CLSI M23-A5 (Tier 2) Broth Microdilution

Quality Control Study for Manogepix

(formerly APX001A)

Michael D. Huband, Associate Director

Shawn A. Messer, Microbiologist III
Kelley A. Fedler, Microbiologist-QC Specialist
Amy A. Watters, Lead Automation Scientist
Mariana Castanheira, CSO

JMI Laboratories
North Liberty, Iowa
USA
Manogepix broth microdilution QC summary

• This quality control study follows the current CLSI M23 (2018) document

• Eight laboratories participated

• Three lots of Roswell Park Memorial Institute (RPMI) 1640 medium supplemented with L-glutamine
(0.3 g/L), without bicarbonate, and with phenol red indicator (0.0005 g/L) obtained from 3 different
manufacturers
• Medium A – FUJIFILM Irvine Scientific (Santa Ana, CA, USA) lot #9513160101A – M19023A
• Medium B – Sigma-Aldrich (St. Louis, MO, USA), lot #SLBQ8757V – M19023B
• Medium C – Hyclone Laboratories (Logan UT, USA), lot #AC10257966A – M19023C

• Compounds tested: Manogepix, Voriconazole, and Micafungin

Calculated broth microdilution MIC/MEC quality
control ranges for manogepix
Calculated Manogepix Calculated Manogepix Previously Approved
QC / Reference strain
24 hour QC range (µg/mL) 48 hour QC range (µg/mL) Manogepix QC range
(# of dilutions; % in range) (# of dilutions; % in range) (µg/mL)
Candida albicans 0.004 – 0.015a 0.004 – 0.015a --
ATCC 90028 (3; 100.0%) (3; 100.0%)
Candida parapsilosis 0.008 – 0.03a 0.008 – 0.03a 0.015 – 0.12
ATCC 22019 (3; 100.0%) (3; 94.3%)b (24 hour MIC)
Aspergillus flavus 0.004 – 0.03c 0.008 – 0.06c 0.008 – 0.06
ATCC 204304 (4; 99.2%) (4; 99.6%) (48 hour MEC)
Aspergillus fumigatus 0.008 – 0.03c 0.008 – 0.06d 0.015 – 0.06
ATCC MYA-3626 (3; 92.5%)b (4; 98.6%) (48 hour MEC)
a CLSI and RangeFinder calculations.
b Values listed in red are less than the 95.0% minimum required to establish a QC range.
c CLSI calculation.
d RangeFinder calculation.
Table 1 Inter- and intra-laboratory comparisons of manogepix 24-hour MIC values for
Candida albicans ATCC 90028 in an 8-laboratory protocol meeting the study
design guidelines found in CLSI M23 (2018)

Occurrences by media lot

MIC Laboratory code (occurrences): Total
(µg/mL) A B C A B C D E Fa G H
0.001 29
CLSI range:
0.002 1
0.004 – 0.015 µg/mL
0.004 14 13 13 3 10 27 40
(100.0% 210/210)
0.008 45 47 47 29 27 30 30 20 3 139
0.015 11 10 10 1 30 31
0.03
RangeFinder range:
Total 70 70 70 30 30 30 30 30 30 30 30 210 0.004 – 0.015 µg/mL
(100.0%; 210/210)
Mean 0.008 0.008 0.008 0.008 0.015 0.008 0.008 0.008 0.001 0.007 0.004 0.008
Median 0.008 0.008 0.008 0.008 0.015 0.008 0.008 0.008 0.001 0.008 0.004 0.008
Mode 0.008 0.008 0.008 0.008 0.015 0.008 0.008 0.008 0.001 0.008 0.004 0.008

Geometric
0.007 0.007 0.008 0.008 0.015 0.007 0.008 0.008 0.001 0.006 0.004 0.008
mean

Range (mm) 3 3 3 2 1 2 1 1 2 2 2 3
a Laboratory F was a statistical outliers for the modal manogepix MIC values and was excluded from the analysis.
Figure 1 Manogepix 24-hour MIC distributions by
medium lot for Candida albicans ATCC 90028

