Continuous versus intermittent vancomycin infusion in icu patients with augmented renal clearance

Introduction: Augmented renal clearance (ARC) has been associated with sub-optimal antibiotic concentrations. Administering vancomycin as a continuous infusion may be a strategy to achieve therapeutic levels faster with less monitoring. The purpose of this study was to compare the safety and efficacy of continuous infusion vancomycin (CIV) versus intermittent infusion vancomycin (IIV) in critically ill patients with ARC. Methods: This was a single-center, retrospective study of adult patients admitted to the ICU at Stanford Health Care. Patients were included if they received intravenous vancomycin and had ARC (creatinine clearance > 130 ml/min calculated by Cockroft-Gault equation). Patients were excluded if they received vancomycin for surgical prophylaxis. From January 2020 – March 2021, patients received IIV targeting a vancomycin area-under-the-curve (AUC) of 400-600 mg*h/L calculated by the trapezoidal method (using peak and trough levels). From April 2021 – March 2022, patients received CIV with a target level of 17-25 mcg/mL (representing an AUC of 408-600 mg*h/L) drawn at least 24 hours after initiation. The primary outcome was the time to achieve target levels for each dosing strategy. Secondary outcomes included the incidence of acute kidney injury (AKI) define by the RIFLE criteria and number of vancomycin levels collected. Results: Fifty-one patients were included for analysis (38 in IIV group and 13 in CIV group). Median treatment duration was 3.8 days for IIV and 3 days in the CIV group (p=0.2). Median daily dose was 34 and 44 mg/kg in the IIV and CIV group respectively (p=0.06). Median time to target level was 1.4 days in the IIV vs 1.1 days in the CIV group (p=0.26). Initial vancomycin levels were therapeutic in 42% in the IIV group vs 61% in the CIV group (p = 0.27). Incidence of AKI was 24% in for IIV vs 8% for CIV (p=0.21) despite higher total daily doses in the CIV group. Median number of levels drawn was 3 vs. 2 in the IIV and CIV groups respectively (p=0.01). Conclusions: Administration of vancomycin as a continuous infusion may be an alternative dosing strategy in critically ill patients with ARC. Given this study was underpowered, larger studies are warranted to further explore the efficacy and safety of continuous infusion vancomycin.