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JAC Advance Access published online on September 3, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm332
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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

Caspofungin in vitro and in vivo activity against Brazilian Pythium insidiosum strains isolated from animals

Daniela Isabel Brayer Pereira1, Janio Morais Santurio1,*, Sydney Hartz Alves1, Juliana Siqueira Argenta1, Luciana Pötter2, Andréia Spanamberg3 and Laerte Ferreiro3

1 Laboratório de Pesquisas Micológicas, Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Maria, Campus Universitário, Prédio 20, 4139, 97105900 Santa Maria, RS, Brazil 2 Departamento de Zootecnia, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil 3 Faculdade de Medicina Veterinária, Departamento de Patologia Clínica Veterinária, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

Received 11 May 2007; returned 5 July 2007; revised 3 August 2007; accepted 6 August 2007

* Corresponding author. Tel/Fax: +55-55-32208906; E-mail: santurio{at}smail.ufsm.br

Objectives: The present study evaluated the susceptibility of 27 clinical isolates of Pythium insidiosum to caspofungin in vitro and correlated the results with the therapeutic response in vivo in rabbits with experimental pythiosis.

Methods: The macrodilution method was performed in accordance with the CLSI document M38-A technique. Three reading criteria for MICs were adopted: MIC0, MIC1 and MIC2 (100%, 90% and 50% growth inhibition, respectively). The minimum fungicidal concentration was also determined. Ten rabbits inoculated with viable P. insidiosum zoospores were divided into two groups: group 1 (control) and group 2 (treated with caspofungin at a dosage of 1 mg/kg/day for 20 consecutive days).

Results: Of the isolates 51.8% had an MIC0 of 64 mg/L, 88.8% of isolates had an MIC1 between 8 and 64 mg/L and 62.9% of isolates had a minimum fungicidal concentration of 64 mg/L. In the in vivo assay, growth of subcutaneous lesions reduced during treatment, but rapidly resumed when treatment was stopped.

Conclusions: The results showed that caspofungin has limited fungistatic activity against P. insidiosum. This work is the first study to analyse the susceptibility of this oomycete to inhibitors of ß-glucans of the cellular wall.

Key Words: pythiosis , oomycete , susceptibility


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