Background: Cerebral aspergi[[osis is associated with an unacceptably high mortality despite antifunga[ treatment. Objectives: To compare the efficacy of caspofungin combined with [iposoma[ amphotericin B vs. caspofungin alone for the treatment of cerebral aspergi[[osis in immunocompetent nursing rats. Methods: ELeven-day-oLd non-immunosuppressed Wistar Wl rats were infected by intracisterna[ injection of 10pL of a conidia[ suspension of Aspergi[[ us fumigatus. Treatment started 18h after infection and was given for 10 days. Regimens were caspofungin 1 mg/kg/d i.p. (n=20) and [iposoma[ amphotericin B 5 mg/kg/d + caspofungin lmg/kg/d i.p. (n= 21).lnfected controls (n=14) were given NaC[ 0.9% or glucose 5% i.p. Results: ControLs consistently showed symptoms of cerebra[ AsperBillus infection. Their mean survival time was 4.4 days. Treatment significantly increased survival time to 10.5 and 9.3 days for caspofungin alone and caspofungin combined with amphotericin B, respectively. The difference between treatment regimens was not significant. CNS fungus burden determined by culture of cortical homogenates declined over time; interestingLy, there was no significant difference between controts and treated animals. Two animals in each treatment group had sterile brain cultures. Funga[ dissemination determined by culture of kidney homogenates was found in 7/14 controls, 0/20 animals treated with caspofungin, and 1/21 animals of the combination group. Conclusion: Caspofungin atone and in combination with [iposoma[ amphotericin B significantly increases survival time in a Lethal mode[ of cerebra[ aspergi[[osis. RemarkabLy, CNS fungus burden did not differ between controls and treated animals. The hypothesis that antifunga[ treatment may result in a decreased inflammatory reaction is being further investigated.
Full conference title:
14th International Symposium of Infections in the Immunocompromised Host
- ISIIH, 14th