Proposed QC range
0.004 – 0.015 µg/mL CLSI range:
(100%; 210/210) 0.004 – 0.015 µg/mL
(100.0% 210/210)

RangeFinder range:
0.004 – 0.015 µg/mL
(100.0%; 210/210)
Table 2 Inter- and intra-laboratory comparisons of manogepix 48-hour MIC values for
Candida albicans ATCC 90028 in an 8-laboratory protocol meeting the study
design guidelines found in CLSI M23 (2018)

Occurrences by media lot

MIC Laboratory code (occurrences): Total
(µg/mL) A B C A B C D E Fa G H
0.001 5
CLSI range:
0.002 19
0.004 – 0.015 µg/mL
0.004 1 1 1 6 3 3
(100.0% 210/210)
0.008 57 59 59 29 30 29 30 30 27 175
0.015 12 10 10 1 30 1 32
0.03
RangeFinder range:
Total 70 70 70 30 30 30 30 30 30 30 30 210 0.004 – 0.015 µg/mL
(100.0%; 210/210)
Mean 0.009 0.009 0.009 0.008 0.015 0.008 0.008 0.008 0.002 0.008 0.008 0.009
Median 0.008 0.008 0.008 0.008 0.015 0.008 0.008 0.008 0.002 0.008 0.008 0.008
Mode 0.008 0.008 0.008 0.008 0.015 0.008 0.008 0.008 0.002 0.008 0.008 0.008

Geometric
0.009 0.009 0.009 0.008 0.015 0.008 0.008 0.008 0.002 0.008 0.007 0.009
mean

Range (mm) 3 3 3 2 1 1 2 1 3 1 2 3
a Laboratory F was a statistical outliers for the mean, median, and modal manogepix MIC values and was excluded from the analysis.
Figure 2 Manogepix 48-hour MIC distributions by
medium lot for Candida albicans ATCC 90028
Proposed QC range
0.004 – 0.015 µg/mL
(100%; 210/210)
CLSI range:
0.004 – 0.015 µg/mL
(100.0% 210/210)

RangeFinder range:
0.004 – 0.015 µg/mL
(100.0%; 210/210)
Table 3 Inter- and intra-laboratory comparisons of 24-hour manogepix MIC values for
Candida parapsilosis ATCC 22019 in an 8-laboratory protocol meeting the study
design guidelines found in CLSI M23 (2018)

Occurrences by media
MIC lot Laboratory code (occurrences): Total
A B C A B C D E F G Ha CLSI range:
(µg/mL)
0.008 – 0.03 µg/mL
0.004 30
(100.0% 210/210)
0.008 3 3 4 3 3 4 10
0.015 62 62 61 30 16 26 30 30 27 26 185
0.03 5 5 5 14 1 15 RangeFinder range:
0.06
0.008 – 0.03 µg/mL
(100.0%; 210/210)
0.12
Total 70 70 70 30 30 30 30 30 30 30 30 210

Current CLSI QC range:

Mean 0.016 0.016 0.016 0.015 0.022 0.015 0.015 0.015 0.014 0.014 0.004 0.016
0.015 – 0.12 µg/mL
Median 0.015 0.015 0.015 0.015 0.015 0.015 0.015 0.015 0.015 0.015 0.004 0.015
Mode 0.015 0.015 0.015 0.015 0.015 0.015 0.015 0.015 0.015 0.015 0.004 0.015
Proposed new
Geometric mean 0.015 0.015 0.015 0.015 0.021 0.014 0.015 0.015 0.014 0.014 0.004 0.015 CLSI QC range:
0.008 – 0.03 µg/mL
Range (mm) 3 3 3 1 2 3 1 1 2 2 1 3 (100.0% 210/210)
a Laboratory H was a statistical outliers for the mean, median, and modal manogepix MIC values and was excluded from the analysis.
Figure 3 Manogepix 24-hour MIC distributions by
medium lot for Candida parapsilosis ATCC 22019

