Effect of Cystatin C on Vancomycin Clearance Estimation in Critically Ill Children Using a Population Pharmacokinetic Modeling Approach.

TitleEffect of Cystatin C on Vancomycin Clearance Estimation in Critically Ill Children Using a Population Pharmacokinetic Modeling Approach.
Publication TypeJournal Article
Year of Publication2020
AuthorsDownes KJ, Zane NR, Zuppa AF
JournalTher Drug Monit
Date Published2020 Sep 15
ISSN1536-3694
Abstract

BACKGROUND: Vancomycin is eliminated via glomerular filtration, but current approaches to estimate kidney function in children are unreliable. The authors sought to compare the suitability of cystatin C (CysC)-based glomerular filtration rate equations with the most commonly used creatinine-based equation, bedside Schwartz, to estimate vancomycin clearance (CL).

METHODS: This prospective observational study enrolled critically ill patients (2-18 years) receiving intravenous (IV) vancomycin at the Children's Hospital of Philadelphia during December 2015-November 2017. Vancomycin levels were collected during clinical care and at 3 times during a single dosing interval. Plasma CysC was measured within 24 hours prior to IV vancomycin (baseline) initiation or immediately following enrollment, as well as along with the third pharmacokinetic (PK) sample. Nonlinear mixed effects modeling was performed using NONMEM software. Covariate selection was used to test model fit with inclusion of estimated glomerular filtration rate (eGFR) on CL using bedside Schwartz versus various published CysC-based equations.

RESULTS: In total, 83 vancomycin levels were obtained from 20 children. Median age was 12.7 years; 6 patients were female. A one-compartment model best described the data; CL was allometrically scaled to 0.75. During covariate selection, inclusion of eGFR calculated using a CysC-based equation significantly improved model fit (reduction in objective function value [OFV] range: -17.191 to -18.704) than bedside Schwartz ([INCREMENT]OFV -12.820). Including the full age spectrum equation, an eGFR equation based on both creatinine and CysC, led to the largest OFV reduction (-22.913); female sex was also a significant covariate of CL in the model. Final model pharmacokinetic indices were CL = 0.29 L/hr/kg and volume of distribution = 0.48 L/kg.

CONCLUSIONS: CysC-based equations help better estimate vancomycin CL than bedside Schwartz in critically ill children.

DOI10.1097/FTD.0000000000000796
Alternate JournalTher Drug Monit
PubMed ID32947559