Efficacy of caspofungin and posaconazole in a murine model of disseminated Exophiala infection.
Disseminated phaeohyphomycosis is an uncommon infection affecting immunocompetent and immunocompromised individuals in which response to older antifungal agents has been variable. We compared the effect of six days of therapy with caspofungin, posaconazole, and amphotericin B in parallel studies of survival and fungal burden in an immunocompromised mouse model of Exophiala infection. Mice immunocompromised with cyclophosphamide were treated for 6 days starting one day after initiation of infection. Treatment regimens included amphotericin B, caspofungin, and posaconazole. In the survival studies, experimental animals were observed for 14 days. In the fungal burden tests the experimental animals were sacrificed 7 days after infection and brain and kidney burden determined. Treatment with any agent decreased mortality (P < 0.05), with 40%, 30%, and 80% observed survival of the animals treated with amphotericin B, caspofungin, and posaconazole, respectively. Amphotericin B and posaconazole treatment resulted in a decrease in fungal burden compared to untreated controls (P < 0.05). No reduction in fungal burden was noted in the caspofungin group. All three antifungals evaluated improved survival of immunocompromised mice in this otherwise fatal disseminated phaeohyphomycosis. Amphotericin B and posaconazole reduced fungal burden. Posaconazole and caspofungin appear to have potential for use in treatment of this rare infection.
Rivard
Robert G
RG
Department of Medicine, Brooke Army Medical Center Fort Sam Houston, Texas 78234, USA.
McCall
Suzanne
S
Griffith
Matthew E
ME
Hawley
Joshua S
JS
Ressner
Roseanne A
RA
Borra
Himabindu
H
Moon
James E
JE
Beckius
Miriam L
ML
Murray
Clinton K
CK
Hospenthal
Duane R
DR
D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001921:Brain / Q000382:microbiology; D000077336:Caspofungin; D004195:Disease Models, Animal; D054714:Echinocandins / Q000494:pharmacology*; D005093:Exophiala / Q000254:growth & development*; D005260:Female; D016867:Immunocompromised Host; D007668:Kidney / Q000382:microbiology; D055666:Lipopeptides; D051379:Mice; D008813:Mice, Inbred ICR; D009181:Mycoses / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D016019:Survival Analysis; D014230:Triazoles / Q000494:pharmacology*
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D014230:Triazoles; C101425:posaconazole; D000666:Amphotericin B; D000077336:Caspofungin