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

Impact of Cystatin-C C-guided Vancomycin Dosing Recommendation on Target Trough Achievement and Clinical Outcomes in Critically Ill Adults

Determine if a cystatin C-inclusive vancomycin dosing algorithm improved target trough achievement compared to creatinine clearance-guided vancomycin therapy in critically ill patients.

This is a prospective, quality improvement study that evaluated critically ill patients initiated on intravenous vancomycin. Between January 2012 through October 2013, vancomycin was dosed at 15-20mg/kg at an interval guided by creatinine clearance using the Cockcroft Gault equation (control arm). Steady state trough concentrations were assessed prior to the 4th dose of a consistent regimen and compared to the individualized target trough range (10-15mg/L or 15-20mg/L) appropriate for the suspected or documented source of infection. Given low overall trough achievement observed with standard care, a quality improvement project was undertaken. After approval by local clinical practice committees with representation from the Division of Infectious Diseases, Pharmacy and Critical Care, a quality improvement project was undertaken to implement a new vancomycin dosing nomogram with dosing intervals based on the Chronic Kidney Disease Epidemiology Collaborative (CKD-EPI) creatinine-cystatin GFR equation, expressed in mL/min. After structured education was provided, the dosing algorithm was rolled out from December 2013 through May 2015 (intervention arm). Steady state target vancomycin trough achievement was compared between study arms with and without adjustment for potential confounders.

Cystatin C is an endogenous cysteine proteinase inhibitor produced by all nucleated cells and a biomarker used routinely to estimate glomerular filtration rate either alone or in combination with creatinine. This new dosing algorithm includes patient weight, individualized goal trough concentration, and glomerular filtration rate (expressed with the CKD-EPI creatinine-cystatin C equation in mL/min) to determine dose and frequency.

Historical controls for the quality improvement project had doses based on weight and interval established with the creatinine clearance using the Cockcroft-Gault equation.

New onset AKI, defined as KDIGO stage II or greater AKI, within 48-hours of and within 7-days of vancomycin initiation

Treatment failure in patients with confirmed gram-positive infection after at least 48-hours of vancomycin therapy and within 7-days

Inclusion Criteria: Hospitalized in one of three intensive care units at Mayo Clinic in Rochester, Minnesota Suspected or documented gram-positive infection Prescribed IV vancomycin at a consistent dose and scheduled with 8, 12, or 24 hour Vancomycin dosing interval Exclusion Criteria: Vulnerable population Received greater than 1 dose of Vancomycin in the 96 hours before ICU admission Baseline glomerular filtration rate (GFR) of less than 20 milliliters/minute Undergoing renal replacement therapy Body mass index > 40kg/m2 Weight < 40kg

Frazee EN, Rule AD, Herrmann SM, Kashani KB, Leung N, Virk A, Voskoboev N, Lieske JC. Serum cystatin C predicts vancomycin trough levels better than serum creatinine in hospitalized patients: a cohort study. Crit Care. 2014 May 29;18(3):R110. doi: 10.1186/cc13899.