Posaconazole against Candida glabrata Isolates with Various Susceptibilities to Fluconazole
Autor: | Maria Eleonora Milici, Serena Tomassetti, Giorgio Scalise, Elisabetta Spreghini, Carmelo Massimo Maida, Daniele Giannini, Francesco Barchiesi, Fiorenza Orlando |
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Rok vydání: | 2008 |
Předmět: |
Male
Posaconazole Antifungal Agents Candida glabrata Microbial Sensitivity Tests Drug resistance Biology Kidney Microbiology Mice chemistry.chemical_compound Drug Resistance Fungal hemic and lymphatic diseases Amphotericin B medicine Animals Humans Experimental Therapeutics Pharmacology (medical) Fluconazole Pharmacology Experimental model Candidiasis Fungi imperfecti Triazoles biology.organism_classification Treatment Outcome Infectious Diseases chemistry Caspofungin medicine.drug |
Zdroj: | Antimicrobial Agents and Chemotherapy. 52:1929-1933 |
ISSN: | 1098-6596 0066-4804 |
Popis: | We investigated the in vitro activities of posaconazole (POS), fluconazole (FLC), amphotericin B (AMB), and caspofungin (CAS) against four clinical isolates of Candida glabrata with various susceptibilities to FLC (FLC MICs ranging from 1.0 to >64 μg/ml). POS MICs ranged from ≤0.03 to 0.5 μg/ml; AMB MICs ranged from 0.25 to 2.0 μg/ml, while CAS MICs ranged from 0.03 to 0.25 μg/ml. When FLC MICs increased, so did POS MICs, although we did not observe any isolate with a POS MIC greater than 0.5 μg/ml. Time-kill experiments showed that POS, FLC, and CAS were fungistatic against all isolates, while AMB at eight times the MIC was fungicidal against three out of four isolates of C. glabrata tested. Then, we investigated the activity of POS in an experimental model of disseminated candidiasis using three different isolates of C. glabrata : one susceptible to FLC (S; FLC MICs ranging from 1.0 to 4.0 μg/ml; POS MIC of ≤0.03 μg/ml), one susceptible in a dose-dependent manner (SDD; FLC MICs ranging from 32 to 64 μg/ml; POS MICs ranging from 0.125 to 0.25 μg/ml), and another one resistant to FLC (R; FLC MIC of >64 μg/ml; POS MIC of 0.5 μg/ml). FLC significantly reduced the kidney burden of mice infected with the S strain ( P = 0.0070) but not of those infected with the S-DD and R strains. POS was significantly effective against all three isolates at reducing the kidney fungal burden with respect to the controls ( P ranging from 0.0003 to 0.029). In conclusion, our data suggest that POS may be a useful option in the management of systemic infections caused by C. glabrata . Additionally, the new triazole may be a therapeutic option in those cases where an FLC-resistant isolate is found to retain a relatively low POS MIC. |
Databáze: | OpenAIRE |
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