Is Early Monitoring Better? Impact of Early Vancomycin Exposure on Treatment Outcomes and Nephrotoxicity in Patients with Methicillin-Resistant <i>Staphylococcus aureus</i> Infections

Abstract

Optimal early vancomycin target exposure remains controversial. To clarify the therapeutic exposure range, we investigated the association between vancomycin exposure and treatment outcomes or nephrotoxicity in patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. This retrospective study reviewed clinical data obtained from 131 patients with MRSA infections between January 2017 and September 2019. Clinical outcomes included treatment failure, 30-day mortality, microbiological failure, and acute kidney injury. We measured serum vancomycin levels after the first dose to 48 h and estimated vancomycin exposure using the Bayesian theorem. The minimum inhibitory concentration (MIC) of antimicrobial agents was determined using the broth microdilution method. Classification and Regression Tree analyses identified day 1 and 2 exposure thresholds associated with an increased risk of failure and nephrotoxicity. Treatment failure (27.9% vs. 33.3%) and 30-day mortality (26.6% vs. 31.74%) were numerically but not significantly reduced in patients with the area under the curve (AUC)24–48h/MICBMD ≥ 698. Patients with AUCss/MICBMD ≥ 679 exhibited a significantly increased risk of acute kidney injury (27.9% vs. 10.9%, p = 0.041). These findings indicate that AUCss/MICBMD ratios > 600 may cause nephrotoxicity. AUC/MICBMD at days 1 and 2 do not appear to be significantly associated with particular clinical outcomes, but further studies are needed.

Keywords

• area under the curve
• mortality
• MRSA
• nephrotoxicity
• vancomycin