AAC
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gerber, J.
Right arrow Articles by Nau, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gerber, J.
Right arrow Articles by Nau, R.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, April 2003, p. 1313-1317, Vol. 47, No. 4
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.4.1313-1317.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Rifampin Followed by Ceftriaxone for Experimental Meningitis Decreases Lipoteichoic Acid Concentrations in Cerebrospinal Fluid and Reduces Neuronal Damage in Comparison to Ceftriaxone Alone

Joachim Gerber, Karin Pohl, Valeska Sander, Stephanie Bunkowski, and Roland Nau*

Department of Neurology, Georg-August University, Göttingen, Germany

Received 16 August 2002/ Returned for modification 24 November 2002/ Accepted 13 January 2003

Rifampin (RIF) releases smaller quantities of lipoteichoic acids (LTAs) from Streptococcus pneumoniae than ceftriaxone (CRO). Due to the rapid development of resistance, RIF cannot be used as a single agent for therapy of bacterial meningitis. For this reason, we compared the effect of treatment with RIF followed by treatment with CRO (RIF-CRO) or the effect of treatment with clindamycin (CLI) followed by treatment with CRO (CLI-CRO) to that of CRO alone on the concentrations of LTAs and teichoic acids in vitro. The effects of RIF-CRO on LTA concentrations in cerebrospinal fluid (CSF) and on neuronal injury were investigated in a rabbit model of S. pneumoniae meningitis. In vitro, bacterial titers were effectively reduced by CRO, RIF-CRO, and CLI-CRO when each drug was used at 10 µg/ml. The levels of release of LTAs after the initiation of therapy were lower in RIF-CRO- and CLI-CRO-treated cultures than in cultures treated with CRO alone (P < 0.05 from 3 to 12 h after initiation of treatment). Similarly, in rabbits, the increase in the amount of LTAs in CSF was lower in RIF-CRO-treated animals than in CRO-treated animals (P = 0.02). The density of dentate apoptotic granular cells was lower after RIF-CRO therapy than after CRO therapy (medians, 58.4 and 145.6/mm2, respectively; 25th quartiles, 36.3 and 81.7/mm2, respectively; 75th quartiles, 100.7 and 152.3/mm2, respectively; P = 0.03). Therefore, initiation of therapy with a protein synthesis-inhibiting antibacterial and continuation of therapy with a combination that includes a ß-lactam may be a strategy to decrease neuronal injury in bacterial meningitis.

* Corresponding author. Mailing address: Neurologische Universitätsklinik, Robert-Koch-Straße 40, D-37075 Göttingen, Germany. Phone: 01149-551-398455. Fax: 01149-551-398405. E-mail: rnau{at}gwdg.de.

Antimicrobial Agents and Chemotherapy, April 2003, p. 1313-1317, Vol. 47, No. 4
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.4.1313-1317.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Clin. Vaccine Immunol. Clin. Microbiol. Rev.
J. Clin. Microbiol. ALL ASM JOURNALS

Copyright © 2003 by the American Society for Microbiology. All rights reserved.