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Real-Time TDM-Based Expert Clinical Pharmacological Advice Program for Attaining Aggressive Pharmacokinetic/Pharmacodynamic Target of Continuous Infusion Meropenem in the Treatment of Critically Ill Patients with Documented Gram-Negative Infections Undergoing Continuous Veno-Venous Hemodiafiltration
(1) Objectives: to describe the pharmacokinetic/pharmacodynamic (PK/PD) profile of continuous infusion (CI) meropenem in critical patients with documented Gram-negative infections undergoing continuous veno-venous hemodiafiltration (CVVHDF) and to assess the relationship with microbiological outcome...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10604776/ https://www.ncbi.nlm.nih.gov/pubmed/37887225 http://dx.doi.org/10.3390/antibiotics12101524 |
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author | Gatti, Milo Rinaldi, Matteo Tonetti, Tommaso Siniscalchi, Antonio Viale, Pierluigi Pea, Federico |
author_facet | Gatti, Milo Rinaldi, Matteo Tonetti, Tommaso Siniscalchi, Antonio Viale, Pierluigi Pea, Federico |
author_sort | Gatti, Milo |
collection | PubMed |
description | (1) Objectives: to describe the pharmacokinetic/pharmacodynamic (PK/PD) profile of continuous infusion (CI) meropenem in critical patients with documented Gram-negative infections undergoing continuous veno-venous hemodiafiltration (CVVHDF) and to assess the relationship with microbiological outcome. (2) Methods: Data were retrospectively retrieved for patients admitted to the general and the post-transplant intensive care units in the period October 2022–May 2023 who underwent CVVHDF during treatment with CI meropenem optimized by means of a real-time therapeutic drug monitoring (TDM)-based expert clinical pharmacological advice (ECPA) program for documented Gram-negative infections. Steady-state meropenem plasma concentrations were measured, and the free fractions (fC(ss)) were calculated. Meropenem total clearance (CL(tot)) was calculated at each TDM assessment, and the impact of CVVHDF dose intensity and of residual diuresis on CL(tot) was investigated by means of linear regression. Optimal meropenem PK/PD target attainment was defined as an fC(ss)/MIC ratio > 4. The relationship between meropenem PK/PD target attainment and microbiological outcome was assessed. (3) Results: A total of 24 critical patients (median age 68 years; male 62.5%) with documented Gram-negative infections were included. Median (IQR) meropenem fC(ss) was 19.9 mg/L (17.4–28.0 mg/L). Median (IQR) CL(tot) was 3.89 L/h (3.28–5.29 L/h), and median (IQR) CVVHDF dose intensity was 37.4 mL/kg/h (33.8–44.6 mL/kg/h). Meropenem dosing adjustments were provided in 20 out of 24 first TDM assessments (83.3%, all decreases) and overall in 26 out of the 51 total ECPA cases (51.0%). Meropenem PK/PD target attainment was always optimal, and microbiological eradication was achieved in 90.5% of assessable cases. (4) Conclusion: the real-time TDM-guided ECPA program was useful in attaining aggressive PK/PD targeting with CI meropenem in critically ill patients undergoing high-intensity CVVHDF and allowed microbiological eradication in most cases with dosing regimens ranging between 125 and 500 mg q6h over 6 h. |
format | Online Article Text |
id | pubmed-10604776 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106047762023-10-28 Real-Time TDM-Based Expert Clinical Pharmacological Advice Program for Attaining Aggressive Pharmacokinetic/Pharmacodynamic Target of Continuous Infusion Meropenem in the Treatment of Critically Ill Patients with Documented Gram-Negative Infections Undergoing Continuous Veno-Venous Hemodiafiltration Gatti, Milo Rinaldi, Matteo Tonetti, Tommaso Siniscalchi, Antonio Viale, Pierluigi Pea, Federico Antibiotics (Basel) Article (1) Objectives: to describe the pharmacokinetic/pharmacodynamic (PK/PD) profile of continuous infusion (CI) meropenem in critical patients with documented Gram-negative infections undergoing continuous veno-venous hemodiafiltration (CVVHDF) and to assess the relationship with microbiological outcome. (2) Methods: Data were retrospectively retrieved for patients admitted to the general and the post-transplant intensive care units in the period October 2022–May 2023 who underwent