Pharmacodynamics of antibiotics in the therapy of meningitis: infection model observations

Schmidt, T; Täuber, MG (1993). Pharmacodynamics of antibiotics in the therapy of meningitis: infection model observations. Journal of antimicrobial chemotherapy, 31 Suppl D(31), pp. 61-70. Oxford: Oxford University Press 10.1093/jac/31.suppl_D.61

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Detailed studies of pharmacodynamic principles relevant to the therapy of bacterial meningitis are difficult to perform in man, while the rabbit model of bacterial meningitis has proved to be extremely valuable and has led to insights that appear relevant for the treatment of humans. Most importantly in the light of the restricted penetration of antibiotics into the CSF, animal studies have shown that in meningitis there is a dose-response curve between the CSF concentrations achieved by antibiotics and their bactericidal activity. This appears to be true for all classes of antibiotics thus far examined, including the beta-lactams, which do not show such a dose-response behaviour in other infections. Only CSF concentrations that exceed the MBC of the infecting organism by at least 10-30-fold achieve consistent and rapid bactericidal activity. Such rapid bactericidal activity is a requirement for successful therapy with beta-lactams and can be impaired with certain antibiotics by the specific conditions in infected CSF (protein content; acidic pH; slow-growing bacteria). However, rapid antibiotic killing of the infecting organisms may not be without adverse effects either. Some antibiotics, particularly beta-lactams lead to the brisk liberation of bacterial cell wall components (e.g. endotoxin, in the case of Gram-negative organisms) which have an inflammatory effect on the host and can lead to a temporary deterioration of the disease. Dexamethasone, when administered with the antibiotic, can prevent some of the adverse effects of rapid bacterial lysis.

Item Type:

Journal Article (Further Contribution)

Division/Institute:

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

UniBE Contributor:

Täuber, Martin G.

ISSN:

0305-7453

ISBN:

8335525

Publisher:

Oxford University Press

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:00

Last Modified:

08 Jun 2016 10:44

Publisher DOI:

10.1093/jac/31.suppl_D.61

PubMed ID:

8335525

Web of Science ID:

A1993LF61400007

URI:

https://boris.unibe.ch/id/eprint/25791 (FactScience: 60951)

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