Results from the ARTEMIS DISK Global Antifungal Surveillance Study: a 6.5-year analysis of susceptibilities of Candida and other yeast species to fluconazole and voriconazole by standardized disk diffusion testing

Abstract

Fluconazole in vitro susceptibility test results for 140,767 yeasts were collected from 127 participating investigators in 39 countries from June 1997 through December 2003. Data were collected on 79,343 yeast isolates tested with voriconazole from 2001 through 2003. All investigators tested clinical yeast isolates by the CLSI (formerly NCCLS) M44-A disk diffusion method. Test plates were automatically read and results were recorded with the BIOMIC Vision Image Analysis System. Species, drug, zone diameter, susceptibility category, and quality control results were collected quarterly via e-mail for analysis. Duplicate (the same patient, same species, and same susceptible-resistant biotype profile during any 7-day period) and uncontrolled test results were not analyzed. The 10 most common species of yeasts all showed less resistance to voriconazole than to fluconazole. Candida krusei showed the largest difference, with over 70% resistance to fluconazole and less than 8% to voriconazole. All species of yeasts tested were more susceptible to voriconazole than to fluconazole, assuming proposed interpretive breakpoints of > or =17 mm (susceptible) and < or =13 mm (resistant) for voriconazole. MICs reported in this study were determined from the zone diameter in millimeters from the continuous agar gradient around each disk, which was calibrated with MICs determined from the standard CLSI M27-A2 broth dilution method by balanced-weight regression analysis. The results from this investigation demonstrate the broad spectrum of the azoles for most of the opportunistic yeast pathogens but also highlight several areas where resistance may be progressing and/or where previously rare species may be "emerging."

FIG. 1.

Fluconazole (left) and voriconazole (right) zone diameter (in mm) distribution for all Candida spp.: 79,485 isolates tested against fluconazole and 75,809 isolates tested against voriconazole. The isolates were obtained from 115 institutions in 34 countries from 2001 through 2003. Interpretive breakpoints: S, ≥19 mm (fluconazole) and ≥17 mm (voriconazole); SDD, 15 to 18 mm (fluconazole) and 14 to 16 mm (voriconazole); R, ≤14 mm (fluconazole) and ≤13 mm (voriconazole).

FIG. 2.

Correlation of broth microdilution MICs and disk diffusion zone diameters with Candida (1,670 isolates) and voriconazole. ZD, zone diameter.

FIG. 3.

Cumulative susceptibilities of Candida species to fluconazole and voriconazole using calculated MICs: (A) C. albicans (47,584 isolates [voriconazole]; 49,991 isolates [fluconazole]); (B) C. glabrata (8,719 isolates [voriconazole]; 9,040 isolates [fluconazole]); (C) C. parapsilosis (5,233 isolates [voriconazole]; 5,539 isolates [fluconazole]); (D) C. tropicalis (5,643 isolates [voriconazole]; 5,959 isolates [fluconazole]).