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Antimicrobial Agents and Chemotherapy, June 2008, p. 1929-1933, Vol. 52, No. 6
0066-4804/08/$08.00+0     doi:10.1128/AAC.00130-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Posaconazole against Candida glabrata Isolates with Various Susceptibilities to Fluconazole

Istituto di Malattie Infettive e Medicina Pubblica,¹ Centro di Gestione Presidenza Medicina e Chirurgia, Università Politecnica delle Marche,⁴ Dipartimento Ricerche Gerontologiche e Geriatriche N. Masera, I.N.R.C.A. I.R.R.C.S., Ancona,³ Dipartimento di Igiene e Microbiologia D'Alessandro, Università degli Studi di Palermo, Palermo, Italy²

Received 30 January 2008/ Returned for modification 2 March 2008/ Accepted 29 March 2008

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.

Published ahead of print on 7 April 2008.