Dosing vancomycin in the super obese: less is more

Crass, Ryan L.; Dunn, Ryan; Hong, Joseph; Krop, Lynne C; Pai, Manjunath P.

doi:10.1093/jac/dky310

Cited by 41 publications

(41 citation statements)

References 17 publications

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“…Our results on vancomycin clearance and volume of distribution in obese individuals puts forward what was known on vancomycin PK in obesity. Regarding clearance, predominantly retrospective studies also found a larger vancomycin clearance in obese compared to nonobese individuals . One prospective rich sampling PK study in healthy obese individuals, similar to our study design but with only 6 obese individuals included, found a linear relationship of TBW with vancomycin clearance, in contrast to the power relationship as found in our study .…”

Section: Discussionsupporting

confidence: 67%

“…This might be explained by the relatively low body weight in the obese group (mean TBW 94.3 kg). Other reports in which obese patients were included, show conflicting results on the best predictive covariate for vancomycin clearance, varying from CG with TBW, serum creatinine, or a combination of serum creatinine, age, TBW and sex . These results might be explained by differences in studied body weights or employed sampling schedules (i.e.…”

Section: Discussionmentioning

confidence: 97%

“…A strong aspect of our study is the prospective study design with intensive PK sampling in adults with a wide range of body weights across the included cohort from 60 to 235 kg, allowing for the characterisation of a 3‐compartment model. This is in contrast with other reports on vancomycin PK in obesity, that fully rely on TDM data, that consist mostly of peak and trough concentrations, making it difficult to estimate >1 compartment, thereby limiting the ability to adequately assess individual PK parameters . Moreover, we used data from a previously performed study to externally validate our model .…”

Section: Discussionmentioning

confidence: 99%

“…Initially, total body weight (TBW) was shown to be the best predictor for vancomycin clearance . However, these findings have been challenged by other studies conducted in obese patients, including the most recent …”

Section: Introductionmentioning

confidence: 99%

“…18 Since the FDA-regimen has been shown to result in suboptimal exposure (AUC 24h around 100-250 mg h L −1 ) in normal weight adults, more recent guidelines recommend 15-20 mg kg −1 every 8-12 h. 13 This rather broad dosing regimen is also recommended for obese patients, thereby resulting in a large variability of dose regimens used for obese individuals in clinical practice 13 and is based on studies that are mostly performed with sparse data based on routine therapeutic drug monitoring (TDM) peak and trough levels. [19][20][21][22][23][24] Most of these studies show that both volume of distribution and clearance increase in obese patients. Initially, total body weight (TBW) was shown to be the best predictor for vancomycin clearance.…”

Section: Introductionmentioning

confidence: 99%

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Population pharmacokinetics of vancomycin in obesity: Finding the optimal dose for (morbidly) obese individuals

Smit

Wasmann

Goulooze

et al. 2020

Brit J Clinical Pharma

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Aims For vancomycin treatment in obese patients, there is no consensus on the optimal dose that will lead to the pharmacodynamic target (area under the curve 400–700 mg h L−1). This prospective study quantifies vancomycin pharmacokinetics in morbidly obese and nonobese individuals, in order to guide vancomycin dosing in the obese. Methods Morbidly obese individuals (n = 20) undergoing bariatric surgery and nonobese healthy volunteers (n = 8; total body weight [TBW] 60.0–234.6 kg) received a single vancomycin dose (obese: 12.5 mg kg−1, maximum 2500 mg; nonobese: 1000 mg) with plasma concentrations measured over 48 h (11–13 samples per individual). Modelling, internal validation, external validation using previously published data and simulations (n = 10.000 individuals, TBW 60–230 kg) were performed using NONMEM. Results In a 3‐compartment model, peripheral volume of distribution and clearance increased with TBW (both p < 0.001), which was confirmed in the external validation. A dose of 35 mg kg−1 day−1 (maximum 5500 mg/day) resulted in a > 90% target attainment (area under the curve > 400 mg h L−1) in individuals up to 200 kg, with corresponding trough concentrations of 5.7–14.6 mg L−1 (twice daily dosing). For continuous infusion, a loading dose of 1500 mg is required for steady state on day 1. Conclusion In this prospective, rich sampling pharmacokinetic study, vancomycin clearance was well predicted using TBW. We recommend that in obese individuals without renal impairment, vancomycin should be dosed as 35 mg kg−1 day−1 (maximized at 5500 mg/day). When given over 2 daily doses, trough concentrations of 5.7–14.6 mg L−1 correspond to the target exposure in obese individuals.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Population pharmacokinetics of vancomycin in obesity: Finding the optimal dose for (morbidly) obese individuals

