Model-Informed Precision Dosing Improves Outcomes in Patients Receiving Vancomycin for Gram-Positive Infections

Nicole M Hall; Matthew L Brown; W Seth Edwards; Robert A Oster; Will Cordell; Joshua Stripling

doi:10.1093/ofid/ofae002

Model-Informed Precision Dosing Improves Outcomes in Patients Receiving Vancomycin for Gram-Positive Infections

Open Forum Infect Dis. 2024 Jan 5;11(1):ofae002. doi: 10.1093/ofid/ofae002. eCollection 2024 Jan.

Authors

Nicole M Hall¹, Matthew L Brown¹, W Seth Edwards¹, Robert A Oster², Will Cordell³, Joshua Stripling⁴

Affiliations

¹ Department of Pharmacy, UAB Hospital, Birmingham, Alabama, USA.
² Department of Medicine, Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
³ Department of Pharmacy, The University of Kansas Health System, Kansas City, Kansas, USA.
⁴ Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA.

Abstract

Background: Consensus guidelines for dosing and monitoring of vancomycin recommend collection of 2 serum concentrations to estimate an area under the curve/minimum inhibitory concentration ratio (AUC/MIC). Use of Bayesian software for AUC estimation and model-informed precision dosing (MIPD) enables pre-steady state therapeutic drug monitoring using a single serum concentration; however, data supporting this approach are limited.

Methods: Adult patients with culture-proven gram-positive infections treated with vancomycin ≥72 hours receiving either trough-guided or AUC-guided therapy were included in this retrospective study. AUC-guided therapy was provided using MIPD and single-concentration monitoring. Treatment success, vancomycin-associated acute kidney injury (VA-AKI), and inpatient mortality were compared using a desirability of outcome ranking analysis. The most desirable outcome was survival with treatment success and no VA-AKI, and the least desirable outcome was death.

Results: The study population (N = 300) was comprised of an equal number of patients receiving AUC-guided or trough-guided therapy. More patients experienced the most desirable outcome in the AUC-guided group compared to the trough-guided group (58.7% vs 46.7%, P = .037). Rates of VA-AKI were lower (21.3% vs 32.0%, P = .037) and median hospital length of stay was shorter (10 days [interquartile range {IQR}, 8-20] vs 12 days [IQR, 8-25]; P = .025) among patients receiving AUC-guided therapy.

Conclusions: AUC-guided vancomycin therapy using MIPD and single-concentration monitoring improved outcomes in patients with culture-proven gram-positive infections. Safety was improved with reduced incidence of VA-AKI, and no concerns for reduced efficacy were observed. Moreover, MIPD allowed for earlier assessment of AUC target attainment and greater flexibility in the collection of serum vancomycin concentrations.

Keywords: AUC; area under the curve; model-informed precision dosing; therapeutic drug monitoring; vancomycin.