First‐Dose Vancomycin Pharmacokinetics Versus Empiric Dosing on Area‐Under‐the‐Curve Target Attainment in Critically Ill Patients

Flannery, Alexander H.; Delozier, Natalie L.; Effoe, S. Aaron; Wallace, Katie; Cook, Aaron M.; Burgess, David S.

doi:10.1002/phar.2486

Cited by 11 publications

(9 citation statements)

References 24 publications

(55 reference statements)

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“…Several published reports suggested that vancomycin exhibits longer distribution phase [ 17 , 60 , 61 ] and using one compartment approach may result in inaccurate PK estimations. Flannery et al [ 21 ] reported that PTA at steady state was 58.6% with one compartment approach, which is also in accordance with observations from Ackerman et al [ 62 ], suggesting that the one-compartment model may not be sufficient to predict vancomycin exposure.…”

Section: Discussionsupporting

confidence: 69%

“…Method 3 is an adopted approach from Flannery et al [ 21 ], which recommends collecting two samples. One sample at 2.5 h (1–2 h after the end of infusion), and the other level at 11.5 h (trough level) are collected.…”

Section: Discussionmentioning

confidence: 99%

“…According to the method described by Flannery et al [ 21 ], the concentration-time profiles of simulated patients were assumed to fit a one-compartment model. Two concentrations of each subject, i.e., levels at t 1 (2.5 h) and t 2 (11.5 h) after the first dose, were used to calculate the AUC 0–∞ ( Figure 1 ).…”

Section: Methodsmentioning

confidence: 99%

“…To adjust vancomycin dosing at an early time, researchers ventured to calculate the personalized PK parameters using two vancomycin concentrations sampled after the first dose and guide the subsequent dosing regimen [ 21 ]. However, AUC estimated using parameters based on the one-compartment model is not plausible.…”

Section: Introductionmentioning

confidence: 99%

“…The PK profiles of 1000 virtual patients with normal renal function generated from a well-established pop PK model using Monte Carlo simulation were used to validate the feasibility of the proposed approaches. The predictive accuracy is compared with that of the previous reported methodology [ 21 ]. Furthermore, the proposed methodologies were also tested in virtual patients with different levels of renal impairment.…”

Section: Introductionmentioning

confidence: 99%

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Two Innovative Approaches to Optimize Vancomycin Dosing Using Estimated AUC after First Dose: Validation Using Data Generated from Population PK Model Coupled with Monte-Carlo Simulation and Comparison with the First-Order PK Equation Approach

Liu

Huang

et al. 2022

Pharmaceutics

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The revised consensus guidelines for optimizing vancomycin doses suggest that maintaining the area under the concentration-time curve to minimal inhibitory concentration ratio (AUC/MIC) of 400–600 mg·h/L is the target pharmacokinetic/pharmacodynamic (PK/PD) index for efficacy. AUC-guided dosing approach uses a first-order pharmacokinetics (PK) equation to estimate AUC using two samples obtained at steady state and one-compartment model, which can cause inaccurate AUC estimation and fail to achieve the effective PK/PD target early in therapy (days 1 and 2). To achieve an efficacy target from the third or fourth dose, two innovative approaches (Method 1 and Method 2) to estimate vancomycin AUC at steady state (AUCSS) using two-compartment model and three or four levels after the first dose are proposed. The feasibility of the proposed methods was evaluated and compared with another published dosing algorithm (Method 3), which uses two samples and a one-compartment approach. Monte Carlo simulation was performed using a well-established population PK model, and concentration-time profiles for virtual patients with various degrees of renal function were generated, with 1000 subjects per group. AUC extrapolated to infinity (AUC0–∞) after the first dose was estimated using the three methods, whereas reference AUC (AUCref) was calculated using the linear-trapezoidal method at steady state after repeated doses. The ratio of AUC0–∞: AUCref and % bias were selected as the indicators to evaluate the accuracy of three methods. Sensitivity analysis was performed to examine the influence of change in each sampling time on the estimated AUC0–∞ using the two proposed approaches. For simulated patients with various creatinine clearance, the mean of AUC0–∞: AUCref obtained from Method 1, Method 2 and Method 3 ranged between 0.98 to 1, 0.96 to 0.99, and 0.44 to 0.69, respectively. The mean bias observed with the three methods was −0.10% to −2.09%, −1.30% to −3.59% and −30.75% to −55.53%, respectively. The largest mean bias observed by changing sampling time while using Method 1 and Method 2 were −4.30% and −10.50%, respectively. Three user-friendly and easy-to-use excel calculators were built based on the two proposed methods. The results showed that our approaches ensured sufficient accuracy and achieved target PK/PD index early and were superior to the published methodologies. Our methodology has the potential to be used for vancomycin dose optimization and can be easily implemented in clinical practice.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Two Innovative Approaches to Optimize Vancomycin Dosing Using Estimated AUC after First Dose: Validation Using Data Generated from Population PK Model Coupled with Monte-Carlo Simulation and Comparison with the First-Order PK Equation Approach

