Douglas D DeCarolis1, Joey G Thorson, Rebecca A Marraffa, Megan A Clairmont, Michael A Kuskowski. 1. *Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota; †Geriatric Research Education and Clinical Center, Minneapolis Veterans Affairs Medical Center, Minneapolis, Minnesota; and ‡Department of Psychiatry, University of Minnesota Medical School, Twin Cities, Minnesota.
Abstract
BACKGROUND: Vancomycin dose selection is challenging in the spinal cord injury (SCI) population because of the difficulty in accurately estimating the renal function. Creatinine-based equations have been shown to be unreliable in this patient population. Adjusted equations designed for patients with SCI have not been well studied. Cystatin C is an alternative marker of renal function that is less affected by muscle mass and may offer improvement in estimating renal function leading to improved initial dose selection. OBJECTIVE: To compare the accuracy of serum creatinine- and serum cystatin C-based equations used in a pharmacokinetic (PK) model to predict steady-state serum vancomycin concentration in an SCI population. The rationale for this study is the need for an improved predictive model to guide initial vancomycin dose design before the availability of a measured steady-state serum concentration. METHODS: Patients with SCI receiving vancomycin with measured serum creatinine, cystatin C, and steady-state serum vancomycin concentration were identified. Serum creatinine- and cystatin C-based equations to estimate renal function were substituted into a population-based PK model to predict steady state-serum vancomycin concentration. Predictions using each equation in the model were compared with the measured steady-state serum vancomycin concentration. Predictive performances using each equation in the PK model were compared. RESULTS: The final study population included 37 patients with SCI. The Chronic Kidney Disease Epidemiology Collaboration cystatin C equation provided significantly less bias, greater precision, and superior accuracy when used in the PK model. CONCLUSIONS: In the SCI population, the use of Chronic Kidney Disease Epidemiology Collaboration cystatin C equation may improve initial vancomycin dosing. Further study into this potential is encouraged.
BACKGROUND:Vancomycin dose selection is challenging in the spinal cord injury (SCI) population because of the difficulty in accurately estimating the renal function. Creatinine-based equations have been shown to be unreliable in this patient population. Adjusted equations designed for patients with SCI have not been well studied. Cystatin C is an alternative marker of renal function that is less affected by muscle mass and may offer improvement in estimating renal function leading to improved initial dose selection. OBJECTIVE: To compare the accuracy of serum creatinine- and serum cystatin C-based equations used in a pharmacokinetic (PK) model to predict steady-state serum vancomycin concentration in an SCI population. The rationale for this study is the need for an improved predictive model to guide initial vancomycin dose design before the availability of a measured steady-state serum concentration. METHODS:Patients with SCI receiving vancomycin with measured serum creatinine, cystatin C, and steady-state serum vancomycin concentration were identified. Serum creatinine- and cystatin C-based equations to estimate renal function were substituted into a population-based PK model to predict steady state-serum vancomycin concentration. Predictions using each equation in the model were compared with the measured steady-state serum vancomycin concentration. Predictive performances using each equation in the PK model were compared. RESULTS: The final study population included 37 patients with SCI. The Chronic Kidney Disease Epidemiology Collaboration cystatin C equation provided significantly less bias, greater precision, and superior accuracy when used in the PK model. CONCLUSIONS: In the SCI population, the use of Chronic Kidney Disease Epidemiology Collaboration cystatin C equation may improve initial vancomycin dosing. Further study into this potential is encouraged.
Authors: Hilary R Teaford; Ryan W Stevens; Andrew D Rule; Kristin C Mara; Kianoush B Kashani; John C Lieske; John O'Horo; Erin F Barreto Journal: Antimicrob Agents Chemother Date: 2020-12-16 Impact factor: 5.191