Use of Cystatin C-Based Renal Function Estimation for Empiric Antimicrobial Dosing

Introduction: Creatinine clearance (CrCl) is the primary method to estimate medication clearance and make dose adjustments. Recent evidence suggests estimated glomerular filtration rate (eGFR) incorporating cystatin C (cysC), may more accurately estimate medication clearance.


Description: 57-year-old male with history of quadriplegia and neurogenic bladder was transferred to the intensive care unit for possible septic shock. Vasoactive infusions were initiated following 30 mL/kg of Plasmalyte-A to achieve hemodynamic targets (MAP ≥ 65 mmHg). Intravenous (IV) cefepime, metronidazole and vancomycin were ordered. The last serum creatinine (Scr) was 0.23 equating to CrCl 364 mL/min and eGFR 150 mL/min/1.73 m2. Considering the patient’s history and 24-hour documented urinary catheter output 0.29 mL/kg/hr, there was concern the CrCl may be misleading, and a cystatin C (cysC) was ordered with new labs and blood cultures. New labs were Scr 0.23 mg/dL and cysC 0.93 mg/L. Based on the Scr and/or cysC, indexed (i) and non-indexed (ni) eGFRs using 2012 and 2021 Chronic Kidney Disease Epidemiology Collaboration equations were calculated. Both Scr and cysC resulted in an eGFR(i) 117 mL/min/1.73 m2 or eGFR(ni) of 131 mL/min. Using only cysC resulted in an eGFR(i) 87 mL/min/1.73 m2 or eGFR(ni) of 97 mL/min. For assumed muscle mass changes due to quadriplegia, eGFR(ni)-cysC was used. Based on an internal protocol, the patient was started on vancomycin 1250 mg IV every 12 hours, after a loading dose, instead of every eight hours if CrCl was used. Cefepime regimen 2000 mg IV every 8 hours was initiated. The steady-state vancomycin trough was 20.8 micrograms (mcg)/mL and the vancomycin dose was reduced from 1250 mg to 1000 mg to achieve a goal trough of 15-20 mcg/mL. Based on two cefepime levels, the free minimum concentration (fCmin) was 10.06 mcg/mL. The institutional fCmin target is greater than or equal to 4x the minimum inhibitory concentration (MIC). This fCmin achieved 4xMIC and 259.03% time over MIC, assuming a MIC of 2.


Discussion: Creatinine-alone estimations of renal clearance have known limitations and are unreliable for medication dose adjustments. CysC use is not routine practice for medication initiation; however, cysC may aid with drug dosing decisions in addition to therapeutic drug monitoring.