A review of animal models used for antibiotic evaluation

Abstract

One of the foremost challenges of drug discovery in any therapeutic area is solidifying the correlation between in vitro activity and clinical efficacy. Intermediate between those two points is the validation that affecting a particular target in vivo will lead to a therapeutic benefit. In antibacterial drug discovery, there is an implicit advantage from the start, in that the targets are bacteria, and it is relatively straightforward to ascertain in vitro whether a compound has the desired effect (i.e., bacterial cell killing) and to understand the mechanism by which that occurs. The downstream criteria, whether a compound reaches the site of infection and attains levels necessary to affect bacterial viability, can be evaluated in animal models of infection. That is, once it is clear that a test compound is able to kill bacteria, and it is established that it can achieve appropriate concentrations in infection sites, it is possible to extrapolate that the desired clinical effect can be expected. In this way, animal models of infection can be a highly valuable and predictive bridge between in vitro drug discovery and early clinical evaluation.