Proposed QC range
CLSI range:
0.008 – 0.03 µg/mL
0.008 – 0.03 µg/mL
(100%; 210/210)
(100.0% 210/210)

RangeFinder range:
0.008 – 0.03 µg/mL
(100.0%; 210/210)

Current CLSI QC range:

0.015 – 0.12 µg/mL

Proposed new
CLSI QC range:
0.008 – 0.03 µg/mL
(100.0% 210/210)
Table 4 Inter- and intra-laboratory comparisons of 48-hour manogepix MIC values for
Candida parapsilosis ATCC 22019 in an 8-laboratory protocol meeting the study
design guidelines found in CLSI M23 (2018)

Occurrences by media
MIC lot Laboratory code (occurrences): Total
(µg/mL) A B C A Ba C D E F G Hb
CLSI range:
0.004 30 0.008 – 0.03 µg/mL
0.008 (94.3% 198/210)
0.015 60 59 59 30 28 30 30 30 30 178
0.03 6 7 7 18 2 20
0.06 4 4 4 12 12
RangeFinder range:
Total 70 70 70 0.008 – 0.03 µg/mL
(94.3%; 198/210)
Mean 0.019 0.019 0.019 0.015 0.04 0.016 0.015 0.015 0.015 0.015 0.004 0.019
Median 0.015 0.015 0.015 0.015 0.03 0.015 0.015 0.015 0.015 0.015 0.004 0.015
Mode 0.015 0.015 0.015 0.015 0.03 0.015 0.015 0.015 0.015 0.015 0.004 0.015

Geometric mean 0.017 0.017 0.017 0.015 0.04 0.016 0.015 0.015 0.015 0.015 0.004 0.017

Range (mm) 3 3 2 1 2 2 1 1 1 1 1 3
a Laboratory B was a statistical outlier for the mean manogepix MIC value.
b Laboratory H was a statistical outlier for the mean, median, and modal manogepix MIC values and was excluded from the analysis.
c Values listed in red are less than the 95.0% minimum required to establish a QC range.
Figure 4 Manogepix 48-hour MIC distributions by
medium lot for Candida parapsilosis ATCC 22019

No Proposed QC range

CLSI range:
0.008 – 0.03 µg/mL
(94.3% 198/210)

RangeFinder range:
0.008 – 0.03 µg/mL
(94.3%; 198/210)
Table 5 Inter- and intra-laboratory comparisons of 24-hour manogepix MEC values for
Aspergillus flavus ATCC 204304 in an 8-laboratory protocol meeting the study
design guidelines found in CLSI M23 (2018)

Occurrences by media
MEC lot Laboratory code (occurrences): Total
(µg/mL) A B C Aa B C D E F G Ha

0.002
0.004 1 1 2 2
CLSI range:
0.008 39 37 34 1 19 9 30 21 27 3 110 0.004 – 0.03 µg/mL
0.015 20 22 21 9 15 9 18 9 3 63 (99.2% 238/240)
0.03 21 20 22 18 15 3 27 63
0.06 2 2 2

Total 80 80 80 30 30 30 30 30 30 30 30 240 RangeFinder range:

0.004 – 0.06 µg/mL
Mean 0.016 0.015 0.017 0.03 0.02 0.01 0.014 0.008 0.01 0.009 0.03 0.016 (100.0%; 240/240)
Median 0.015 0.015 0.015 0.03 0.02 0.008 0.015 0.008 0.008 0.008 0.03 0.015 5 dilutions
Mode 0.008 0.008 0.008 0.03 0.015, 0.03 0.008 0.015 0.008 0.008 0.008 0.03 0.008

Geometric mean 0.013 0.013 0.014 0.02 0.02 0.01 0.013 0.008 0.01 0.009 0.03 0.014

