Cargando…
Population Pharmacokinetics and Monte Carlo Simulation of Cefepime in Critically Ill Patients with Hospital-Acquired/Ventilator-Associated Pneumonia
BACKGROUND: This study aimed to investigate the population pharmacokinetics (PK) profile and determine the optimal dosage regimen of cefepime in critically ill adult patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP). MATERIALS AND METHODS: Population-PK models...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Society of Infectious Diseases; Korean Society for Antimicrobial Therapy; The Korean Society for AIDS
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10079447/ https://www.ncbi.nlm.nih.gov/pubmed/36450287 http://dx.doi.org/10.3947/ic.2022.0087 |
_version_ | 1785020723699384320 |
---|---|
author | Seo, Hyeonji Kim, Yong Kyun Park, Sunghoon Kim, Hwan-il Lee, Dong-Hwan |
author_facet | Seo, Hyeonji Kim, Yong Kyun Park, Sunghoon Kim, Hwan-il Lee, Dong-Hwan |
author_sort | Seo, Hyeonji |
collection | PubMed |
description | BACKGROUND: This study aimed to investigate the population pharmacokinetics (PK) profile and determine the optimal dosage regimen of cefepime in critically ill adult patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP). MATERIALS AND METHODS: Population-PK models for cefepime were developed using a nonlinear mixed-effect modeling approach. The percentage of time within 24 h in which the free concentration exceeded the minimum inhibitory concentration (MIC) at a steady state (50%fT(>MIC), 100%fT(>MIC), and 100%fT(>4×MIC)) for various combinations of dosage regimens and renal function was explored using Monte Carlo simulation. RESULTS: Twenty-one patients were prospectively enrolled in this study. Cefepime PK was best described using a two-compartment model in which creatinine clearance (CL(CR)) through Cockcroft-Gault (CG) was a significant covariate for the total clearance of cefepime. The simulation results to determine the optimal cefepime dosing regimen for 50%fT(>MIC) as treatment target with C(min) <20 mg/L as safety target showed that a dosage regimen of 2 g through intravenous (IV) infusion every 12 h administered over 4 h was optimal at an MIC of 4 mg/L, rather than the currently recommended dosage regimen of 2 g administered through IV infusion every 8 h, in patients with normal renal function (CL(CR) = 90 - 130 mL/min). For a treatment target of 100%fT(>MIC) with C(min) <35 mg/L as a safety target, a dosage regimen of 0.75 g administered through continuous infusion over 24 h would be sufficient at an MIC equal to or less than 8 mg/L in patients with renal dysfunction (CL(CR) = 10 - 30 mL/min). CONCLUSION: Our results suggest that clinicians should consider renal function and potential neurotoxicity when deciding the dosing regimen of cefepime in critically ill patients with HAP or VAP. Therapeutic drug monitoring (TDM) to adjust cefepime trough levels may be useful to improve clinical outcomes and reduce cefepime neurotoxicity. |
format | Online Article Text |
id | pubmed-10079447 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Korean Society of Infectious Diseases; Korean Society for Antimicrobial Therapy; The Korean Society for AIDS |
record_format | MEDLINE/PubMed |
spelling | pubmed-100794472023-04-08 Population Pharmacokinetics and Monte Carlo Simulation of Cefepime in Critically Ill Patients with Hospital-Acquired/Ventilator-Associated Pneumonia Seo, Hyeonji Kim, Yong Kyun Park, Sunghoon Kim, Hwan-il Lee, Dong-Hwan Infect Chemother Original Article BACKGROUND: This study aimed to investigate the population pharmacokinetics (PK) profile and determine the optimal dosage regimen of cefepime in critically ill adult patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP). MATERIALS AND METHODS: Population-PK models for cefepime were developed using a nonlinear mixed-effect modeling approach. The percentage of time within 24 h in which the free concentration exceeded the