0000000000424458
AUTHOR
Giorgio Scalise
Posaconazole against Candida glabrata Isolates with Various Susceptibilities to Fluconazole
ABSTRACT 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. gl…
Anidulafungin in combination with amphotericin B against Aspergillus fumigatus.
ABSTRACT We investigated the effects of anidulafungin alone and in combination with amphotericin B against Aspergillus fumigatus . Indifference was the only type of interaction observed in vitro. Anidulafungin at 1 and 5 mg/kg of body weight/day, amphotericin B at 1 mg/kg/day, and combination therapy prolonged the survival of mice with invasive aspergillosis. Anidulafungin at 5 mg/kg/day, alone and in combination with amphotericin B, reduced the kidney fungal burden. Overall, the combination was not superior to the most active single drug.
In vitro and in vivo anticryptococcal activities of a new pyrazolo-isothiazole derivative
We investigated the activity of a pyrazolo-isothiazole derivative (G8) against Cryptococcus neoformans. A first screening test showed that G8 at 10 mg/L inhibited the growth of 14 of 15 clinical isolates tested. Killing experiments showed that fungicidal activity was achieved after 8 h of treatment with G8 at concentrations > or =10 mg/L. In a murine model of systemic cryptococcosis, G8 was effective at prolonging survival compared with the controls. Our data indicate that this new derivative has a potential therapeutic role in infections caused by C. neoformans.
Posaconazole Activity against Candida glabrata after Exposure to Caspofungin or Amphotericin B
ABSTRACT We evaluated the effects of sequential therapy with caspofungin (CAS) or amphotericin B (AMB) followed by posaconazole (POS) against Candida glabrata . The susceptibilities to POS of yeast cells pre-exposed to CAS or AMB were identical to those of untreated cells as shown by standard Clinical and Laboratory Standards Institute broth dilution, cell viability, and disk diffusion methods. We then investigated the activity of sequential regimens in an experimental model of disseminated candidiasis. CAS given at 1 mg/kg/day for 2 days followed by POS at either 15 or 30 mg/kg/day significantly reduced the counts compared to the controls, but this treatment was not superior to the use of …
Evaluation of the Disk Diffusion Method Compared to the Microdilution Method in Susceptibility Testing of Anidulafungin against Filamentous Fungi
ABSTRACT Susceptibility testing of anidulafungin (AFG) against 32 mold isolates showed an excellent correlation between disk diffusion (DD) and broth microdilution methods. Based on our data, a 2-μg disk of AFG and a 24-h reading time might represent the best parameters for AFG DD testing against filamentous fungi.
Comparison between Disk Diffusion and Microdilution Methods for Determining Susceptibility of Clinical Fungal Isolates to Caspofungin
ABSTRACT We compared the caspofungin (CAS) susceptibility testing results generated by the disk diffusion (DD) assay with the results of the Clinical and Laboratory Standards Institute (CLSI) broth microdilution (BD) reference method for 106 yeast isolates. The isolates represented 11 different fungal species, including Candida albicans ( n = 50), C. parapsilosis ( n = 10), C. glabrata ( n = 10), C. tropicalis ( n = 10), C. guillermondii ( n = 6), C. rugosa ( n = 5), C. krusei ( n = 5), C. kefyr ( n = 2), C. pelliculosa ( n = 2), Saccharomyces cerevisiae ( n = 3), and Geotrichum candidum ( n = 3). The DD assay was performed in supplemented Mueller-Hinton agar with CAS, which was tested at c…