Drug Monitoring of Antibiotics in the Era of Precision Dosing

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Clinical Pharmaceutics".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 618

Special Issue Editors


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Guest Editor
1. Pharmacology and Toxicology Unit, Department of Internal Medicine, University of Genoa, Viale Benedetto XV 2, 16132 Genoa, Italy
2. Clinical Pharmacology Unit, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128 Genoa, Italy
Interests: drug monitoring; antibiotics; precision dosing; pharmacokinetics; pharmacodynamics; PK/PD relationship; clinical pharmacology; clinical pharmacokinetics; population pharmacokinetics

E-Mail Website
Guest Editor
1. Pharmacology and Toxicology Unit, Department of Internal Medicine, University of Genoa, Viale Benedetto XV 2, 16132 Genoa, Italy
2. Clinical Pharmacology Unit, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128 Genoa, Italy
Interests: drug monitoring; antibiotics; precision dosing; pharmacokinetics; pharmacodynamics; PK/PD relationship; clinical pharmacology; population pharmacokinetics; model-informed precision dosing

Special Issue Information

Dear Colleagues,

Drug monitoring of antibiotics is a fundamental tool for the attainment of the PK/PD targets associated with favourable clinical outcomes and a reduction in the toxicity of established and novel drugs. Nowadays, precision dosing of antibiotics is spreading in clinical practice, thanks to the diffusion of gold-standard techniques of drug quantitation like LC-MS/MS. The specific quantification of antibiotics enables the reliable set up of population pharmacokinetic models to guide clinician dosing adjustments in specific patient populations. Expert clinical pharmacologists’ measurement and interpretation of drug concentrations is essential to support the antimicrobial stewardship, along with the informed opinion of fellow infectivologists and microbiologists, to unlock the full clinical benefit of a therapeutic intervention.

In this Special Issue of Pharmaceutics, we aim to publish novel clinical evidence and/or reviews supporting dosing optimization of antibiotic treatments by therapeutic drug monitoring and PK/PD pharmacokinetics principles for precision dosing recommendations.

Dr. Francesca Mattioli
Dr. Giammarco Baiardi
Guest Editors

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Keywords

  • drug monitoring
  • antibiotics
  • precision dosing
  • TDM-guided dosing
  • PK/PD relationship
  • HPLC
  • LC-MS/MS
  • antimicrobial stewardship
  • clinical pharmacology
  • population pharmacokinetics
  • model-informed precision dosing

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Published Papers (1 paper)

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Research

14 pages, 1675 KiB  
Article
Pharmacokinetics of Piperacillin–Tazobactam in Critically Ill Patients with Open Abdomen and Vacuum-Assisted Wound Closure: Dosing Considerations Using Monte Carlo Simulation
by Cédric Carrié, Jesse Butruille, Sophie Maingault, Alexandre Lannou, Vincent Dubuisson, Laurent Petit, Matthieu Biais and Dominique Breilh
Pharmaceutics 2024, 16(9), 1191; https://doi.org/10.3390/pharmaceutics16091191 - 9 Sep 2024
Viewed by 318
Abstract
Background: Open abdomen with vacuum-assisted wound closure therapy (OA/VAC) is frequently used in critically ill patients although the impact of OA/VAC on antibiotics pharmacokinetics (PK) remains unknown. We thus aimed to characterize the PK of piperacillin–tazobactam (PTZ) in critically ill patients with OA/VAC [...] Read more.
Background: Open abdomen with vacuum-assisted wound closure therapy (OA/VAC) is frequently used in critically ill patients although the impact of OA/VAC on antibiotics pharmacokinetics (PK) remains unknown. We thus aimed to characterize the PK of piperacillin–tazobactam (PTZ) in critically ill patients with OA/VAC and assess the optimal dosing regimens based on pharmacodynamics (PD) target attainment. Methods: Over a 15-month study period, 45 patients with OA/VAC treated with PTZ administered continuously and adapted to 24 h creatinine clearance (CLCR) underwent measurements of free concentrations in their plasma, urine, VAC exudate, and peritoneal fluid. Population PK modeling was performed considering the effect of covariates, and Monte Carlo simulations were employed to determine the probability of target attainment (PTA) for the PK/PD targets (100% fT > 16 mg/L) in the plasma and at the peritoneal site at steady state. Results: Piperacillin concentrations were described using a two-compartment model, with age and total body weight as significant covariates for central volume of distribution (V1) and estimated renal function for clearance (CL). Tazobactam concentrations were described using a two-compartment model with estimated renal function as a significant covariate. The central volume of distributions V1 of piperacillin and tazobactam were 21.2 and 23.2 L, respectively. The VAC-induced peritoneal clearance was negligible compared to renal clearance. Most patients achieved the desirable PK/PD target when using a CLCR-pondered PTZ dosing regimen from 12 g/1.5 g/day to 20 g/2.5 g/day. Conclusions: Despite a wide inter-individual variability, the influence of OA/VAC on piperacillin and tazobactam PK parameters is not straightforward. The use of a CLCR-pondered PTZ dosing regimen from 12 g/1.5 g/day to 20 g/2.5 g/day is needed to reach a PTA > 85%. Full article
(This article belongs to the Special Issue Drug Monitoring of Antibiotics in the Era of Precision Dosing)
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