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

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 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 (0.8mg/kg/day intraperitoneally and 40mg/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. © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved.