Contribution of immunocompetence to the antibacterial activities of ciprofloxacin and moxifloxacin in an in vitro pharmacodynamic model

Infection
A Dalhoff

Abstract

Traditional in vitro models used to simulate human pharmacokinetics and to characterize the pharmacodynamics of antibacterial agents represent a totally immunosuppressed condition. However, host defense mechanisms contribute to the elimination of the pathogen from the infectious site in most of the patients suffering from infectious diseases. Therefore, the attempt was made to introduce immunocompetence into an in vitro pharmacodynamic model. Immunocompetence was added either by using J774 macrophages growing as adherent monolayers in cell culture flasks, or by using a newly developed ex vivo model. This ex vivo model consists of sponges which have been implanted into rats for 24 h. After 24 h the sponges are explanted; at this point in time the sponges are soaked with an inflammatory exudate to which the bacteria to be tested are added. Into a slightly modified one-compartment model according to Grasso the explanted sponges which are entrapped in dialysis tubings are added. Neither the bacteria nor the inflammatory proteins nor the immunocompetent cells escape from the explants. Thus, it is possible to simulate antibiotic kinetics without diluting bacteria, the polymorphonuclear cells (PMN) or the inflammatory exudates. This e...Continue Reading

Citations

Dec 6, 2008·Journal of Theoretical Biology·Andreas HandelBruce R Levin
Jan 18, 2006·Biochemical Pharmacology·Axel DalhoffRoger Echols
Nov 22, 2017·Antimicrobial Agents and Chemotherapy·Axel Dalhoff
Sep 6, 2014·Medical Microbiology and Immunology·Olachi AnuforomLaura V Piddock
Sep 12, 2020·Advanced Materials·Saber Amin YavariMichiel Croes

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