Zone Diameter Interpretive Standards, Corresponding Minimal

Inhibitory Concentration (MIC) Interpretive Breakpoints, and

Quality Control Limits for Antifungal Disk Diffusion Susceptibility
Testing of Yeasts; Third Informational Supplement

Table 1. Zone Diameter Interpretive Standards and Corresponding Minimal Inhibitory

Concentration (MIC) Breakpoints for Select Antifungal Agents Against Candida spp.1-7
Zone Diameter, Nearest Whole (mm) Equivalent MIC Breakpoints (μg/mL)
Antifungal Disk
Agent Content S* S-DD* R* NS* S* S-DD* R* NS*

Caspofungin† 5 μg > 11 – – < 10 <2 – – >2

Fluconazole‡ 25 μg > 19 15–18 < 14 – <8 16–32 > 64 –

Voriconazole 1 μg > 17 14–16 < 13 – <1 2 >4 –

*S
 usceptible (S), susceptible-dose dependent (S-DD), resistant (R), and nonsusceptible (NS) interpretive categories are
defined in Section 8.2 of CLSI document M44-A2.

†T
 he zone diameter interpretive standards in boldface were ‡ Isolates of Candida krusei are assumed to be intrinsically
adopted at a meeting of the subcommittee held on 26 resistant to fluconazole. The results of fluconazole
January 2008 in Tampa, Florida, USA. These zone diameter susceptibility testing of this species (zone diameter
interpretive standards are considered tentative for one year and MIC) should not be interpreted using this scale.
from publication of this document and are open for comment.

Table 2. Recommended Quality Control Zone Diameter (mm) Ranges2,8-10

Antifungal Disk C. albicans C. parapsilosis C. tropicalis C. krusei‡
Agent Content ATCC®* 90028 ATCC® 22019 ATCC® 750 ATCC® 6258

Caspofungin 5 μg 18–27 14–23 20–27 19–26

Fluconazole 25 μg 28–39 22–33 26–37 —†

Posaconazole 5 μg 24–34 25–36 23–33 23–31

Voriconazole 1 μg 31–42 28–37 —† 16–25

* ATCC is a registered trademark of the American Type Culture Collection.

† Quality control ranges have not been established for ‡A

 s Issatchenkia orientalis is now known to be the sexual
these strain/antimicrobial agent combinations, owing form (the teleomorph) of C. krusei, it would be technically
to their extensive interlaboratory variation during initial correct to use I. orientalis as the name for this fungus.
quality control studies. However, this change would confuse most users and the
far more widely used name C. krusei is retained.

For use with CLSI document M44-A2—Method for Antifungal Disk Diffusion Susceptibility Testing of Yeasts;
Approved Guideline—Second Edition (August 2009)

Infobase 2013 - Release Date:©2009 Clinical

April 2013. and Laboratory
This Document is protected by Standards Institute.
international copyright laws.All rights reserved. | www.clsi.org
 Glossary: Abbreviations/Routes of Administration/Drug Class
for Antifungal Agents
Antifungal Agent
Agent Abbreviation*,† Routes of Administration‡ Drug Class

PO IV

Caspofungin CAS – X Echinocandin

Fluconazole FLC X X Azole

Posaconazole POS X – Azole

Voriconazole VRC X X Azole

PO, per os (oral); IV, intravenous.

* Abbreviations assigned to one or more diagnostic products in the United States. If no diagnostic product is available,
abbreviation is that of the manufacturer.

† Alternative abbreviations: caspofungin (CFG); fluconazole (FLU, FLS, FCA, ‡ As available in the United States.
FLZ, FLC, FC, FZ); posaconazole (PCO, POC); voriconazole (VCO, VOC, VO).

References
1  faller MA, Diekema DJ, Ostrosky-Zeichner L, et al. Correlation of MIC with outcome for Candida species tested against caspofungin,
P
anidulafungin, and micafungin: analysis and proposal for interpretive MIC breakpoints. J Clin Microbiol. 2008;46(8):2620-2629.
2 Brown SD, Tracezewski MM. Caspofungin disk diffusion breakpoints and quality control. J Clin Microbiol. 2008;46(6):1927-1929.
3  ex JH, Pfaller MA, Galgiani JN, et al. Subcommittee on Antifungal Susceptibility Testing of the National Committee for Clinical Laboratory
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Standards. Development of interpretive breakpoints for antifungal susceptibility testing: Conceptual framework and analysis of in vitro-in
vivo correlation data for fluconazole, itraconazole, and Candida infections. Clin Infect Dis. 1997;24(2):235-247.
4 P
 faller MA, Diekema DJ, Sheehan DJ. Interpretive breakpoints for fluconazole and Candida revisited: a blueprint for the future of
antifungal susceptibility testing. Clin Microbiol Rev. 2006;19(2):435-447.
5  arry AL, Pfaller MA, Rennie RP, Fuchs PC, Brown SD. Precision and accuracy of fluconazole susceptibility testing by broth
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microdilution, Etest, and disk diffusion methods. Antimicrob Agents Chemother. 2002;46(6):1781-1784.
6  faller MA, Hazen KC, Messer SA, et al. Comparison of results of fluconazole disk diffusion testing for Candida species with results from
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a central reference laboratory in the ARTEMIS global antifungal surveillance program. J Clin Microbiol. 2004;42(8):3607-3612.
7 P
 faller MA, Diekema DJ, Rex JH, et al. Correlation of MIC with outcome for Candida species tested against voriconazole: analysis
and proposal for interpretive breakpoints. J Clin Microbiol. 2006;44(3):819-826.
8 B
 arry AL, Bille J, Brown SD, et al. Quality control limits for fluconazole disk susceptibility tests on Mueller-Hinton agar with
glucose and methylene blue. J Clin Microbiol. 2003;41(7):3410-3412.
9 B
 rown S, Traczewski M. Quality control limits for posaconazole disk susceptibility tests on Mueller-Hinton agar with glucose
and methylene blue. J Clin Microbiol. 2007;45(1):222-223.
10 P
 faller MA, Barry A, Bille J, et al. Quality control limits for voriconazole disk susceptibility test on Mueller-Hinton agar with
glucose and methylene blue. J Clin Microbiol. 2004;42(4):1716-1718.

For use with CLSI document M44-A2—Method for Antifungal Disk Diffusion Susceptibility Testing of Yeasts;
Approved Guideline—Second Edition (August 2009)

Infobase 2013 - Release Date:©2009 Clinical

April 2013. and Laboratory
This Document is protected by Standards Institute.
international copyright laws.All rights reserved. | www.clsi.org