Balancing Vancomycin Efficacy and Nephrotoxicity: Should We Be Aiming for Trough or AUC/MIC?

Abstract

Sixty years later, the question that still remains is how to appropriately utilize vancomycin in the pediatric population. The Infectious Diseases Society of America published guidelines in 2011 that provide guidance for dosing and monitoring of vancomycin in adults and pediatrics. However, goal vancomycin trough concentrations of 15-20 μg/mL for invasive infections caused by methicillin-resistant Staphylococcus aureus were based primarily on adult pharmacokinetic and pharmacodynamic data that achieved an area under the curve to minimum inhibitory concentration ratio (AUC/MIC) of ≥400. Recent pediatric literature shows that vancomycin trough concentrations needed to achieve the target AUC/MIC are different than the adult goal troughs cited in the guidelines. This paper addresses several thoughts, including the role of vancomycin AUC/MIC in dosing strategies and safety monitoring, consistency in laboratory reporting, and future directions for calculating AUC/MIC in pediatrics.

Impact of Initial Vancomycin Trough Concentration on Clinical and Microbiological Outcomes of Methicillin-ResistantStaphylococcus aureusBacteremia in Children

“…The AUC of vancomycin is a well-known theoretical PK/PD model reflecting the effectiveness of vancomycin exposure (15). Because it is nearly impossible to measure an accurate AUC in clinical practice especially in young children, it is important to develop an appropriate PK/PD model.…”

Empirical Vancomycin Dosing in Pediatric Patients with Congenital Heart Disease and the Impact of Cardiopulmonary Bypass on Trough Concentrations

“…The primary efficacy outcome was the total daily vancomycin dose (mg/kg/day) required to achieve a therapeutic vancomycin trough concentration between 8 and 15 μg/ml . Concentrations were considered therapeutic if they fell between the range of 8–15 μg/ml because this range would not prompt dosing interventions at our institution for empirical vancomycin regimens ahead of organism identification in the CVICU without suspicion of worsening infection, concern for a difficult to penetrate site of infection (e.g., meningitis or endocarditis), and/or evidence of acute kidney injury (AKI).…”

“…The purpose of this study was to determine the optimal empirical vancomycin dosing regimen for patients with CHD to achieve goal vancomycin concentrations between 8 and 15 μg/ml …”

“…3,4 The purpose of this study was to determine the optimal empirical vancomycin dosing regimen for patients with CHD to achieve goal vancomycin concentrations between 8 and 15 lg/ ml. 5,6 We also aimed to characterize the impact of cardiopulmonary bypass (CPB) on empirical vancomycin dosing requirements in this patient population. We hypothesized that post-CPB patients would require lower doses than patients who have not been exposed to CPB because of a potential decrease in vancomycin clearance in this population.…”

Optimizing Guideline-Recommended Antibiotic Doses for Pediatric Infective Endocarditis

“…Positive outcomes with vancomycin are best predicted by achievement of an AUC:MIC of ≥400:1, which may or may not be accurately predicted by trough concentrations in children.13 Area under the curve monitoring, using 2 concentrations or Bayesian software, may be a more appropriate monitoring parameter for efficacy. 13 Although it is recognized that other dosing references may be more appropriate for in-depth discussions and drug dosing recommendations, the 2015 IE Update as written gives the impression that the contained information is sufficient for provision of care of all pediatric patients. Important additions to the vancomycin TDM risk-benefit discussion include the lack of studies in children correlating attainment of trough concentration targets with efficacy and evidence that higher trough concentrations (≥15 mg/L) may be associated with acute kidney injury.…”