minimum inhibitory concentration (MIC) at a steady state (50%fT(>MIC), 100%fT(>MIC), and 100%fT(>4×MIC)) for various combinations of dosage regimens and renal function was explored using Monte Carlo simulation. RESULTS: Twenty-one patients were prospectively enrolled in this study. Cefepime PK was best described using a two-compartment model in which creatinine clearance (CL(CR)) through Cockcroft-Gault (CG) was a significant covariate for the total clearance of cefepime. The simulation results to determine the optimal cefepime dosing regimen for 50%fT(>MIC) as treatment target with C(min) <20 mg/L as safety target showed that a dosage regimen of 2 g through intravenous (IV) infusion every 12 h administered over 4 h was optimal at an MIC of 4 mg/L, rather than the currently recommended dosage regimen of 2 g administered through IV infusion every 8 h, in patients with normal renal function (CL(CR) = 90 - 130 mL/min). For a treatment target of 100%fT(>MIC) with C(min) <35 mg/L as a safety target, a dosage regimen of 0.75 g administered through continuous infusion over 24 h would be sufficient at an MIC equal to or less than 8 mg/L in patients with renal dysfunction (CL(CR) = 10 - 30 mL/min). CONCLUSION: Our results suggest that clinicians should consider renal function and potential neurotoxicity when deciding the dosing regimen of cefepime in critically ill patients with HAP or VAP. Therapeutic drug monitoring (TDM) to adjust cefepime trough levels may be useful to improve clinical outcomes and reduce cefepime neurotoxicity. The Korean Society of Infectious Diseases; Korean Society for Antimicrobial Therapy; The Korean Society for AIDS 2023-03 2022-11-11 /pmc/articles/PMC10079447/ /pubmed/36450287 http://dx.doi.org/10.3947/ic.2022.0087 Text en Copyright © 2023 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Seo, Hyeonji Kim, Yong Kyun Park, Sunghoon Kim, Hwan-il Lee, Dong-Hwan Population Pharmacokinetics and Monte Carlo Simulation of Cefepime in Critically Ill Patients with Hospital-Acquired/Ventilator-Associated Pneumonia |
title | Population Pharmacokinetics and Monte Carlo Simulation of Cefepime in Critically Ill Patients with Hospital-Acquired/Ventilator-Associated Pneumonia |
title_full | Population Pharmacokinetics and Monte Carlo Simulation of Cefepime in Critically Ill Patients with Hospital-Acquired/Ventilator-Associated Pneumonia |
title_fullStr | Population Pharmacokinetics and Monte Carlo Simulation of Cefepime in Critically Ill Patients with Hospital-Acquired/Ventilator-Associated Pneumonia |
title_full_unstemmed | Population Pharmacokinetics and Monte Carlo Simulation of Cefepime in Critically Ill Patients with Hospital-Acquired/Ventilator-Associated Pneumonia |
title_short | Population Pharmacokinetics and Monte Carlo Simulation of Cefepime in Critically Ill Patients with Hospital-Acquired/Ventilator-Associated Pneumonia |
title_sort | population pharmacokinetics and monte carlo simulation of cefepime in critically ill patients with hospital-acquired/ventilator-associated pneumonia |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10079447/ https://www.ncbi.nlm.nih.gov/pubmed/36450287 http://dx.doi.org/10.3947/ic.2022.0087 |
work_keys_str_mv | AT seohyeonji populationpharmacokineticsandmontecarlosimulationofcefepimeincriticallyillpatientswithhospitalacquiredventilatorassociatedpneumonia AT kimyongkyun populationpharmacokineticsandmontecarlosimulationofcefepimeincriticallyillpatientswithhospitalacquiredventilatorassociatedpneumonia AT parksunghoon populationpharmacokineticsandmontecarlosimulationofcefepimeincriticallyillpatientswithhospitalacquiredventilatorassociatedpneumonia AT kimhwanil populationpharmacokineticsandmontecarlosimulationofcefepimeincriticallyillpatientswithhospitalacquiredventilatorassociatedpneumonia AT leedonghwan populationpharmacokineticsandmontecarlosimulationofcefepimeincriticallyillpatientswithhospitalacquiredventilatorassociatedpneumonia |