JAC Advance Access published online on October 12, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm383
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Therapeutic efficacy of caspofungin alone and in combination with amphotericin B deoxycholate for coccidioidomycosis in a mouse model
1 Departamento de Microbiología, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León 64460, Mexico 2 Hospital Universitario, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León 64460, Mexico 3 Department of Medicine, Division of Infectious Diseases, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA
Received 20 January 2007; returned 17 February 2007; revised 11 September 2007; accepted 13 September 2007
* Corresponding author. Tel: +1-5281-8329-4166; Fax: +1-5281-8348-5477; E-mail: gmglez{at}yahoo.com.mx
Objectives: The therapeutic efficacy of caspofungin alone and in combination with amphotericin B deoxycholate was evaluated in treatment of murine coccidioidomycosis.
Methods: Survival and tissue burdens of the spleens and livers were used as antifungal response markers. In a monotherapy study, caspofungin was injected intraperitoneally at 0.1, 0.2, 0.5, 1 and 5 mg/kg per day on days 2 through 15. Amphotericin B deoxycholate was given at 0.1, 0.2 and 0.5 mg/kg intravenously and 1 and 5 mg/kg intraperitoneally three times per week for 2 weeks. In a combination therapy study, amphotericin B deoxycholate at 0.1 mg/kg was administered intravenously three times per week for 2 weeks, respectively, with and without caspofungin intraperitoneally given at 0.1, 0.5 and 5 mg/kg daily on days 2 through 15 post-infection.
Results: The study shows that caspofungin and amphotericin B deoxycholate at 
0.5 and 0.1 mg/kg, respectively, were significant in both prolongation of survival and reduction of the tissue fungal burdens of mice compared with controls. No sterilization of either organ was observed with caspofungin doses. In combination therapy, any combination of caspofungin (0.1, 0.5 and 5 mg/kg) with amphotericin B deoxycholate (0.1 mg/kg) improved the period of survival and significantly reduced spleen and liver counts compared with controls.
Conclusions: This study indicates that caspofungin has efficacy against systemic coccidioidomycosis in a murine model given in combination with amphotericin B deoxycholate.
Key Words: combination therapy , AMB , echinocandins