Cystatin C-Guided Vancomycin Dosing in Critically Ill Patients: A Quality Improvement Project

Abstract

Background: The aim of the study was to determine whether a vancomycin dosing algorithm based on estimated glomerular filtration rate from creatinine and cystatin C levels (eGFR_cr-cys) improves target trough concentration achievement compared to an algorithm based on estimated creatinine clearance (eCL_cr) in critically ill patients.

Study design: This prospective quality improvement project evaluated intensive care unit (ICU) patients started on intravenous vancomycin using one of 2 different strategies. Dosing regimens were selected and implemented after an individualized goal trough range was established (10-15 or 15-20mg/L). Steady-state goal trough achievement was compared between treatment arms with and without adjustment for potential confounders.

Setting & participants: 3 medical and surgical ICUs at a single tertiary medical center.

Quality improvement plan: During January 2012 to October 2013, vancomycin was dosed according to eCL_cr using the Cockcroft-Gault formula (control arm). During December 2013 to May 2015, a multidisciplinary quality improvement team implemented a novel vancomycin dosing algorithm according to eGFR_cr-cys using the CKD-EPI equation (intervention arm).

Outcome: Steady-state initial goal vancomycin trough concentration achievement.

Measurements & results: More patients in the intervention arm (67 of 135 [50%]) achieved therapeutic trough vancomycin levels than in the control arm (74 of 264 [28%]; OR, 2.53; 95% CI, 1.65-3.90; P<0.001). Improved trough achievement was maintained even after adjustment for age, sex, APACHE (Acute Physiology and Chronic Health Evaluation) III score, fluid balance, baseline CL_cr, surgical admission diagnosis, presence of sepsis, and goal trough concentration range (adjusted OR, 2.79; 95% CI, 1.76-4.44; P<0.001). Clinical outcomes were similar between groups.

Limitations: Nonrandomized, incomplete algorithm compliance.

Conclusions: A vancomycin dosing nomogram based on eGFR_cr-cys significantly improved goal trough achievement compared to eCL_cr among ICU patients with stable kidney function. Further studies are warranted to characterize the relationship between use of cystatin C-guided dosing and clinical outcomes.

Keywords: Vancomycin; antimicrobial dose regimen; creatinine; critically ill patients; cystatin C; dosing algorithm; estimated glomerular filtration rate (eGFR); goal trough concentration; intensive care unit (ICU); methicillin-resistant Staphylococcus aureus (MRSA); pharmacokinetics; quality improvement project; renal function; sepsis.