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Antimicrobial Agents and Chemotherapy, October 2007, p. 3760-3762, Vol. 51, No. 10
0066-4804/07/$08.00+0     doi:10.1128/AAC.00488-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Optimization of the Dosage of Flucytosine in Combination with Amphotericin B for Disseminated Candidiasis: a Pharmacodynamic Rationale for Reduced Dosing{triangledown}

William W. Hope,1,2,3* Peter A. Warn,1 Andrew Sharp,1 Paul Reed,4 Brian Keevil,5 Arnold Louie,2 Thomas J. Walsh,3 David W. Denning,1 and George L. Drusano2

Department of Medicine, The University of Manchester, 1.800 Stopford Building, Oxford Road, Manchester M13 9PT, United Kingdom,1 Ordway Research Institute, 150 New Scotland Avenue, Albany, New York 12208,2 Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892,3 Department of Biochemistry, Hope Hospital, Salford, Manchester M6 8HD, United Kingdom,4 Department of Biochemistry, Wythenshawe Hospital, Southmoor Road, Manchester M23 9LT, United Kingdom5

Received 11 April 2007/ Returned for modification 27 May 2007/ Accepted 27 July 2007

Amphotericin B and flucytosine (5FC) have an additive effect when used for disseminated candidiasis. Here, we bridge the results of an experimental pharmacodynamic study to humans and demonstrate that a 5FC dosage of 25 mg/kg of body weight/day in four divided doses in combination with amphotericin B produces near-maximal effect.

* Corresponding author. Mailing address: Department of Medicine, The University of Manchester, 1.800 Stopford Building, Oxford Road, Manchester M13 9PT, United Kingdom. Phone: 44 (0)161 275 3918. Fax: 44 (0)275 5656. E-mail: william.hope{at}manchester.ac.uk

{triangledown} Published ahead of print on 6 August 2007.

Antimicrobial Agents and Chemotherapy, October 2007, p. 3760-3762, Vol. 51, No. 10
0066-4804/07/$08.00+0     doi:10.1128/AAC.00488-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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