CVVHDF during treatment with CI meropenem optimized by means of a real-time therapeutic drug monitoring (TDM)-based expert clinical pharmacological advice (ECPA) program for documented Gram-negative infections. Steady-state meropenem plasma concentrations were measured, and the free fractions (fC(ss)) were calculated. Meropenem total clearance (CL(tot)) was calculated at each TDM assessment, and the impact of CVVHDF dose intensity and of residual diuresis on CL(tot) was investigated by means of linear regression. Optimal meropenem PK/PD target attainment was defined as an fC(ss)/MIC ratio > 4. The relationship between meropenem PK/PD target attainment and microbiological outcome was assessed. (3) Results: A total of 24 critical patients (median age 68 years; male 62.5%) with documented Gram-negative infections were included. Median (IQR) meropenem fC(ss) was 19.9 mg/L (17.4–28.0 mg/L). Median (IQR) CL(tot) was 3.89 L/h (3.28–5.29 L/h), and median (IQR) CVVHDF dose intensity was 37.4 mL/kg/h (33.8–44.6 mL/kg/h). Meropenem dosing adjustments were provided in 20 out of 24 first TDM assessments (83.3%, all decreases) and overall in 26 out of the 51 total ECPA cases (51.0%). Meropenem PK/PD target attainment was always optimal, and microbiological eradication was achieved in 90.5% of assessable cases. (4) Conclusion: the real-time TDM-guided ECPA program was useful in attaining aggressive PK/PD targeting with CI meropenem in critically ill patients undergoing high-intensity CVVHDF and allowed microbiological eradication in most cases with dosing regimens ranging between 125 and 500 mg q6h over 6 h. MDPI 2023-10-10 /pmc/articles/PMC10604776/ /pubmed/37887225 http://dx.doi.org/10.3390/antibiotics12101524 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gatti, Milo Rinaldi, Matteo Tonetti, Tommaso Siniscalchi, Antonio Viale, Pierluigi Pea, Federico Real-Time TDM-Based Expert Clinical Pharmacological Advice Program for Attaining Aggressive Pharmacokinetic/Pharmacodynamic Target of Continuous Infusion Meropenem in the Treatment of Critically Ill Patients with Documented Gram-Negative Infections Undergoing Continuous Veno-Venous Hemodiafiltration |
title | Real-Time TDM-Based Expert Clinical Pharmacological Advice Program for Attaining Aggressive Pharmacokinetic/Pharmacodynamic Target of Continuous Infusion Meropenem in the Treatment of Critically Ill Patients with Documented Gram-Negative Infections Undergoing Continuous Veno-Venous Hemodiafiltration |
title_full | Real-Time TDM-Based Expert Clinical Pharmacological Advice Program for Attaining Aggressive Pharmacokinetic/Pharmacodynamic Target of Continuous Infusion Meropenem in the Treatment of Critically Ill Patients with Documented Gram-Negative Infections Undergoing Continuous Veno-Venous Hemodiafiltration |
title_fullStr | Real-Time TDM-Based Expert Clinical Pharmacological Advice Program for Attaining Aggressive Pharmacokinetic/Pharmacodynamic Target of Continuous Infusion Meropenem in the Treatment of Critically Ill Patients with Documented Gram-Negative Infections Undergoing Continuous Veno-Venous Hemodiafiltration |
title_full_unstemmed | Real-Time TDM-Based Expert Clinical Pharmacological Advice Program for Attaining Aggressive Pharmacokinetic/Pharmacodynamic Target of Continuous Infusion Meropenem in the Treatment of Critically Ill Patients with Documented Gram-Negative Infections Undergoing Continuous Veno-Venous Hemodiafiltration |
title_short | Real-Time TDM-Based Expert Clinical Pharmacological Advice Program for Attaining Aggressive Pharmacokinetic/Pharmacodynamic Target of Continuous Infusion Meropenem in the Treatment of Critically Ill Patients with Documented Gram-Negative Infections Undergoing Continuous Veno-Venous Hemodiafiltration |
title_sort | real-time tdm-based expert clinical pharmacological advice program for attaining aggressive pharmacokinetic/pharmacodynamic target of continuous infusion meropenem in the treatment of critically ill patients with documented gram-negative infections undergoing continuous veno-venous hemodiafiltration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10604776/ https://www.ncbi.nlm.nih.gov/pubmed/37887225 http://dx.doi.org/10.3390/antibiotics12101524 |
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