Performance Standards for Antifungal Disk Diffusion

Susceptibility Testing of Nondermatophyte Filamentous

Fungi; Informational Supplement (M51-S1) (Approved)

Table 1. Tentative Zone Diameter Epidemiological Cutoff Values (ECV) and

Corresponding Minimal Inhibitory Concentration (MIC) or Minimal Effective
Concentration (MEC) for Filamentous Fungi1,a
Zone Diameter, Nearest Equivalent MIC or
Whole (mm) MECb ECV (μg/mL)
Antifungal Agent Disk Content (μg) ECV ECV

Amphotericin B 10 15 1

Caspofungin 5 17 1

Itraconazole 10 17 1

Posaconazole 5 17 1

Voriconazole 1 17 1

aE
 CV: The value shown is the highest MIC/MEC (lowest zone diameter) of isolates belonging to the wild type (WT) distribution.
The ECV is expressed as WT < X μg/mL (WT > X mm).
bM
 EC applies to caspofungin only; preliminary ECV MIC values for three triazoles and Aspergillus fumigatus have been recently
established2 and work is underway for some other Aspergillus spp. and antifungal agents.

NOTE 1: These tentative criteria have not been approved
for use in clinical testing but were proposed on an
epidemiological basis during evaluation of a series of
putative susceptible and resistant isolates.1 As discussed
in Section 8 of M51-A, the clinical relevance of testing this
group of fungal pathogens remains uncertain, and either
MIC or zone diameter breakpoints with proven clinical
relevance have not yet been identified or approved by CLSI
or any regulatory agency.
NOTE 2: It is recommended that ECV values should be
established by species. However, because 18 species were
included in the collaborative study1 and some species were
represented by a small number of isolates, the values
seen in Table 1 were established for all species together.
As stated in footnote b, ECV MIC data have already been
published by CLSI methodologies for only Aspergillus
fumigatus and three triazoles.2 As data for other species/
agent combinations are developed, Table 1 will be revised
as necessary in the subsequent versions of M51-S1.

For use with CLSI document M51-A—Method for Antifungal Disk Diffusion Susceptibility Testing
of Nondermatophyte Filamentous Fungi; Approved Guideline (May 2010)

Infobase 2013 - Release Date: April 2013. This Document is protected by international copyright laws.
©2010 Clinical and Laboratory Standards Institute. All rights reserved. | www.clsi.org
Table 2. Recommended Reference Control Zone Diameter (mm) Ranges
P. variotii ATCC®*
Antifungal Agent Disk Content (μg) MYA 3630† C. krusei ATCC®* 6258†,‡

Amphotericin B 10 13–22 (9–19) 19–27 (12–25)

Caspofungin 5 23–29 (23–30) 14–24 (18–27)

Itraconazole 10 25–31 (23–31) 21–30 (20–29)

Posaconazole 5 35–46 (37–45) 31–43 (30–41)

Voriconazole 1 40–53 (41–53) 29–38 (25–35)

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

† Reference control ranges obtained at 24 (and 48) hours in the collaborative study.1

‡B
 ecause Issatchenkia orientalis is now known to be the sexual form (the teleomorph) of C. krusei, it would be technically correct to use I. orientalis
as the name for this fungus. However, this change would confuse most users and the far more widely used name C. krusei is retained.

References
1 
Espinel-Ingroff A, Arthington-Skaggs B, Iqbal N, et al. Multicenter evaluation of a new disk agar diffusion method for susceptibility testing
of filamentous fungi with voriconazole, posaconazole, itraconazole, amphotericin B and caspofungin. J Clin Microbiol. 2007;45:1811-1820.
2  faller MA, Diekema DJ, Ghannoum MA, et al. Wild-type MIC distribution and epidemiological cutoff values for Aspergillus fumigatus and three
P
triazoles as determined by the Clinical and Laboratory Standards Institute broth microdilution methods. J Clin Microbiol. 2009;47:3142-3146.

Glossary. Abbreviations/Routes of Administration/Drug Class for Antifungal Agents

Antifungal Agent
Agent Abbreviationa,b Routes of Administrationc Drug Class

PO* IV†

Amphotericin B AMB X Polyene

Caspofungin CAS X Echinocandin

Itraconazole ITC X X Azole

Posaconazole POS X Azole

Voriconazole VRC X X Azole

* PO = per OS (oral)
† IV = intravenous

a Abbreviations assigned to one or more diagnostic products in the United States. If no diagnostic product is available,
abbreviation is that of the manufacturer.
b Alternative abbreviations: amphotericin B (AMT); caspofungin (CFG); itraconazole (ITR, ICO); posaconazole (PCO, POC);
voriconazole (VOR, VCO, VOC).
c As available in the United States.

For use with CLSI document M51-A—Method for Antifungal Disk Diffusion Susceptibility Testing
of Nondermatophyte Filamentous Fungi; Approved Guideline (May 2010)

Infobase 2013 - Release Date: April 2013. This Document is protected by international copyright laws.
©2010 Clinical and Laboratory Standards Institute. All rights reserved. | www.clsi.org