In vitro and in vivo effects of echinocandins against Candida parapsilosis sensu stricto, Candida orthopsilosis and Candida metapsilosis

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. In vitro activities of all three echinocandins were assessed against C. parapsilosis sensu stricto (n = 4), Candida orthopsilosis...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2012-09, Vol.67 (9), p.2195-2202
Main Authors: Spreghini, Elisabetta, Orlando, Fiorenza, Tavanti, Arianna, Senesi, Sonia, Giannini, Daniele, Manso, Esther, Barchiesi, Francesco
Format: Article
Language:English
Subjects:
Animal models
Animals
Antifungal Agents - pharmacology
Antifungal Agents - therapeutic use
Candida
Candida - drug effects
Candida parapsilosis
Candidiasis
Candidiasis - drug therapy
Candidiasis - microbiology
Caspofungin
Chemotherapy
Colony Count, Microbial
Disease Models, Animal
Disseminated infection
Drugs
echinocandins
Echinocandins - pharmacology
Echinocandins - therapeutic use
Female
Fungi
Fungicidal activity
Humans
Immunocompromised Host
Infectious diseases
Kidney
Kidney - microbiology
micafungin
Mice
Microbial Sensitivity Tests
Microbial Viability - drug effects
Minimum inhibitory concentration
Pharmaceuticals
Treatment Outcome
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Summary: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. 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. 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. 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.
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dks180