Journal article
ANTIBACTERIAL AGENTS IN INFECTIONS OF THE CENTRAL NERVOUS SYSTEM
Infectious disease clinics of North America, v 14(2), pp 391-408
2000
PMID: 10829262
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Animal models have been invaluable in our understanding of the use of antibacterial agents in the therapy of central nervous system (CNS) infections.
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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.
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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.
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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.
It is beyond the scope of this article to review the use of antibacterial agents in the therapy of all CNS infections. Therefore, we focus on meningitis (for which there is the most experimental and clinical data) and review the basic therapeutic principles for use of antibacterials in this infection and give recommendations for specific antibacterial agents for therapy in patients with bacterial meningitis.
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Details
- Title
- ANTIBACTERIAL AGENTS IN INFECTIONS OF THE CENTRAL NERVOUS SYSTEM
- Creators
- Mashiul H. Chowdhury - Division of Infectious Diseases (MHC)Allan R. Tunkel - Drexel University
- Publication Details
- Infectious disease clinics of North America, v 14(2), pp 391-408
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)
- Web of Science ID
- WOS:000087196900009
- Scopus ID
- 2-s2.0-0034030510
- Other Identifier
- 991019346723504721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Immunology
- Infectious Diseases