Liu

Huang

et al. 2022

Pharmaceutics

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Characterizing Day 1 Area Under the Curve Following Vancomycin Loading Dose Administration in Adult Hospitalized Patients Using Non-Trapezoidal Linear Pharmacokinetic Equations: A Retrospective Observational Study

Shremo Msdi,

Abdul-Mutakabbir,

Tan

2024

Infect Dis Ther

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Introduction Methicillin-resistant Staphylococcus aureus (MRSA) infections are a serious threat to public health. Vancomycin (VAN) remains the primary treatment for these infections, and achieving the recommended area under the curve (AUC) target has been linked to improved clinical outcomes. The current VAN therapeutic monitoring guidelines recommend a loading dose (LD) of 20–35 mg/kg to rapidly attain targeted VAN exposures within 24 h of therapy. However, there is a paucity of data describing the impact of VAN LD on day 1 area under the curve (AUC 0–24 ). This study aims to employ pharmacokinetic (PK) equations to calculate and describe the AUC 0–24 following a VAN LD of 20 mg/kg. Methods This was a retrospective study of adult patients who were loaded with VAN 20 mg/kg, received ≥ 48 h of treatment, and had two consecutive serum VAN levels collected within 24 h. Linear, non-trapezoidal PK equations and two post-infusion VAN levels were used to calculate AUC 0–24 . Therapeutic AUC 0–24 was defined as 400–600 mg/l*h. Results Among 123 included patients, the median age was 46 years (IQR 36, 62), 54% (67/123) of the patients had a body mass index (BMI) ≥ 30 kg/m 2 and 27% (33/123) were admitted to the intensive care unit (ICU). Following a LD of 20 mg/kg, 50% (61/123) of the patients met the therapeutic AUC 0–24 , while 22% (27/123) of the patients were subtherapeutic, and 28% (35/123) were supratherapeutic. Compared with patients who achieved therapeutic AUC 0–24 , patients with subtherapeutic AUC 0–24 were more likely to be younger (44 vs. 37 years old) and have a BMI ≥ 30 kg/m 2 (67 vs. 52%). In contrast, patients with supratherapeutic AUC 0–24 were more likely to be older (64 vs. 44 years old) and to have chronic kidney disease diagnosis (23 vs. 7%) when compared to patients who achieved a therapeutic AUC 0–24. Conclusions Only 50% of patients achieve the target AUC 0-24 following a VAN 20 mg/kg LD, with younger, heavier patients underexposed and older patients with renal impairment overexposed, suggesting that different dosing strategies are needed for these populations. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-024-01004-2.

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Glycopeptide and Lipoglycopeptide Antibiotics

Tonna

2022

Comprehensive Pharmacology

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First‐Dose Vancomycin Pharmacokinetics Versus Empiric Dosing on Area‐Under‐the‐Curve Target Attainment in Critically Ill Patients

Cited by 11 publications

References 24 publications

Two Innovative Approaches to Optimize Vancomycin Dosing Using Estimated AUC after First Dose: Validation Using Data Generated from Population PK Model Coupled with Monte-Carlo Simulation and Comparison with the First-Order PK Equation Approach

Two Innovative Approaches to Optimize Vancomycin Dosing Using Estimated AUC after First Dose: Validation Using Data Generated from Population PK Model Coupled with Monte-Carlo Simulation and Comparison with the First-Order PK Equation Approach

Characterizing Day 1 Area Under the Curve Following Vancomycin Loading Dose Administration in Adult Hospitalized Patients Using Non-Trapezoidal Linear Pharmacokinetic Equations: A Retrospective Observational Study

Glycopeptide and Lipoglycopeptide Antibiotics

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