Vancomycin Trough Concentration as a Predictor of Clinical Outcomes in Patients withStaphylococcus aureusBacteremia: A Meta-analysis of Observational Studies

Abstract

Vancomycin trough concentrations do not have sufficient evidence to support their use as the primary guide in vancomycin dosing. Dosing should instead focus on AUC:MIC values, which have strong evidence of benefit.

Establishment of an AUC 0–24 Threshold for Nephrotoxicity Is a Step towards Individualized Vancomycin Dosing for Methicillin-Resistant Staphylococcus aureus Bacteremia

“…However, current dosing regimens and targets (vancomycin trough concentrations) are an area of great controversy with respect to efficacy. This is partly because of evidence showing a poor correlation between established pharmacodynamic (AUC 0 -24 ) target attainment and measured trough concentrations (6,8). Similar to others, a substantial number of our patients achieved an AUC 0 -24 of Ͼ400 despite having vancomycin trough concentrations below guideline recommendations (Յ15 mg/liter) (6).…”

“…The consequence of underexposure is treatment failure, while overexposure may lead to increased toxicity, especially acute kidney injury (AKI) (7,8).…”

Impact of Vancomycin MIC on Treatment Outcomes in Invasive Staphylococcus aureus Infections

“…Also, most previous studies of the relationship between mortality and VAN-MIC also provided only limited information pertaining to vancomycin concentration profiles. Moreover, a recent meta-analysis of observational studies reported that higher vancomycin trough concentration was not associated with reduced treatment failure and mortality (24). Thus, missing vancomycin concentrations minimally affected the conclusion of our study.…”

Commentary: Identification of Low-Level Vancomycin Resistance in Staphylococcus aureus in the Era of Informatics

“…Current evidence indicates that clinical success may be reasonably expected if the AUC/MIC ratio exceeds 400 (5,6). For patients with normal renal function, this target could not be achieved for MRSA isolates exhibiting a vancomycin MIC of Ն2 g/ml without exposing the patients to toxic levels of vancomycin (5)(6)(7).…”

“…Current evidence indicates that clinical success may be reasonably expected if the AUC/MIC ratio exceeds 400 (5,6). For patients with normal renal function, this target could not be achieved for MRSA isolates exhibiting a vancomycin MIC of Ն2 g/ml without exposing the patients to toxic levels of vancomycin (5)(6)(7). Most MRSA strains exhibit MICs of 1 g/ml, and several large surveys place 2 g/ml precisely on the border of the wild-type MIC distribution for MRSA versus vancomycin (8)(9)(10).…”