In Vitro and Animal PK/PD Models

Abstract

A large variety of in vitro and animal models have been used to characterize the pharmacodynamics of antimicrobials. In vitro kill curves report two different patterns of antimicrobial killing (concentration dependent and time dependent) that can be followed by persistent effects that delay bacterial regrowth. In vitro kinetic models using dilution or dialysis have the ability to simulate the changing drug concentrations observed in humans and study their effect on different bacteria. New hollow-fiber dialysis models have reduced the chance of contamination and have allowed longer studies of the emergence and suppression of resistant mutants. Animal models have the advantage of determining antimicrobial efficacy at specific body sites such as the thigh in mice, the peritoneum in mice and rats, the lung in mice, rats, and guinea pigs, endocarditis in rabbits and rats, and meningitis in rabbits. However, clearance of antimicrobials is more rapid in animals than in humans. Many factors, such as inoculum, media, growth-phase of the organism, site of infection, drug concentrations to measure correct drug exposure, presence of neutropenia, and measurement of outcome by colony-forming units (CFUs), survival/mortality, or another form of assessment, need to be considered to develop meaningful conclusions.

En Route towards European Clinical Breakpoints for Veterinary Antimicrobial Susceptibility Testing: A Position Paper Explaining the VetCAST Approach

“…When there are no specific veterinary data, a default value of the predictive index is selected from human medicine. The rationale for using values from human medicine is that they are frequently derived from studies conducted in animal disease models ( Craig, 2014a ).…”

In vivo Pharmacokinetic/Pharmacodynamic (PK/PD) Profiles of Tulathromycin in an Experimental Intraperitoneal Haemophilus parasuis Infection Model in Neutropenic Guinea Pigs

“…We speculate that the metabolism and distribution of tulathromycin in lungs may have been reduced by the swollen lesions that we observed in the tissues. Moreover, laboratory animal models, commonly used in studies, typically have much faster rates of elimination of antibiotics than target animals (75). Antibiotic resistance and its development are a complex subject.…”

Probiotics and Postbiotics from Food to Health: Antimicrobial Experimental Confirmation

“…The in vitro studies offer required information about antimicrobial agents on susceptibility responses [73], exposure times, and optimal concentrations [74]. However, these studies have their limitations, for instance, the bulk of antimicrobial agents that are active in vitro lack significant antimicrobial activity in vivo, and vice versa sometimes occurs [73].…”

“…However, these studies have their limitations, for instance, the bulk of antimicrobial agents that are active in vitro lack significant antimicrobial activity in vivo, and vice versa sometimes occurs [73]. The strength of animal models in determining antimicrobial efficacy is that the study can be ascertained at specific body sites, for example, skin, thigh, lung, peritoneum, meninges, and endocardia [74]. Furthermore, antimicrobial agents are altered by host factors such as metabolism and the immune system in an animal model [74].…”

“…The strength of animal models in determining antimicrobial efficacy is that the study can be ascertained at specific body sites, for example, skin, thigh, lung, peritoneum, meninges, and endocardia [74]. Furthermore, antimicrobial agents are altered by host factors such as metabolism and the immune system in an animal model [74]. Consequently, animal models bridge the gap between in vitro and clinical trials [73] and are indispensable for authentication of probiotic antimicrobial activity.…”