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JAC Advance Access originally published online on March 5, 2007
Journal of Antimicrobial Chemotherapy 2007 59(4):791-793; doi:10.1093/jac/dkl550
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Flucytosine therapeutic monitoring: 15 years experience from the UK

A. C. Pasqualotto1, S. J. Howard1,2, C. B. Moore2 and D. W. Denning1,2,*

1 School of Medicine, The University of Manchester and Wythenshawe Hospital, Manchester, UK 2 The Regional Mycology Laboratory, Wythenshawe Hospital, Manchester, UK

Received 21 September 2006; returned 19 November 2006; revised 18 December 2006; accepted 20 December 2006

* Correspondence address. Education and Research Centre, Wythenshawe Hospital, Southmoor Road, Manchester M23 9LT, UK. Tel: +44-(0)161-291-5811; Fax: +44-(0)161-291-5806; E-mail: ddenning{at}manchester.ac.uk

Background: There is uniform consensus that flucytosine blood concentrations should be measured to avoid toxicity and ensure adequate efficacy.

Objectives and methods: The purpose of this study was to evaluate all flucytosine levels performed in a regional centre in the UK from October 1991 to May 2006. Concentrations were measured by bioassay.

Results: We reviewed 1071 flucytosine levels in 233 patients, including 33 neonates. Overall, only 20.5% of levels were in the expected therapeutic range. Low levels were observed in 40.5%, of which 5.1% were undetectable levels (<12.5 mg/L). High levels occurred in 38.9%, of which 9.9% were considered potentially toxic (>100 mg/L). High flucytosine levels occurred more frequently amongst neonates, which could be related to an immature renal system resulting in drug accumulation.

Conclusions: Our findings reveal that the vast majority of patients were out of range for flucytosine levels. These data emphasize the importance of monitoring flucytosine levels.

Keywords: drug monitoring , Candida , Cryptococcus , bioassay


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