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

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 &gt; 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 &lt; 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 &gt; 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.