Murine models of pneumococcal pneumonia and their applicability to the study of tissue-directed antimicrobials.

Abstract

Animal models have long played a crucial role in the preclinical and postmarketing evaluation of antimicrobial drug efficacy. With the alarming rise of antibiotic resistance in Streptococcus pneumoniae, such models have received increased attention as tools for deriving pharmacodynamic data and for determining the clinical significance of drug resistance. This information helps us to make therapeutic decisions to optimize efficacy and restrict the further promotion of drug resistance. Until now, however, insufficient attention has been paid to the special issues that arise in the evaluation of antimicrobials that are concentrated in tissue relative to serum or plasma. This article reviews the utility of animal models in the evaluation of these tissue-directed antibiotics, citing recent attempts to use murine models of pneumococcal pneumonia to determine the importance of macrolide resistance. A promising new, low-dose aerosol model of pneumonia is briefly presented, as is a discussion of the limitations of existing models.