Models of Experimental Bacterial Meningitis. Role and Limitations

The seriousness of bacterial meningitis has encouraged the development of animal models that characterize complex pathogenetic and pathophysiologic mechanisms, provide evaluation of pharmacokinetic and antimicrobial effects of antibiotics (especially since the worldwide emergence of multiresistant bacteria), and establish new adjuvant treatment strategies (e.g., use of anti-inflammatory agents). The information obtained from an animal model depends on the site of inoculation. For example, using intranasal, intravenous, subcutaneous, or intraperitoneal inoculation, it is the bacterial and host factors 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 cerebrospinal fluid can reliably produce lethal infections over a predictable time course. Furthermore, because adult animals will not reliably develop meningitis after intranasal or intraperitoneal challenge, infant animals are used. Because these models bypass the natural dissemination of bacteria from the intravascular compartment to the central nervous system, the pathogenesis is artificial. These models, however, are extremely useful for the study of 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 stimulated by findings obtained from these animal models.