Pharmacokinetic/pharmacodynamic (PK/PD) integration models are used to investigate the antimicrobial activity characteristics of drugs targeting pathogenic bacteria through comprehensive analysis of the interactions between PK and PD parameters. PK/PD models have been widely applied in the development of new drugs, optimization of the dosage regimen, and prevention and treatment of drug-resistant bacteria. In PK/PD analysis, minimal inhibitory concentration (MIC) is the most commonly applied PD parameter. However, accurately determining MIC is challenging and this can influence the therapeutic effect. Therefore, it is necessary to optimize PD indices to generate more rational results. Researchers have attempted to optimize PD parameters using mutant prevention concentration (MPC)-based PK/PD models, multiple PD parameter-based PK/PD models, kill rate-based PK/PD models, and others. In this review, we discuss progress on PD parameters for PK/PD models to provide a valuable reference for drug development, determining the dosage regimen, and preventing drug-resistant mutations.
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http://dx.doi.org/10.3389/fvets.2022.860472 | DOI Listing |
J Antimicrob Chemother
December 2024
Department of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Hamburg, Germany.
Background: MDR Gram-negative bacteria, such as ESBL-producing and carbapenemase-producing Klebsiella pneumoniae, represent major global health threats. Treatment options are limited due to increasing resistance and slowed development of novel antimicrobials, making it necessary to apply effective combination therapies based on approved antibiotics.
Objectives: To quantitatively evaluate the synergistic potential of meropenem and fosfomycin against carbapenem-resistant K.
Clin Pharmacokinet
December 2024
Department of Anesthesiology, University of Groningen, University Medical Center Groningen, P. O. Box 30001, 9700 RB, Groningen, The Netherlands.
Background And Objectives: The pharmacokinetics (PK) of piperacillin/tazobactam (PIP/TAZ) is highly variable across different patient populations and there are controversies regarding non-linear elimination as well as the fraction unbound of PIP (f). This has led to a plethora of subgroup-specific models, increasing the risk of misusing published models when optimising dosing regimens. In this study, we aimed to develop a single model to simultaneously describe the PK of PIP/TAZ in diverse patient populations and evaluate the current dosing recommendations by predicting the PK/pharmacodynamics (PD) target attainment throughout life.
View Article and Find Full Text PDFJAC Antimicrob Resist
December 2024
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA.
Background: Sulbactam is an effective therapy for infections. Previous sulbactam pharmacokinetics/pharmacodynamics (PK/PD) analyses established exposure efficacy targets in plasma against pneumonia. Herein, we established sulbactam efficacy targets in epithelial lining fluid (ELF).
View Article and Find Full Text PDFJ Antimicrob Chemother
December 2024
Facultés de Médecine et de Pharmacie de Lyon, Univ Lyon, Université Claude Bernard Lyon 1, Lyon, France.
Background And Objectives: Cefiderocol approved dosages are based on a prolonged infusion (PI) of 3 h that may not be adequate in all settings The objective of this study was to identify alternative cefiderocol dosage regimens based on short infusion (SI) or continuous infusion (CI).
Methods: We performed 1000-patient pharmacokinetic/pharmacodynamic (PK/PD) simulations based on a reference population model. Drug penetration into the epithelial lining fluid (ELF) was considered for pneumonia.
Clin Pharmacokinet
December 2024
Pharmacy Service, Division of Medicines, Hospital Clinic of Barcelona, Universitat de Barcelona, Barcelona, Spain.
In recent years, many population pharmacokinetic (popPK) models have been developed for echinocandins to better understand the pharmacokinetics (PK) of these antifungals. This comprehensive review aimed to summarize popPK models of echinocandins (micafungin, caspofungin, anidulafungin, and rezafungin), by focusing on dosage optimization to maximize the probability of attaining the PK/PD target proposed in special populations. A search in PubMed, Embase, Web of Science, and Scopus, supplemented by the bibliography of relevant articles, was conducted from inception to March 2024, including both observational and prospective trials.
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