Journal Article

A novel murine model of cerebral scedosporiosis: lack of efficacy of amphotericin B

Javier Capilla, Emilio Mayayo, Carolina Serena, F. Javier Pastor and Josep Guarro

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 54, issue 6, pages 1092-1095
Published in print December 2004 | ISSN: 0305-7453
Published online December 2004 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dkh468
A novel murine model of cerebral scedosporiosis: lack of efficacy of amphotericin B

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Objectives: Cerebral scedosporiosis is a life-threatening infection that is difficult to treat. The aim of this work was to develop a murine model of cerebral infection by Scedosporium apiospermum using intracranial inoculation and to use this model to evaluate the efficacy of amphotericin B deoxycholate and liposomal amphotericin B.

Methods: Mice were rendered neutropenic by intraperitoneal cyclophosphamide and intravenous (iv) 5-fluorouracil administration. Animals were infected with iv or intracranial inoculation of 1×104, 5×104 or 5×105 cfu of a clinical strain of S. apiospermum. Tissue burden reduction was determined in kidneys and brain 4 days after the infection. Efficacy of amphotericin B and liposomal amphotericin B (0.8 mg/kg/day intraperitoneally and 40 mg/kg/day iv, respectively) was evaluated in neutropenic mice infected iv or intracranially with 5×104 cfu. Survival was analysed with the log-rank test. Fungal burden values of different groups were compared using the Mann–Whitney U-test.

Results: In our model, intracranial infection produced a higher fungal load in the brain and a lower fungal load in the kidney than iv inoculation. Survival of animals infected intracranially and treated with amphotericin B or liposomal amphotericin B (mean survival time = 8.3 and 9.2 days, respectively) was not different from the control group (P=0.58 and 0.85, respectively).

Conclusions: We have developed a murine model of cerebral scedosporiosis, which may be useful for studying various pathological aspects of this infection and evaluating new therapeutic approaches. Amphotericin B and liposomal amphotericin B were unable to resolve the infection.

Keywords: Scedosporium apiospermum; brain infections; animal models

Journal Article.  2236 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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