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JAC Advance Access published online on October 27, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh468
© 2004 by The British Society for Antimicrobial Chemotherapy
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Original article

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

Javier Capilla 1, Emilio Mayayo 2, Carolina Serena 1, F. Javier Pastor 1, and Josep Guarro 1*

1 Unitat de Microbiologia, Facultat de Medicina i Ciencies de la Salut, Universitat Rovira i Virgili, Reus, Spain
2 Unitat d'Anatomia Patòlogica, Facultat de Medicina i Ciencies de la Salut, Universitat Rovira i Virgili, Reus, Spain

* To whom correspondence should be addressed.
Josep Guarro, E-mail: umb{at}fmcs.urv.es


  Abstract

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 1x104, 5x104 or 5x105 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 5x104 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.
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