Models of experimental bacterial meningitis - Role and limitations

The seriousness of bacterial meningitis has encouraged the development of a nimal models that characterize complex pathogenetic and pathophysiologic me chanisms, provide evaluation of pharmacokinetic and antimicrobial effects o f antibiotics (especially since the worldwide emergence of multiresistant b acteria), and establish new adjuvant treatment strategies (e.g., use of ant iinflammatory agents). The information obtained from an animal model depend s on the site of inoculation. For example, using intranasal, intravenous, s ubcutaneous, or intraperitoneal inoculation, it is the bacterial and host f actors that determine the development of bacteremia and the potential for a pathogen to invade the central nervous system that primarily are studied. In contrast, experimental models using direct inoculation into the cerebros pinal fluid can reliably produce lethal infections over a predictable time course. Furthermore, because adult animals will not reliably develop mening itis after intranasal or intraperitoneal challenge, infant animals are used . Because these models bypass the natural dissemination of bacteria from th e intravascular compartment to the central nervous system, the pathogenesis is artificial. These models, however, are extremely useful for the study o f pathogen and host factors leading to meningeal inflammation and resulting complications, and for evaluating potentially useful agents for treatment therapy During the past decade, the design of clinical studies has been sti mulated by findings obtained from these animal models.