Individualized Pharmacokinetic Dosing of Vancomycin Reduces Time to Therapeutic Trough Concentrations in Critically Ill Patients

Abstract

Dosing vancomycin in critically ill patients often results in subtherapeutic and supratherapeutic trough concentrations. In this retrospective study, we compared the time to goal trough attainment and incidence of acute kidney injury in intensive care unit (ICU) patients whose vancomycin was dosed by a pharmacy pharmacokinetic (PK) dosing and monitoring service to the standard of care. Three-hundred fifty adult ICU patients at a Level 1 trauma, teaching hospital who received vancomycin for >24 hours from February 1, 2016, to November 30, 2016, were screened. Patients were included in the PK group if consecutive serum concentrations were used to calculate individualized PK and determine a dosing regimen. Patients who were dosed using troughs only were then matched 1-to-1 to the PK group by date of vancomycin initiation and included in the traditional group. Fifty patients were included in each group. Baseline characteristics were similar, except the PK group had more patients under the care of the neuromedical ICU service (42% vs 18%; P = .02) and fewer patients with a corrected creatinine clearance <30 mL/min/1.73 m (22% vs 46%; P = .02). Attainment of goal trough concentrations for the PK and traditional groups were 84.4% and 29.4% by 48 hours (P = .0001), 88.4% and 60.7% by 72 hours (P = .009), and 92.9% and 77.8% by 96 hours (P = .1), respectively. Incidence of acute kidney injury between the PK and traditional groups was not statistically significant (8.3% vs 14%; P = .5). Utilization of individualized pharmacokinetic dosing of vancomycin in critically ill patients resulted in faster goal trough attainment without an increase in nephrotoxicity.

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

“…8,9 In a study of critically ill adults, using patient-specific pharmacokinetic parameters derived from two serum concentrations after the first dose of vancomycin resulted in greater goal trough concentrations compared with patients dosed without first-dose pharmacokinetic monitoring. 9 Conversely, in pediatric patients, first-dose monitoring of vancomycin did not significantly shorten the time to achieve target serum drug concentrations. 8 Notably, these prior studies used trough levels as target attainment, which limits application to some extent in the era of vancomycin AUC-guided dosing.…”

“…The use of firstdose kinetics to guide dosing and the subsequent impact on vancomycin trough attainment has demonstrated mixed results in prior studies. 8,9 The availability of both dosing approaches at our institution allowed a unique opportunity to compare dosing strategies of vancomycin on AUC target attainment in critically ill adults.…”

Model‐Informed Artificial Intelligence: Reinforcement Learning for Precision Dosing

“…9 In a few cases, such as effective use of some antimicrobial agents in life-threatening infections where rapid attainment of appropriate drug exposures is required, PK/PD models are used to guide dosing. 10 See also ref. 11 as an example of dose optimization of therapeutic antibodies.…”

The Importance of Individualized Vancomycin Dosing to Ensure Optimal Exposure Early in Therapy

“…We read with great interest the article by Truong et al evaluating the ability of a patient‐specific pharmacokinetic approach to achieve rapid attainment of vancomycin pharmacokinetic/pharmacodynamic targets in critically ill patients . Using an institutional protocol that utilized a standardized, weight‐based vancomycin loading dose followed directly by 2 serum concentrations drawn within the same dose interval to derive a maintenance dose, they demonstrated a higher probability of target trough attainment and faster time to trough target attainment relative to the institutional standard‐of‐care approach.…”

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We read with great interest the article by Truong et al evaluating the ability of a patient-specific pharmacokinetic approach to achieve rapid attainment of vancomycin pharmacokinetic/pharmacodynamic targets in critically ill patients. 1 Using an institutional protocol that utilized a standardized, weight-based vancomycin loading dose followed directly by 2 serum concentrations drawn within the same dose interval to derive a maintenance dose, they demonstrated a higher probability of target trough attainment and faster time to trough target attainment relative to the institutional standard-of-care approach. Standard care at the institution was consistent with current vancomycin therapeutic monitoring guideline recommendations, which included optional weight-based loading doses, weightand creatinine clearance-based maintenance doses, and trough concentrations drawn before the third or fourth dose for potential dose adjustment.

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