Smit

Wasmann

Goulooze

et al. 2020

Brit J Clinical Pharma

View full text Add to dashboard Cite

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External Validation of Obese/Critically Ill Vancomycin Population Pharmacokinetic Models in Critically Ill Patients Who Are Obese

Alsultan,

Dasuqi,

Almohaizeie

et al. 2023

The Journal of Clinical Pharma

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Obesity combined with critical illness might increase the risk of acquiring infections and hence mortality. In this patient population antimicrobials pharmacokinetics vary significantly making antimicrobial dosing challenging. The objective of this study was to assess the predictive performance of published population pharmacokinetic models of vancomycin in critically ill or obese patients on a cohort of critically ill obese patients. This was a multi‐center retrospective study conducted at two hospitals. Adult patients with a BMI ≥ 30 were included. PubMed was searched for published population pharmacokinetic studies in critically ill or obese patients. External validation was performed using Monolix software. Four models were identified in obese patients and 5 models in critically ill patients. In total, 138 critically ill obese patients were included, the most accurate models for patients were the Goti and Roberts models. In our analysis, models in critically ill patients outperformed those in obese patients. When looking at the most accurate models, both (the Goti and Roberts models) had patient characteristics similar to ours in terms of age and creatinine clearance. This indicates that when selecting the proper model to apply in practice, it is important to account for all relevant variables besides obesity.This article is protected by copyright. All rights reserved

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Conversion from Vancomycin Trough Concentration–Guided Dosing to Area Under the Curve–Guided Dosing Using Two Sample Measurements in Adults: Implementation at an Academic Medical Center

et al. 2019

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STUDY OBJECTIVE The optimal pharmacodynamic parameter for the prediction of efficacy of vancomycin is the area under the concentration-time curve (AUC), and current published data indicate that dosing based on vancomycin trough concentrations is an inaccurate substitute. In this study, our objective was to compare the achievement of therapeutic target attainment after switching from a trough-based to an AUC-based dosing strategy as a part of our institution's vancomycin-per-pharmacy protocol. DESIGN Prospective observational quality assurance study. SETTING Academic medical center. PATIENTS A total of 296 hospitalized adults who received vancomycin and monitoring under our institution's vancomycin-per-pharmacy protocol were included in the analysis. The preimplementation retrospective comparison group consisted of 179 patients in whom vancomycin was initiated using a trough-based dosing strategy between November 22, 2017, and January 22, 2018. The postimplementation group included 117 patients in whom vancomycin was initiated using an AUC-based dosing strategy using two-point sampling between June 19, 2018, and July 19, 2018, after hospital-wide implementation of this protocol on June 19, 2018. MEASUREMENTS AND MAIN RESULTS AUC values were calculated from two vancomycin concentrations (peak and trough). The primary outcome was achievement of therapeutic AUC values (400-800 mgÁhr/L) in the postimplementation group or therapeutic trough level values (10-20 mg/L) in the preimplementation group. Only 98 (55%) of 179 initial trough values were therapeutic in the preimplementation group (trough-only dosing method) versus 86 (73.5%) of 117 initial AUC values in the postimplementation group (AUC-based dosing method) (p=0.0014). A lower proportion of supratherapeutic AUC values was observed in the postimplementation group compared with supratherapeutic trough concentrations in the preimplementation group (1.7% vs 18%, p<0.0001). Overall, 62% of patients with initially therapeutic AUC values had subsequent trough value increases of 25% or greater, occurring at a median of 6 days of vancomycin therapy. Nephrotoxicity occurred in 11% of patients in the preimplementation versus 9.4% in the postimplementation group (p=0.70). CONCLUSION Compared with a trough concentration-based dosing strategy, AUC-based dosing using two-point sampling improved therapeutic target attainment. Implementation is feasible at any hospital that performs vancomycin peak concentration testing and is a workable alternative to using Bayesian software for estimating AUC. This approach should also be directly compared with AUC-based dosing using Bayesian software.

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Dosing vancomycin in the super obese: less is more

Abstract: Empirical vancomycin dosing informed by common clinical variables, including standardized creatinine, with subsequent individualization using AUC-targeted TDM can optimize therapy in obese and super obese adults.

Cited by 41 publications

References 17 publications

Population pharmacokinetics of vancomycin in obesity: Finding the optimal dose for (morbidly) obese individuals

Population pharmacokinetics of vancomycin in obesity: Finding the optimal dose for (morbidly) obese individuals

External Validation of Obese/Critically Ill Vancomycin Population Pharmacokinetic Models in Critically Ill Patients Who Are Obese

Conversion from Vancomycin Trough Concentration–Guided Dosing to Area Under the Curve–Guided Dosing Using Two Sample Measurements in Adults: Implementation at an Academic Medical Center

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