Pharmacokinetics and pharmacodynamics of anidulafungin for Candida endophalmitis Further evidence for the utility of Echinocandins for treatment of a rapidly sight-threatening infection

Ref ID: 17730

Author:

J.L. Livermore*, P.A. Warn, S. Howard, J. Goodwin, L. Gregson,
A. Sharp, T. Felton, J. Abbott, W. Hope

Author address:

Manchester, London, UK)

Full conference title:

22nd European Congress of Clinical Microbiology and Infectious Diseases

Abstract:

Objectives: Endogenous Candida endophthalmitis involving the
chorioretinal structures with or without the vitreous humour (VH) is a
rapidly sight-threatening infection and a common complication of
candidemia. IDSA guidelines recommend amphotericin B deoxycholate
(dAmB) and oral flucytosine for severe disease or fluconazole for less
severe cases. The utility of the echinocandins for the treatment of
Candida endophthalmitis is unknown. The objective of this study was
to investigate the in vivo pharmacokinetics and pharmacodynamics of
anidulafungin for treatment of Candida endophthalmitis.
Methods: A well-validated rabbit model of endogenous Candida
endophthalmitis was used. Jugular vein catheters attached to a
subcutaneous port were surgically implanted under general anaesthesia.
Candida albicans strain ATCC MYA 1237 (1 · 106 CFU/rabbit) was
injected via the port and anidulafungin (5, 10, 20 mg/kg) or saline was
administered via the same route at 48 and 72 hours post infection. Rabbits
were sacrificed at predefined time points 0-96 hours post inoculation.
Aquous and vitreous humour were retrieved, homogenised and submitted
for quantitative culture. Concentrations of anidulafungin in plasma and
within the eye were assessed using HPLC. A mathematical model was
used to link plasma and intraocular concentrations with the observed
antifungal effect.
Results: There was progressive logarithmic growth of Candida in
vitreous humour in the 96 hours. Control rabbits showed a maximal
fungal burden of approx. log10 CFU/mL four in the vitreous humour.
Anidulafungin penetrated the vitreous humour and aqueous humour in a
dose-dependent manner, and the pharmacokinetics were linear. There
was a dose-dependent decline in the fungal density within the vitreous
humour with near-maximal reduction observed with a daily dosage of
10-20 mg/kg. The pharmacokinetic and pharmacodynamic data were
well explained by the mathematical model.
Conclusion: Anidulafungin penetrates the eye and causes a dosedependent
decline in fungal density in the eye. The mathematical model
can be used to define human dosages that are associated with near
maximal antifungal activity and therefore appropriate regimens for
clinical use.

Abstract Number: NULL

Conference Year: 2012

Link to conference website: NULL

New link: NULL

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