A novel murine model of cerebral scedosporiosis: lack of efficacy of amphotericin B.
OBJECTIVE
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.
Capilla
Javier
J
Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, 43201 Reus, Spain.
Mayayo
Emilio
E
Serena
Carolina
C
Pastor
F Javier
FJ
Guarro
Josep
J
D000666:Amphotericin B / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001921:Brain / Q000382:microbiology / Q000473:pathology; D001927:Brain Diseases / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008271:Mycetoma / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D009503:Neutropenia; D021681:Scedosporium / Q000187:drug effects* / Q000472:pathogenicity; D017211:Treatment Failure
D000935:Antifungal Agents; D008081:Liposomes; D000666:Amphotericin B