterial burden gram-negative infections such as urinary tract infections or in patients receiving additional gram-negative therapy with good source control. However, an AUC/MIC target of 80-100 may be more prudent when treating patients with aminoglycoside monotherapy or in critically ill patients with high-bacterial burden infections, such as nosocomial pneumonia. Reappraisal of current antimicrobial susceptibility breakpoints for aminoglycosides against gram-negative bacteria may also be necessary to achieve these AUC/MIC targets and ensure that current empiric doses are not grossly suboptimal in critically ill patients. Although it has been historically difficult to calculate AUCs in clinical practice, equation-based and Bayesian approaches now can be used to estimate the AUC in clinical practice, with limited PK sampling. Additional research is needed to better define optimal AUC/MIC targets for efficacy, especially when drugs are used in combination, as well as PK/PD targets associated with suppression of resistance. It is also important to determine if AUC can predict nephrotoxicity of these agents or whether trough concentrations should be used instead.
dc.description.urihttps://doi.org/10.1002/phar.2193
dc.identifier.citationBland CM, Pai MP, Lodise TP. Reappraisal of Contemporary Pharmacokinetic and Pharmacodynamic Principles for Informing Aminoglycoside Dosing. Pharmacotherapy. 2018 Dec;38(12):1229-1238. doi: 10.1002/phar.2193. Erratum in: Pharmacotherapy. 2019 Jul;39(7):794. PMID: 30403305.
dc.identifier.issn0277-0008
dc.identifier.other30403305
dc.identifier.urihttps://hdl.handle.net/20.500.14303/815
dc.language.isoen
dc.publisherWiley-Blackwell
dc.relation.ispartofPharmacotherapy
dc.rightsThis Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). http://rightsstatements.org/vocab/InC/1.0/
dc.subjectAminoglycosides/administration & dosage/blood
dc.subjectAnti-Bacterial Agents/administration & dosage/blood
dc.subjectArea Under Curve
dc.subjectBacterial Infections/blood/drug therapy
dc.subjectCritical Illness/therapy
dc.subjectDose-Response Relationship, Drug
dc.subjectMicrobial Sensitivity Tests/methods/standards
dc.titleReappraisal of Contemporary Pharmacokinetic and Pharmacodynamic Principles for Informing Aminoglycoside Dosing.
dc.typeArticle
local.departmentprogramDepartment of Pharmacy Practice
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