Model-Informed Precision Dosing of Antibiotics in Osteoarticular Infections

Abstract

As a heterogeneous and wide inflammation, osteoarticular infection (OAI) shows an increasing incidence in recent years. Staphylococcus aureus is the most important pathogen causing OAI. The antibiotic treatment will affect the outcomes of OAI patients, and the drug selection and dosage regimen highly rely on patients' variability, pathogen susceptibility, and drug property like bone permeability. Model-informed precision dosing (MIPD) provides options to describe and quantify the pharmacokinetic (PK) variability of the OAI population using different models, such as the population pharmacokinetic (PPK) model and physiological-based pharmacokinetic (PB/PK) model. In the present review, we highlighted that the MIPD of antibiotics played a critical role in OAI and listed the dose regimen recommended by the model. Collectively, our current study provided a valuable reference for the treatment of patients and improved the safety and efficiency of drug use.

Penetration of Vancomycin into Noninfected Bone in Patients Undergoing Total Joint Arthroplasty Evaluated by a Minimal Physiologically Based Population Pharmacokinetic Modeling Approach

“…It offers a promising approach as a step toward an improved understanding of the vancomycin PK in bone, and ultimately model-informed precision dosing of antibiotics used to treat established bone infections. 24 Setting important population PK parameters to their physiological values enabled the simultaneous description of the vancomycin serum concentrations over time and the extent of penetration into bone across a 4fold dose range and single and multiple doses with only four estimated population PK parameters. The estimated population mean clearance of 2.12 L/h/70 kg 0.75 was within the range of values (0.334 to 8.75 L/h) reported in a recent review of vancomycin population PK analyses in adults.…”

“…The mPBPK model developed in the current study incorporates physiological information on blood volume, cardiac output, bone volume, and the blood flow to bone. It offers a promising approach as a step toward an improved understanding of the vancomycin PK in bone, and ultimately model-informed precision dosing of antibiotics used to treat established bone infections . Setting important population PK parameters to their physiological values enabled the simultaneous description of the vancomycin serum concentrations over time and the extent of penetration into bone across a 4-fold dose range and single and multiple doses with only four estimated population PK parameters.…”