Range (mm) 3 4 5 4 2 3 3 1 2 2 3 5
a Laboratories A and H were statistical outliers for the modal manogepix MEC values.
Figure 5 Manogepix 24-hour MEC distributions by
medium lot for Aspergillus flavus ATCC 204304

Proposed QC range
0.004 – 0.03 µg/mL
(99.2%; 238/240)
CLSI range:
0.004 – 0.03 µg/mL
(99.2% 238/240)

RangeFinder range:
0.004 – 0.06 µg/mL
(100.0%; 240/240)
5 dilutions
Table 6 Inter- and intra-laboratory comparisons of 48-hour manogepix MEC values for
Aspergillus flavus ATCC 204304 in an 8-laboratory protocol meeting the study
design guidelines found in CLSI M23 (2018)

Occurrences by media lot

MEC Laboratory code (occurrences): Total
(µg/mL) A B C Aa Ba C Da E F G Ha CLSI range:
0.008 – 0.06 µg/mL
0.004
(99.6% 239/240)
0.008 29 30 25 14 30 13 27 84
0.015 13 15 17 9 16 3 14 3 45
0.03 32 26 25 11 15 24 3 30 83
RangeFinder range:
0.06 6 9 12 18 6 3 27
0.004 – 0.06 µg/mL
0.12 1 1 1
(99.6%; 239/240)
Total 80 80 80 30 30 30 30 30 30 30 30 240
5 dilutions

Mean 0.02 0.02 0.03 0.05 0.03 0.01 0.03 0.008 0.013 0.009 0.03 0.02
Median 0.015 0.015 0.015 0.06 0.03 0.015 0.03 0.008 0.015 0.008 0.03 0.015
Mode 0.03 0.008 0.008, 0.03 0.06 0.03 0.015 0.03 0.008 0.015 0.008 0.03 0.008
Current CLSI QC range:
0.008 – 0.06 µg/mL
Geometric mean 0.02 0.02 0.02 0.05 0.03 0.01 0.03 0.008 0.012 0.009 0.03 0.02

Range (mm) 4 4 5 3 3 2 3 1 3 2 1 5
a Laboratories A, B, D, and H were statistical outliers for the modal manogepix MEC values.
Figure 6 Manogepix 48-hour MEC distributions by
medium lot for Aspergillus flavus ATCC 204304

Current CLSI QC range CLSI range:

0.008 – 0.06 µg/mL 0.008 – 0.06 µg/mL
(99.6% 239/240)

RangeFinder range:
0.004 – 0.06 µg/mL
(99.6%; 239/240)
5 dilutions

Current CLSI QC range:

0.008 – 0.06 µg/mL
Table 7 Inter- and intra-laboratory comparisons of 24-hour manogepix MEC values for
Aspergillus fumigatus ATCC MYA-3626 in an 8-laboratory protocol meeting the study
design guidelines found in CLSI M23 (2018)

Occurrences by media
MEC lot Total
Laboratory code (occurrences):
(µg/mL)
A B C A B C D E Fa G H
0.002
0.004 5 5 5 15 15 CLSI range:
0.008 8 8 8 8 15 1 24
0.008 – 0.03 µg/mL
0.015 48 50 47 23 21 22 20 30 29 145
0.03 17 16 20 6 8 10 29 53
(92.5%; 222/240)
0.06 2 1 1 1 1 3

Total 80 80 80 30 30 30 30 30 30 30 30 240
RangeFinder range:
0.004 – 0.06 µg/mL
Mean 0.018 0.017 0.017 0.02 0.021 0.013 0.02 0.015 0.006 0.015 0.03 0.017
(100.0%; 240/240)
Median 0.015 0.015 0.015 0.015 0.015 0.015 0.015 0.015 0.006 0.015 0.03 0.015 5 dilutions

Mode 0.015 0.015 0.015 0.015 0.015 0.015 0.015 0.015 0.004, 0.008 0.015 0.03 0.015

