AUCs and 123s: a critical appraisal of vancomycin therapeutic drug monitoring in paediatrics
| Autor: | Kathryn Timberlake, Bruce R Dalton, Jackson J Stewart, Linda Dresser, Alfred S. Gin, Deonne Dersch-Mills, Sarah C J Jorgensen |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
0301 basic medicine Microbiology (medical) Pediatrics medicine.medical_specialty 030106 microbiology Psychological intervention Microbial Sensitivity Tests Target range Nephrotoxicity 03 medical and health sciences 0302 clinical medicine Therapeutic index Vancomycin medicine Humans Pharmacology (medical) 030212 general & internal medicine Dosing Child Pharmacology medicine.diagnostic_test business.industry Bayes Theorem Anti-Bacterial Agents Critical appraisal Infectious Diseases Therapeutic drug monitoring Area Under Curve Drug Monitoring business medicine.drug |
| Zdroj: | Journal of Antimicrobial Chemotherapy. 76:2237-2251 |
| ISSN: | 1460-2091 0305-7453 |
| Popis: | The revised vancomycin guidelines recommend implementing AUC24-based therapeutic drug monitoring (TDM) using Bayesian methods in both adults and paediatrics. The motivation for this change was accumulating evidence showing aggressive dosing to achieve high troughs, as recommended in the first guidelines for adults and extrapolated to paediatrics, is associated with increased nephrotoxicity without improving clinical outcomes. AUC24-based TDM requires substantial resources that may need to be diverted from other valuable interventions. It can therefore be justified only after certain assumptions are shown to be true: (i) there is a clear relationship between vancomycin efficacy and/or toxicity and the proposed therapeutic range; and (ii) maintaining exposure within the target range with AUC24-based TDM improves clinical outcomes and/or decreases toxicity. In this review, we critically appraise the scientific basis for these assumptions. We find studies evaluating the relationship between vancomycin AUC24/MIC and efficacy in adults and children do not offer strong support for the recommended lower limit of the proposed therapeutic range (i.e. AUC24/MIC ≥400). Nephrotoxicity in children increases in a stepwise manner along the vancomycin exposure continuum but it is unclear if one parameter (AUC24 versus trough) is a superior predictor. Overall, evidence in children suggests good-to-excellent correlation between AUC24 and trough. Most importantly, there is no convincing evidence that the method of vancomycin TDM has a causal role in improving efficacy or reducing toxicity. These findings question the need to transition to resource-intensive AUC24-based TDM over retaining trough-based TDM with lower targets to minimize nephrotoxicity in paediatrics. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|