Therapeutic efficacy of caspofungin alone and in combination with amphotericin B deoxycholate for coccidioidomycosis in a mouse model.
OBJECTIVE
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 > or =0.5 and > or =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.
González
Gloria M
GM
Departamento de Microbiología, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León 64460, Mexico. gmglez@yahoo.com.mx
González
Gerardo
G
Najvar
Laura K
LK
Graybill
John R
JR
D000666:Amphotericin B / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D000077336:Caspofungin; D003045:Coccidioides / Q000187:drug effects; D003047:Coccidioidomycosis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality*; D003840:Deoxycholic Acid / Q000627:therapeutic use*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D054714:Echinocandins / Q000627:therapeutic use*; D006801:Humans; D055666:Lipopeptides; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016896:Treatment Outcome
D000935:Antifungal Agents; D004338:Drug Combinations; D054714:Echinocandins; D055666:Lipopeptides; D003840:Deoxycholic Acid; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination; D000077336:Caspofungin