Abstract
Antimicrobial resistance is a major public health issue. The pharmacokinetic/pharmacodynamic (PK/PD) model is an essential tool to optimize dosage regimens and alleviate the emergence of resistance. The semi-mechanistic PK/PD model is a mathematical quantitative tool to capture the relationship between dose, exposure, and response, in terms of the mechanism. Understanding the different resistant mechanisms of bacteria to various antibacterials and presenting this as mathematical equations, the semi-mechanistic PK/PD model can capture and simulate the progress of bacterial growth and the variation in susceptibility. In this review, we outline the bacterial growth model and antibacterial effect model, including different resistant mechanisms, such as persisting resistance, adaptive resistance, and pre-existing resistance, of antibacterials against bacteria. The application of the semi-mechanistic PK/PD model, such as the determination of PK/PD breakpoints, combination therapy, and dosage optimization, are also summarized. Additionally, it is important to integrate the PD effect, such as the inoculum effect and host response, in order to develop a comprehensive mechanism model. In conclusion, with the semi-mechanistic PK/PD model, the dosage regimen can be reasonably determined, which can suppress bacterial growth and resistance development.
Highlights
Publisher’s Note: MDPI stays neutralThe emerging antimicrobial resistance (AMR) of bacteria threatens clinical therapeutics
The semi-mechanistic PD model can parameterize the processes of bacterial growth and antibacterial effect and can be integrated with the PK model to simulate the growth, death, and resistance emergence of the bacterial population under different antibacterial exposures
Compared with the mechanistic PK/PD model, the semi-mechanistic PK/PD model focuses on the macroscopic description of the microbial system
Summary
The emerging antimicrobial resistance (AMR) of bacteria threatens clinical therapeutics. Pharmaceutics 2022, 14, x contributes to the adjustment and optimization of dosage regimens, aiming to provide enough antibacterial effect for an infection caused by drug-resistant bacteria [4]. The. PK/PD model of antimicrobials has been categorized by three PK/PD indices, which are comprised of a summary endpoint of drug exposure correlated with the minimum inhibitory concentration (MIC). The MIC is determined at only one time point (over a 16–18 h period), with a low initial inoculum (i.e., usually in the absence of resistant populations), and utilizing a constant inoculum antimicrobial concentration, which is opposed to the dynamic changes in the in vivo condition [5].
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