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 x 10(4), 5 x 10(4) or 5 x 10(5) 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 x 10(4) 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.

• Authors: Javier Capilla, Emilio Mayayo, Carolina Serena, F Javier Pastor, Josep Guarro
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 54 Issue 6 Pg. 1092-5 (Dec 2004) ISSN: 0305-7453 [Print] England
• PMID: 15509616 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antifungal Agents
• Liposomes
• Amphotericin B

Topics

• Amphotericin B (administration & dosage, therapeutic use)
• Animals
• Antifungal Agents (administration & dosage, therapeutic use)
• Brain (microbiology, pathology)
• Brain Diseases (drug therapy, microbiology, mortality, pathology)
• Disease Models, Animal
• Humans
• Liposomes (administration & dosage, therapeutic use)
• Male
• Mice
• Mycetoma (drug therapy, microbiology, mortality, pathology)
• Neutropenia
• Scedosporium (drug effects, pathogenicity)
• Treatment Failure