Evaluation of the Effectiveness of Dose Individualization to Achieve Therapeutic Vancomycin Concentrations

Abstract

The glycopeptide antibiotic vancomycin is used for treatment of methicillin-resistant Gram-positive cocci. Adequate vancomycin plasma concentrations are related to bacterial cure. However, inter- and intrapatient variability make it difficult to achieve therapeutic vancomycin concentrations. The primary objective of this study was to determine the effectiveness of using computerized therapeutic drug monitoring (TDM) to assist in achieving therapeutic vancomycin concentrations at a tertiary hospital in South Africa. This was a 2-period study consisting of a retrospective 1-month observational period followed by a prospective 1-month period in which computerized TDM was implemented as an intervention to assist with vancomycin dose individualization. During the prospective period, all vancomycin TDM results were followed by dosage individualization using computerized TDM. The retrospective period included 77 patients with 292 vancomycin concentrations: 69% (53/77) adult and 31% (24/77) pediatric patients. The prospective period included 80 patients with 217 vancomycin concentrations measured: 69% (55/80) adult and 31% (25/80) pediatric patients. Fewer vancomycin TDM data were requested during the prospective period with a median (interquartile range) of 2 (1-3) samples per patient compared with 3 (1-5) samples per patient during the retrospective period. The odds ratio of achieving therapeutic trough concentrations was 3.63 (95%CI 1.81-7.3) in the prospective period when TDM-adjusted vancomycin dosing and appropriate TDM procedures were applied. The use of computerized TDM resulted in a higher frequency of therapeutic vancomycin concentrations in a middle-income setting. Trough vancomycin concentrations alone correlate poorly with the area under plasma concentration-time curve from 0 to 24 hours.

Model-Informed Precision Dosing of Vancomycin in Hospitalized Children: Implementation and Adoption at an Academic Children’s Hospital

“…The calculations for AUC 24 /MIC can be difficult to perform in the context of clinical workflow, and the trough concentration is often used as a surrogate in clinical care instead. However, the correlation between trough and AUC 24 are imprecise (Frymoyer et al, 2014;Stockmann et al, 2015;Abulfathi et al, 2018) and dose individualization to optimize the AUC 24 /MIC during clinical care are now recommended. MIPD will allow providers to easily calculate and implement A U C 2 4 / M I C e x p o s u r e a s s e s s m e n t i n t h e r a p e u t i c decision making.…”

“…The framework and potential clinical utility of such a model-informed precision dosing (MIPD) approach has been well-described (Sheiner and Beal, 1982;Barrett, 2015;Mould et al, 2016;Darwich et al, 2017;Gonzalez et al, 2017;Neely, 2017). Despite the potential advantages and the recent availability of several MIPD software platforms (Turner et al, 2018), the implementation of MIPD in clinical care has been limited to date (van Lent-Evers et al, 1999;Álvarez-Romań et al, 2017>;Abulfathi et al, 2018;Neely et al, 2018;McGann et al, 2019).…”

An Evaluation of Vancomycin Area Under the Curve Estimation Methods for Children Treated for Acute Pulmonary Exacerbations of Cystic Fibrosis Due to Methicillin‐Resistant Staphylococcus aureus

“…10 However, it is widely appreciated that a single trough concentration does not perfectly correlate with the AUC, with r 2 values reported to be approximately 0.6. [34][35][36] This was the driving motivation for the current study, which sought to test whether a reference AUC (derived with a population pharmacokinetic model fitted to both a postdistributive concentration and a trough concentration) could be closely approximated using alternative AUC estimation methods. As described by Neely et al in a cohort of adults, the use of a population pharmacokinetic model (fitted with both a postdistributive concentration and a trough concentration) as a prior resulted in unbiased and precise AUC estimates when applied to a data set comprised solely of trough concentrations.…”

“…Due to the requirement to obtain 2 concentrations to precisely measure the AUC, guidelines from the Infectious Diseases Society of America and the Pediatric Infectious Diseases Society suggest that using a trough concentration only is a practical means of performing vancomycin therapeutic drug monitoring . However, it is widely appreciated that a single trough concentration does not perfectly correlate with the AUC, with r 2 values reported to be approximately 0.6 . This was the driving motivation for the current study, which sought to test whether a reference AUC (derived with a population pharmacokinetic model fitted to both a postdistributive concentration and a trough concentration) could be closely approximated using alternative AUC estimation methods.…”

Report of Three Cases of AKI Following Weight-Based Gentamicin Prophylaxis for IPP Implantation: Potential Concerns for Patients with Preexisting Conditions

“…The antibacterial effect of vancomycin is based on time-dependent exposure as measured by the ratio of the 24-hour area under the concentration-time curve (AUC) to the MIC. Although trough levels are typically used as a surrogate for this measure, supratherapeutic concentrations may result in nephrotoxicity [5]. However, the influence of vancomycin on AKI could not be fully assessed due to the lack of measured serum levels.…”