Impact of Area Under the Concentration–Time Curve–Based Vancomycin Dosing on Efficacy and Safety in Patients With Methicillin-Resistant Staphylococcus aureus Bacteremia

Abstract

Background: The optimal strategy for dosing and monitoring vancomycin continues to evolve. A vancomycin 24-h steady-state area under the concentration–time curve/minimum inhibitory concentration (AUC/MIC) of ≥ 400 has been associated with positive clinical outcomes, while an AUC/MIC > 600–700 has been associated with increased risk of nephrotoxicity. The 2009 vancomycin dosing guidelines recommended target trough concentrations between 10–20 mcg/mL depending on infection; however, recent pharmacokinetic data suggest that most patients can achieve target AUC/MIC with trough concentrations < 15 mcg/mL. While existing literature has demonstrated reduced nephrotoxicity with AUC-guided dosing (AGD), there are limited data evaluating efficacy and other clinical outcomes. Therefore, this study compared the clinical efficacy of vancomycin using trough-guided dosing (TGD) versus AGD in patients with confirmed methicillin-resistant Staphylococcus aureus (MRSA) bacteremia.

Methods: This was a retrospective, observational, quasiexperimental study of adult patients who received vancomycin for treatment of MRSA bacteremia. Patients with central nervous system infections, weighing > 200 kg, with acute kidney injury, or receiving hemodialysis/continuous renal replacement therapy were excluded. The primary outcome was microbiological success defined as negative blood cultures within 7 days of vancomycin initiation. Secondary outcomes included achievement of therapeutic target concentrations and incidence of nephrotoxicity.

Results: Microbiological success was achieved in 52/55 (95%) patients with TGD versus 50/51 (98%) patients with AGD (p = 0.619). In the TGD group, 24/55 (44%) patients achieved therapeutic target concentrations within 48 h of initiation of vancomycin compared to 24/51 (47%) patients in the AGD group (p = 0.723). The median hospital length of stay was longer in the TGD group compared to the AGD group (16 days, IQR 11–27 days versus 13 days, IQR 9–24 days, respectively, p = 0.260). Nephrotoxicity occurred in 7/55 (13%) TGD patients versus 5/51 (10%) AGD patients during vancomycin therapy (p = 0.763).

Conclusions: AGD was similar to TGD at achieving microbiological success in patients with MRSA bacteremia and may lead to shorter lengths of hospital stay and lower rates of nephrotoxicity.