In vitro and in vivo effects of echinocandins against Candida parapsilosis sensu stricto, Candida orthopsilosis and Candida metapsilosis.
OBJECTIVE
The aim of the present study was to compare, in vitro and in vivo, the effects of caspofungin, micafungin and anidulafungin against Candida parapsilosis complex isolates.


METHODS
In vitro activities of all three echinocandins were assessed against C. parapsilosis sensu stricto (n = 4), Candida orthopsilosis (n = 4) and Candida metapsilosis (n = 3) using broth microdilution susceptibility testing, minimum fungicidal concentration determination and a killing-curve assay, in the absence and in the presence of 50% human serum. Then, the activities of all drugs were investigated in an immunocompromised murine model of systemic candidiasis. Animals were infected with six isolates (two for each species) and treated with the echinocandins administered at 0.25, 1, 5 and 10 mg/kg/day for six consecutive days. Fungal burdens were assessed in kidney tissues on day 7 post-infection.


RESULTS
Geometric mean MICs of caspofungin, micafungin and anidulafungin for C. parapsilosis sensu lato were, respectively, 0.09, 0.14 and 0.20 mg/L without serum, and 0.70, 3.92 and 5.84 mg/L with serum. The fungicidal activity of all three echinocandins was variable; however, the addition of serum reduced the fungicidal effects against these species. In vivo studies showed that caspofungin at 5 and 10 mg/kg/day significantly decreased the kidney burdens with respect to the controls for all isolates, while micafungin was active at 5 and/or 10 mg/kg/day only against C. metapsilosis.


CONCLUSIONS
Our susceptibility testing showed that caspofungin was the most active echinocandin against all three species. Also, caspofungin resulted in significant therapeutic effects for treatments of experimental systemic infections due to the three species, while micafungin was effective only against C. metapsilosis.
Department of Biomedical Sciences and Public Health, Clinic Infectious Disease, Università Politecnica delle Marche, Ancona, Italy. e.spreghini@univpm.it
Elisabetta
E
Spreghini
Fiorenza
F
Orlando
Arianna
A
Tavanti
Sonia
S
Senesi
Daniele
D
Giannini
Esther
E
Manso
Francesco
F
Barchiesi
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002175:Candida / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D054714:Echinocandins / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007668:Kidney / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D016896:Treatment Outcome
D000935:Antifungal Agents; D054714:Echinocandins