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 Ahmed, A.
Right arrow Articles by McCracken, G. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ahmed, A.
Right arrow Articles by McCracken, G. H., Jr.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, April 1999, p. 876-881, Vol. 43, No. 4
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Pharmacodynamics of Vancomycin for the Treatment of Experimental Penicillin- and Cephalosporin-Resistant Pneumococcal Meningitis

Amina Ahmed,* Hasan Jafri, Irja Lutsar, Cynthia C. McCoig, Monica Trujillo, Loretta Wubbel, Sharon Shelton, and George H. McCracken Jr.

The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

Received 18 June 1997/Returned for modification 7 December 1997/Accepted 20 November 1998

With the emergence of beta -lactam antibiotic resistance among strains of Streptococcus pneumoniae, vancomycin has assumed an important role in the treatment of bacterial meningitis. Using the rabbit meningitis model, we evaluated the pharmacokinetics and pharmacodynamics of vancomycin in this setting. Animals were given 80 mg/kg of body weight daily in two or four divided doses to determine the penetration and activity of vancomycin in cerebrospinal fluid (CSF); each regimen was administered with and without dexamethasone. Mean peak (2 h) concentrations in CSF that were four- to eightfold higher than the minimum bactericidal concentration (MBC; 0.5 µg/ml) for the pathogen were adequate for bacterial clearance. In both groups concentrations in CSF remained higher than the MBC for greater than 80% of the respective dosing intervals, and the penetration of vancomycin into CSF was 20%. Mean concentrations in CSF at 24 to 36 h of therapy were lower than those achieved during the first 12 h, consistent with a decline in the level of antibiotic entry into CSF as inflammation wanes. Rates of bacterial clearance were similar for the two regimens, and for all animals cultures of CSF were sterile by 36 h. The coadministration of dexamethasone significantly reduced the penetration of vancomycin into CSF by 29% and significantly lowered the rate of bacterial clearance during the first 6 h in animals receiving 20-mg/kg doses of vancomycin. For animals receiving 40-mg/kg doses, therapeutic peak concentrations in CSF were obtained even with steroid use, suggesting that the effect of steroids may be circumvented by the use of larger daily doses of vancomycin.

* Corresponding author. Present address: Department of Pediatrics, Carolinas Medical Center, 1000 Blythe Blvd., Medical Education Building, 4th Floor, Charlotte, NC 28232-2861. Phone: (704) 355-1301. Fax: (314) 355-5429. E-mail: aahmed{at}carolinas.org.

Antimicrobial Agents and Chemotherapy, April 1999, p. 876-881, Vol. 43, No. 4
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Nguyen, H. M., Graber, C. J. (2009). Limitations of antibiotic options for invasive infections caused by methicillin-resistant Staphylococcus aureus: is combination therapy the answer?. J Antimicrob Chemother 0: dkp377v1-dkp377 [Abstract] [Full Text]  
  • Lewin, J. J. III, Lapointe, M., Ziai, W. C. (2005). Central Nervous System Infections in the Critically Ill. Journal of Pharmacy Practice 18: 25-41 [Abstract]  
  • Fernandez, A., Cabellos, C., Tubau, F., Maiques, J. M., Domenech, A., Ribes, S., Linares, J., Viladrich, P. F., Gudiol, F. (2005). Experimental study of teicoplanin, alone and in combination, in the therapy of cephalosporin-resistant pneumococcal meningitis. J Antimicrob Chemother 55: 78-83 [Abstract] [Full Text]  
  • Boylan, C. J., Campanale, K., Iversen, P. W., Phillips, D. L., Zeckel, M. L., Parr, T. R. Jr. (2003). Pharmacodynamics of Oritavancin (LY333328) in a Neutropenic-Mouse Thigh Model of Staphylococcus aureus Infection. Antimicrob. Agents Chemother. 47: 1700-1706 [Abstract] [Full Text]  
  • Rodriguez-Cerrato, V., McCoig, C. C., Saavedra, J., Barton, T., Michelow, I. C., Hardy, R. D., Bowlware, K., Iglehart, J., Katz, K., McCracken, G. H. Jr (2003). Garenoxacin (BMS-284756) and Moxifloxacin in Experimental Meningitis Caused by Vancomycin-Tolerant Pneumococci. Antimicrob. Agents Chemother. 47: 211-215 [Abstract] [Full Text]  
  • Lanska, D. J. (2002). Anthrax meningoencephalitis. Neurology 59: 327-334 [Abstract] [Full Text]  
  • Orihuela, C. J., Janssen, R., Robb, C. W., Watson, D. A., Niesel, D. W. (2000). Peritoneal Culture Alters Streptococcus pneumoniae Protein Profiles and Virulence Properties. Infect. Immun. 68: 6082-6086 [Abstract] [Full Text]  
  • Harwell, J. I., Brown, R. B. (2000). The Drug-Resistant Pneumococcus: Clinical Relevance, Therapy, and Prevention. Chest 117: 530-541 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»