General principles of therapy of pyogenic meningitis

Täuber, MG; Sande, MA (1990). General principles of therapy of pyogenic meningitis. Infectious disease clinics of North America, 4(4), pp. 661-76. New York, N.Y.: Elsevier

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In bacterial meningitis, several pharmacodynamic factors determine therapeutic success-when defined as sterilization of the CSF: (1) Local host defense deficits in the CNS require the use of bactericidal antibiotics to sterilize the CSF. (2) CSF antibiotic concentrations that are at least 10-fold above the MBC are necessary for maximal bactericidal activity. Protein binding, low pH, and slow bacterial growth rates are among the factors that may explain the high antibiotic concentrations necessary in vivo. (3) High CSF peak concentrations that lead to rapid bacterial killing appear more important than prolonged suprainhibitory concentrations, probably because very low residual levels in the CSF prevent bacterial regrowth, even during relatively long dosing intervals. (4) Penetration of antibiotics into the CSF is significantly impaired by the blood-brain barrier and thus, very high serum levels are necessary to achieve the CSF concentrations required for optimal bactericidal activity. Beyond these principles, recent data suggests that rapid lytic killing of bacteria in the CSF may have harmful effects on the brain because of the release of biologically active products from the lysed bacteria. Since rapid CSF sterilization remains a key therapeutic goal, the harmful consequences of bacterial lysis present a major challenge in the therapy of bacterial meningitis. Currently, dexamethasone represents that only clinically beneficial approach to reduce the harmful effects of bacterial lysis, and novel approaches are required to improve the outcome of this serious infection.

Item Type:

Journal Article (Further Contribution)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

UniBE Contributor:

Täuber, Martin G.

ISSN:

0891-5520

ISBN:

2277194

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:00

Last Modified:

04 May 2014 23:17

PubMed ID:

2277194

URI:

https://boris.unibe.ch/id/eprint/25802 (FactScience: 60977)

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