Antibacterial agents in infections of the central nervous system.

Animal models have been invaluable in our understanding of the use of antibacterial agents in the therapy of central nervous system (CNS) infections.(77) Although in vitro susceptibility testing may give information regarding the activity of an antibacterial agent against a bacterial pathogen, the in vivo effectiveness of a drug may be very different. The animal model of meningitis most frequently used for therapeutic studies at the present time is the rabbit model, which uses an intracisternal method for organism inoculation.(16) The intracisternal route of inoculation appears to be the most reliable method for producing experimental meningitis in animals, although there are several disadvantages: (1) the natural route of dissemination to the cerebrospinal fluid (CSF) is bypassed so the pathogenesis is artificial; (2) early bacteremia and death may supervene prior to CSF inflammation; (3) extravasation into the surrounding tissues may occur; (4) direct trauma to the medulla oblongata may result in cardiorespiratory arrest; and (5) anesthetics and analgesics used during experiments may alter the pathophysiology of meningitis by inducing hypotension, hypoventilation, or both. In addition, other predisposing conditions (e.g., history of head trauma, splenectomy, immunosuppression) that may be present in patients with meningitis are not taken into consideration in experimental models; these factors may have significant roles in the pathogenesis of bacterial meningitis.(39) Despite these disadvantages, the intracisternal route of inoculation in the rabbit model is preferred because of easy handling of the animals, relative inexpense, and sufficient CSF volume allows frequent sampling of CSF for quantitative antimicrobial and bacterial concentrations during the treatment period. This model also permits quantitation of the relative penetration of drug into CSF, the effects of meningitis on this entry parameter, and the relative bactericidal efficacy within purulent CSF.