Geometric mean 0.016 0.015 0.015 0.018 0.019 0.013 0.019 0.015 0.006 0.015 0.03 0.015

Range (mm) 5 5 4 3 3 2 2 1 2 1 2 5
a Laboratory F was a statistical outlier for the mean manogepix MEC value.
Figure 7 Manogepix 24-hour MEC distributions by
medium lot for Aspergillus fumigatus ATCC MYA-3626
No Proposed QC range

CLSI range:
0.008 – 0.03 µg/mL
(92.5%; 222/240)

RangeFinder range:
0.004 – 0.06 µg/mL
(100.0%; 240/240)
5 dilutions
Table 8 Inter- and intra-laboratory comparisons of 48-hour manogepix MEC values for
Aspergillus fumigatus ATCC MYA-3626 in an 8-laboratory protocol meeting the study
design guidelines found in CLSI M23 (2018)

Occurrences by media lot

MIC Laboratory code (occurrences): Total
(µg/mL) A B C A B C D E Fa G H

0.004
0.008 1 1 27 1
Current CLSI QC range:
0.015 22 22 23 9 28 3 30 67b 0.015 – 0.06 µg/mL
0.03 40 37 39 19 15 1 21 30 30 116 (98.1%; 206/210)
0.06 7 9 7 2 12 9 23
0.12 1 1 1 3 3
0.25
RangeFinder rangeb:
Total 70 70 70 30 30 30 30 30 30 30 30 210 0.008 – 0.06 µg/mL
(98.6%; 207/210)
Mean 0.03 0.03 0.03 0.03 0.05 0.016 0.04 0.03 0.009 0.015 0.03 0.03
Median 0.03 0.03 0.03 0.03 0.05 0.015 0.03 0.03 0.008 0.015 0.03 0.03
Mode 0.03 0.03 0.03 0.03 0.03 0.015 0.03 0.03 0.008 0.015 0.03 0.03

Geometric mean 0.03 0.02 0.03 0.03 0.05 0.015 0.04 0.03 0.009 0.015 0.03 0.03

Range (mm) 3 4 3 3 3 3 2 1 2 1 1 5
a Laboratory F was a statistical outlier for the mean and modal manogepix MEC values and was excluded from the analysis.
b 57.8% MEC shoulder at 0.015 µg/mL suggests expanding to a 4-dilution QC range.
Figure 8 Manogepix 48-hour MEC distributions by
medium lot for Aspergillus fumigatus ATCC MYA-3626

Current CLSI QC range

0.015 – 0.06 µg/mL
Current CLSI QC range:
0.015 – 0.06 µg/mL
(98.1%; 206/210)

57.8% MIC shoulder

at 0.015 µg/mL RangeFinder range:
0.008 – 0.06 µg/mL
(98.6%; 207/210)
Proposed broth microdilution MIC/MEC quality
control ranges for manogepix
Proposed Manogepix Proposed Manogepix Previously Approved
QC / Reference strain
24-hour QC range (µg/mL) 48-hour QC range (µg/mL) Manogepix QC range
(# of dilutions; % in range) (# of dilutions; % in range) (µg/mL)
Candida albicans 0.004 – 0.015a 0.004 – 0.015a
--
ATCC 90028 (3; 100.0%) (3; 100.0%)
0.008 – 0.03a
Candida parapsilosis 0.008 – 0.03a 0.015 – 0.12
(3; 94.3%)
ATCC 22019 (3; 100.0%) (24-hour MIC)
No proposed QC range
0.008 – 0.06b
Aspergillus flavus 0.004 – 0.03b 0.008 – 0.06
(4; 99.6%)
ATCC 204304 (4; 99.2%) (48-hour MEC)
Same as current range
0.008 – 0.03b
Aspergillus fumigatus 0.008 – 0.06c 0.015 – 0.06
(3; 92.5%)
ATCC MYA-3626 (4; 98.6%) (48-hour MEC)
No proposed QC range

a CLSI and RangeFinder calculations.

