Population Pharmacokinetics and Dosing Simulation of Vancomycin Administered by Continuous Injection in Critically Ill Patient
<b>Background:</b> 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 po...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/10/10/1228 |
| _version_ | 1797515502555234304 |
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| author | Romain Garreau Benoît Falquet Lisa Mioux Laurent Bourguignon Tristan Ferry Michel Tod Florent Wallet Arnaud Friggeri Jean-Christophe Richard Sylvain Goutelle |
| author_facet | Romain Garreau Benoît Falquet Lisa Mioux Laurent Bourguignon Tristan Ferry Michel Tod Florent Wallet Arnaud Friggeri Jean-Christophe Richard Sylvain Goutelle |
| author_sort | Romain Garreau |
| collection | DOAJ |
| description | <b>Background:</b> 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. <b>Methods:</b> 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 (CR<sub>CL</sub>) 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). <b>Results:</b> 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 CR<sub>CL</sub>. 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. <b>Discussion:</b> 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. |
| first_indexed | 2024-03-10T06:46:20Z |
| format | Article |
| id | doaj.art-78fb0ccf233944a0b7e1cd991e04717c |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T06:46:20Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-78fb0ccf233944a0b7e1cd991e04717c2023-11-22T17:14:07ZengMDPI AGAntibiotics2079-63822021-10-011010122810.3390/antibiotics10101228Population Pharmacokinetics and Dosing Simulation of Vancomycin Administered by Continuous Injection in Critically Ill PatientRomain Garreau0Benoît Falquet1Lisa Mioux2Laurent Bourguignon3Tristan Ferry4Michel Tod5Florent Wallet6Arnaud Friggeri7Jean-Christophe Richard8Sylvain Goutelle9Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, 69005 Lyon, FranceHospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, 69005 Lyon, FranceHospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, 69005 Lyon, FranceHospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, 69005 Lyon, FranceFacultés de Médecine et de Pharmacie de Lyon, Université Lyon 1, 69008 Lyon, FranceHospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, 69005 Lyon, FranceCentre Hospitalier Lyon Sud, Hospices Civils de Lyon, Critical Care, 69495 Pierre-Bénite, FranceFacultés de Médecine et de Pharmacie de Lyon, Université Lyon 1, 69008 Lyon, FranceFacultés de Médecine et de Pharmacie de Lyon, Université Lyon 1, 69008 Lyon, FranceHospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, 69005 Lyon, France<b>Background:</b> 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. <b>Methods:</b> 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 (CR<sub>CL</sub>) 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). <b>Results:</b> 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 CR<sub>CL</sub>. 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. <b>Discussion:</b> 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.https://www.mdpi.com/2079-6382/10/10/1228vancomycinpharmacokineticscontinuous infusionICU |
| spellingShingle | Romain Garreau Benoît Falquet Lisa Mioux Laurent Bourguignon Tristan Ferry Michel Tod Florent Wallet Arnaud Friggeri Jean-Christophe Richard Sylvain Goutelle Population Pharmacokinetics and Dosing Simulation of Vancomycin Administered by Continuous Injection in Critically Ill Patient Antibiotics vancomycin pharmacokinetics continuous infusion ICU |
| title | Population Pharmacokinetics and Dosing Simulation of Vancomycin Administered by Continuous Injection in Critically Ill Patient |
| title_full | Population Pharmacokinetics and Dosing Simulation of Vancomycin Administered by Continuous Injection in Critically Ill Patient |
| title_fullStr | Population Pharmacokinetics and Dosing Simulation of Vancomycin Administered by Continuous Injection in Critically Ill Patient |
| title_full_unstemmed | Population Pharmacokinetics and Dosing Simulation of Vancomycin Administered by Continuous Injection in Critically Ill Patient |
| title_short | Population Pharmacokinetics and Dosing Simulation of Vancomycin Administered by Continuous Injection in Critically Ill Patient |
| title_sort | population pharmacokinetics and dosing simulation of vancomycin administered by continuous injection in critically ill patient |
| topic | vancomycin pharmacokinetics continuous infusion ICU |
| url | https://www.mdpi.com/2079-6382/10/10/1228 |
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