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 Google Scholar
Google Scholar
Right arrow Articles by Brouwer, A. E.
Right arrow Articles by Harrison, T. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brouwer, A. E.
Right arrow Articles by Harrison, T. S.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, March 2007, p. 1038-1042, Vol. 51, No. 3
0066-4804/07/$08.00+0     doi:10.1128/AAC.01188-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Oral versus Intravenous Flucytosine in Patients with Human Immunodeficiency Virus-Associated Cryptococcal Meningitis{triangledown}

Annemarie E. Brouwer,1,2,3 Hendrikus J. M. van Kan,4 Elizabeth Johnson,5 Adul Rajanuwong,6 Prapit Teparrukkul,6 Vannaporn Wuthiekanun,2 Wirongrong Chierakul,2 Nick Day,2,7 and Thomas S. Harrison1*

Centre for Infection, St. George's University of London, United Kingdom,1 Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand,2 Department of Internal Medicine and Nijmegen University Centre for Infectious Diseases, University Medical Centre Nijmegen, The Netherlands,3 Department of Clinical Pharmacy, Academic Medical Centre, Amsterdam, The Netherlands,4 Mycology Reference Laboratory, Health Protection Agency South-West Regional Laboratory, Bristol, United Kingdom,5 Department of Medicine, Sappasithiprasong Hospital, Ubon Ratchathani, Thailand,6 Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom7

Received 22 September 2006/ Returned for modification 16 October 2006/ Accepted 17 December 2006

In a randomized controlled trial of amphotericin B-based therapy for human immunodeficiency virus (HIV)-associated cryptococcal meningitis in Thailand, we also compared the mycological efficacy, toxicity, and pharmacokinetics of oral versus intravenous flucytosine at 100 mg/kg of body weight/day for the initial 2 weeks. Half of 32 patients assigned to the two arms containing flucytosine were randomized to oral and half to intravenous flucytosine. Early fungicidal activity was determined from serial quantitative cultures of cerebrospinal fluid (CSF), and toxicity was assessed by clinical and laboratory monitoring. Flucytosine and fluorouracil concentrations in plasma and CSF were measured by high-performance liquid chromatography. No significant bone marrow or hepatotoxicity was seen, there was no detectable difference in bone marrow toxicity between patients on intravenous and those on oral formulation, and no patients discontinued treatment. In patients receiving intravenous flucytosine, the median 24-h area under the concentration-time curve was significantly higher than in the oral group. Despite this difference, there was no difference in early fungicidal activity between patients on intravenous compared with patients on oral flucytosine. The results suggest that either formulation can be used safely at this dosage in a developing country setting, without drug concentration monitoring. The bioavailability of the oral formulation may be reduced in late-stage HIV-infected patients in Thailand. Concentrations of flucytosine with intravenous formulation at 100 mg/kg/day may be in excess of those required for maximal fungicidal activity.

* Corresponding author. Mailing address: Centre of Infection, St George's University of London, London SW17 ORE, United Kingdom. Phone: 44 20 8725 0447. Fax: 44 20 8725 3487. E-mail: tharriso{at}sgul.ac.uk.

{triangledown} Published ahead of print on 28 December 2006.

Antimicrobial Agents and Chemotherapy, March 2007, p. 1038-1042, Vol. 51, No. 3
0066-4804/07/$08.00+0     doi:10.1128/AAC.01188-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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