b CLSI calculation.
c RangeFinder calculation.
Acknowledgements
Investigator Institution
R. Flamm, PhD JMI Laboratories, North Liberty, IA, USA

D. Hardy, PhD University of Rochester Medical Center, Rochester, NY, USA

C. Pillar, PhD Micromyx, LLC, Kalamazoo, MI, USA

D. Diekema, MD University of Iowa Hospitals and Clinics, Iowa City, IA, USA

L. Ostrosky-Zeichner McGovern Medical School, Houston, TX, USA

N. Wiederhold, PharmD University of Texas Health Science Center, San Antonio, TX, USA

S. Lockhart, PhD Centers for Disease Control and Prevention, Atlanta, GA, USA

M. Ghannoum, MD Case Western Reserve University, Cleveland, OH, USA

Thank you!
JMILabs.com
 Backup Slides

• Backup Slides – Voriconazole and Micafungin QC

Results
Table 9 Inter- and intra-laboratory comparisons of 24-hour micafungin MIC values for
Candida parapsilosis ATCC 22019 in an 8-laboratory protocol meeting the study
design guidelines found in CLSI M23 (2018)

Occurrences by
MIC media lot Laboratory code (occurrences): Total
(µg/mL) A B C A B C D Ea F G H
0.25
0.5 16 12 - 3 20 3 2 28
1 64 68 - 20 20 17 20 17 18 20 132
2 Current CLSI QC range (M60; 2017)
4
MIC range # of
% in range
(µg/mL) dilutions
Total 80 80 - 20 20 20 20 20 20 20 20 160
100.0%
0.5– 2 3
(160/160)
Mean 0.9 0.9 - 1 1 0.9 1 0.5 0.9 1 1 0.9
Median 1 1 - 1 1 1 1 0.5 1 1 1 1
Mode 1 1 - 1 1 1 1 0.5 1 1 1 1

Geometric
0.9 0.9 - 1 1 0.9 1 0.5 0.9 0.9 1 0.9
mean

Range (mm) 2 2 - 1 1 2 1 1 2 2 1 2
a Laboratory E was a statistical outlier for the mean micafungin MIC value.
Table 10 Inter- and intra-laboratory comparisons of 24-hour voriconazole MIC values
for Candida parapsilosis ATCC 22019 in an 8-laboratory protocol meeting the study
design guidelines found in CLSI M23 (2018)

Occurrences by media lot

MIC Total
Laboratory code (occurrences):
(µg/mL) A B C A B Ca D Ea F G H
0.008
0.015 32 33 33 21 3 30 3 11 30 98
0.03 33 30 32 9 27 13 27 19 95
0.06 15 17 15 17 30 47 Current CLSI QC range (M60; 2017)
0.12 MIC range # of
% in range
0.25 (µg/mL) dilutions
100.0%
0.015– 0.12 4
Total 80 80 80 30 30 30 30 30 30 30 30 240 (240/240)

Mean 0.03 0.03 0.03 0.02 0.03 0.05 0.015 0.06 0.03 0.03 0.015 0.03
Median 0.03 0.03 0.03 0.015 0.03 0.06 0.015 0.06 0.03 0.03 0.015 0.03
Mode 0.03 0.015 0.015 0.015 0.03 0.06 0.015 0.06 0.03 0.03 0.015 0.015

Geometric
0.03 0.03 0.03 0.02 0.03 0.04 0.015 0.06 0.03 0.02 0.015 0.03
mean

Range (mm) 3 3 3 2 2 2 1 1 2 2 1 3
a Laboratories C and E were statistical outliers for the modal voriconazole MIC values.
Table 11 Inter- and intra-laboratory comparisons of 48-hour voriconazole MIC values
for Candida parapsilosis ATCC 22019 in an 8-laboratory protocol meeting the study
design guidelines found in CLSI M23 (2018)

