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. 2021 Oct 9;10(10):1228.
doi: 10.3390/antibiotics10101228.

Population Pharmacokinetics and Dosing Simulation of Vancomycin Administered by Continuous Injection in Critically Ill Patient

Romain Garreau  1   2 , Benoît Falquet  1 , Lisa Mioux  1 , Laurent Bourguignon  1   2   3 , Tristan Ferry  3   4 , Michel Tod  1   2   3 , Florent Wallet  5 , Arnaud Friggeri  3   5   6 , Jean-Christophe Richard  3   7 , Sylvain Goutelle  1   2   3
Affiliations

Population Pharmacokinetics and Dosing Simulation of Vancomycin Administered by Continuous Injection in Critically Ill Patient

Romain Garreau et al. Antibiotics (Basel). .

Abstract

Background: Vancomycin is widely used for empirical antimicrobial therapy in critically ill patients with sepsis. Continuous infusion (CI) may provide more stable exposure than intermittent infusion, but optimal dosing remains challenging. The aims of this study were to perform population pharmacokinetic (PK) analysis of vancomycin administered by CI in intensive care unit (ICU) patients to identify optimal dosages. Methods: Patients who received vancomycin by CI with at least one measured concentration in our center over 16 months were included, including those under continuous renal replacement therapy (CRRT). Population PK was conducted and external validation of the final model was performed in a dataset from another center. Simulations were conducted with the final model to identify the optimal loading and maintenance doses for various stages of estimated creatinine clearance (CRCL) and in patients on CRRT. Target exposure was defined as daily AUC of 400-600 mg·h/L on the second day of therapy (AUC24-48 h). Results: A two-compartment model best described the data. Central volume of distribution was allometrically scaled to ideal body weight (IBW), whereas vancomycin clearance was influenced by CRRT and CRCL. Simulations performed with the final model suggested a loading dose of 27.5 mg/kg of IBW. The maintenance dose ranged from 17.5 to 30 mg/kg of IBW, depending on renal function. Overall, simulation showed that 55.8% (95% CI; 47-64%) of patients would achieve the target AUC with suggested dosages. Discussion: A PK model has been validated for vancomycin administered by CI in ICU patients, including patients under CRRT. Our model-informed precision dosing approach may help for early optimization of vancomycin exposure in such patients.

Keywords: ICU; continuous infusion; pharmacokinetics; vancomycin.

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Conflict of interest statement

The authors have no conflict of interest that are relevant to the content of this study.

Figures

Figure 1
Figure 1
Observed versus predicted vancomycin concentrations in the learning dataset.
Figure 2
Figure 2
Internal validation of the model: prediction-corrected visual predictive checks.
Figure 3
Figure 3
Observed vs. predicted concentration in the validation dataset.
See this image and copyright information in PMC

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