Occurrences by media lot

MIC Laboratory code (occurrences): Total
(µg/mL) A B C A B C D Ea F G H

0.015
0.03 45 46 46 30 3 23 24 27 30 137
0.06 25 24 23 27 29 7 6 3 72
0.12 10 10 11 1 30 31 Current CLSI QC range (M61; 2017)
0.25 MIC range # of
0.5 % in range
(µg/mL) dilutions
100.0%
Total 80 80 80 30 30 30 30 30 30 30 30 240 0.03 – 0.25 4
(240/240)
Mean 0.05 0.05 0.05 0.03 0.06 0.06 0.04 0.12 0.04 0.03 0.03 0.05
Median 0.03 0.03 0.03 0.03 0.06 0.06 0.03 0.12 0.03 0.03 0.03 0.03
Mode 0.03 0.03 0.03 0.03 0.06 0.06 0.03 0.12 0.03 0.03 0.03 0.03

Geometric mean 0.04 0.04 0.04 0.03 0.06 0.06 0.04 0.12 0.03 0.03 0.03 0.04

Range (mm) 3 3 3 1 2 2 2 1 2 2 1 3
a Laboratory E was a statistical outlier for the mean and modal voriconazole MIC values and is excluded from the analysis.
Table 12 Inter- and intra-laboratory comparisons of 48-hour voriconazole MIC values
for Aspergillus flavus ATCC 204304 in an 8-laboratory protocol meeting the study
design guidelines found in CLSI M23 (2018)

Occurrences by media lot

MIC Laboratory code (occurrences): Total
(µg/mL) A B C A B C D E F G H

0.12
0.25 15 15 15 9 30 6 45
0.5 37 28 34 15 21 4 26 15 18 99 Current CLSI QC range (M61; 2017)
1 23 36 28 15 24 4 9 12 23 87
2 5 1 3 2 7 9 MIC range # of
% in range
4 dilutions
(µg/mL)
8
81.3%
0.5 – 4 4
Total 80 80 80 30 30 30 30 30 30 30 30 240
(195/240)

Mean 0.7 0.7 0.7 0.8 0.4 1 0.6 0.25 0.6 0.7 1.2 0.7
Median 0.5 0.5 0.5 0.8 0.5 1 0.5 0.25 0.5 0.5 1 0.5
Mode 0.5 1 0.5 0.5, 1 0.5 1 0.5 0.25 0.5 0.5 1 0.5

Geometric mean 0.6 0.6 0.6 0.7 0.4 0.95 0.6 0.25 0.5 0.7 1.2 0.6

Range (mm) 4 4 4 2 2 3 2 1 3 2 2 4
Table 12 Inter- and intra-laboratory comparisons of 48-hour voriconazole MIC values
for Aspergillus fumigatus ATCC MYA-3626 in an 8-laboratory protocol meeting the
study design guidelines found in CLSI M23 (2018)

Occurrences by media lot

MIC Laboratory code (occurrences): Total
(µg/mL) A B C A B C D E F G H

0.12
0.25 17 21 21 30 6 23 59
0.5 55 51 51 30 30 15 27 18 7 30 157 Current CLSI QC range (M61; 2017)
1 8 8 8 15 3 6 24 MIC range # of
2 % in range
(µg/mL) dilutions

Total 80 80 80 30 30 30 30 30 30 30 30 240 100.0%

0.25 – 1 3
(240/240)
Mean 0.5 0.5 0.5 0.5 0.5 0.8 0.6 0.25 0.6 0.3 0.5 0.5
Median 0.5 0.5 0.5 0.5 0.5 0.8 0.5 0.25 0.5 0.25 0.5 0.5
Mode 0.5 0.5 0.5 0.5 0.5 0.5, 1 0.5 0.25 0.5 0.25 0.5 0.5

Geometric mean 0.5 0.4 0.5 0.5 0.5 0.7 0.5 0.25 0.5 0.3 0.5 0.5

Range (mm) 3 3 3 1 1 2 2 1 3 2 1 3