Graphical presentation of species

and agents where EUCAST has

introduced an Area of Technical
Uncertainty (ATU)

Version 1.0
February 2020
 Area of Technical Uncertainty
• The ATU is not a susceptibility testing category and does
not interfere with the interpretation of results into S, I and R.
• The ATU is a warning to laboratory staff to question the
susceptibility result and the categorisation.
• The ATUs are listed in the EUCAST Breakpoint Tables and
are defined by an MIC value and/or a range of inhibition
zone diameters.
• There is no mandatory action to an ATU.
– The warning may be ignored or acted upon.
• For more information, see the EUCAST guidance
document on technical uncertainty:
http://www.eucast.org/newsiandr/
 Alternative ways to handle a result
in the ATU
• Repeat the test
– only if a technical error is suspected
• Perform an alternative test
– perform an MIC or a genotypic test
• Downgrade the susceptibility category
– from S→I, I→R or S→R
• Include the uncertainty as part of the report
– categorise according to the breakpoints and add a comment on
uncertainty
• Omit an uncertain result
– report blank with a comment on uncertainty
• Discuss the results with the clinical colleague
Explanation of graphs:
• These graphs present inhibition zone diameter distributions with MIC values or
resistance mechanisms as coloured bars. A larger than normal number of isolates with
MIC values close to the edge of the wild-type distribution and/or close to EUCAST
clinical breakpoints were intentionally included.

• This presentation is based on EUCAST Clinical Breakpoint Tables v. 10.0.

Area of Technical
Zone diameter Uncertainty
breakpoint

Resistant (R)

Susceptible, Increased exposure (I)

Susceptible, standard dosing regimen (S)

 Current ATUs
Enterobacterales Staphylococcus spp.
Amoxicillin clavulanic acid (systemic) Cefoxitin (S. epidermidis)
Piperacillin-tazobactam Ceftaroline (S. aureus, pneumonia and
Ceftaroline non-pneumonia)
Ciprofloxacin Ceftobiprole (S. aureus)
Amikacin (S. aureus)

Pseudomonas spp. Haemophilus influenzae

Piperacillin
Piperacillin-tazobactam
Ceftazidime-avibactam (P. aeruginosa)
Colistin (MIC only)
Piperacillin-tazobactam (PBP3 mutations)
Cefepime (PBP3 mutations)
Cefotaxime (PBP3 mutations)
Cefpodoxime (PBP3 mutations)
Ceftriaxone (PBP3 mutations)
Cefuroxime (iv and oral, PBP3 mutations)
Imipenem (PBP3 mutations)
Enterobacterales
 Amoxicillin-clavulanic acid 20-10 µg vs MIC
Enterobacterales, 325 isolates
70
ATU

60 MIC
(mg/L)
50 ≥128
No of observations

64
40 32
16
30 8
4
20 2
1
10 0.5

0
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints (systemic infections) ATU

MIC S≤8, R>8 mg/L
Zone diameter S≥19, R<19 mm 19-20 mm
 Amoxicillin-clavulanic acid 20-10 µg vs MIC
E. coli, 149 isolates
18
ATU
16
MIC
14 (mg/L)
No of observations

12 ≥128
64
10 32
8 16
8
6 4
2
4
1
2

0
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints (systemic infections) ATU

MIC S≤8, R>8 mg/L
Zone diameter S≥19, R<19 mm 19-20 mm
 Amoxicillin-clavulanic acid 20-10 µg vs MIC
K. pneumoniae, 86 isolates
30
ATU

25 MIC
(mg/L)
No of observations

20 ≥128
64
32
15
16
8
10 4
2
5 1

0
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints (systemic infections) ATU

MIC S≤8, R>8 mg/L
Zone diameter S≥19, R<19 mm 19-20 mm
 Amoxicillin-clavulanic acid 20-10 µg vs MIC
P. mirabilis, 58 isolates
18
ATU
16
MIC
14 (mg/L)
≥128
No of observations

12
64
10 32
16
8 8
4
6
2
4 1
0.5
2

0
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints (systemic infections) ATU

MIC S≤8, R>8 mg/L
Zone diameter S≥19, R<19 mm 19-20 mm
 Piperacillin-tazobactam 30-6 μg vs. MIC
Enterobacterales, 531 isolates (840 correlates)
100
ATU
90

80 MIC
(mg/L)
70
No of observations

≥128
60 64
32
50
16
40 8

30 4
2
20 ≤1
10

0
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤8, R>16 mg/L 16 mg/L
Zone diameter S≥20, R<17 mm 17-19 mm
 Piperacillin-tazobactam 30-6 μg vs. MIC
E. coli, 294 isolates (496 correlates)
50
ATU
45

40 MIC
(mg/L)
35
No of observations

≥128
30 64
32
25
16
20 8

15 4
2
10 ≤1
5

0
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤8, R>16 mg/L 16 mg/L
Zone diameter S≥20, R<17 mm 17-19 mm
 Piperacillin-tazobactam 30-6 μg vs. MIC
K. pneumoniae, 123 isolates (185 correlates)
35
ATU

30
MIC
(mg/L)
25
No of observations

≥128
64
20
32
16
15
8
4
10
2
≤1
5

0
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤8, R>16 mg/L 16 mg/L
Zone diameter S≥20, R<17 mm 17-19 mm
 Ceftaroline 5 μg vs. MIC
Enterobacterales, 249 isolates (980 correlates) MIC
100 (mg/L)
ATU
≥128
90
64
80 32
70 16
No of observations

8
60
4
50 2
1
40
0.5
30 0.25
20 0.125
0.06
10
0.03
0 0.016
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

0.008
Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤0.5, R>0.5 mg/L
Zone diameter S≥23, R<23 mm 22-23 mm
 Ceftaroline 5 μg vs. MIC
E. coli, 110 isolates (519 correlates) MIC
60 (mg/L)
ATU
≥128

50 64
32
16
No of observations

40
8
4
30 2
1
0.5
20
0.25
0.125
10 0.06
0.03
0 0.016
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

0.008
Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤0.5, R>0.5 mg/L
Zone diameter S≥23, R<23 mm 22-23 mm
 Ceftaroline 5 μg vs. MIC
K. pneumoniae, 61 isolates (175 correlates)
20 MIC
ATU
(mg/L)
18
≥128
16 64
14 32
No of observations

16
12
8
10 4
2
8
1
6 0.5
4 0.25
0.125
2
0.06
0 0.03
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤0.5, R>0.5 mg/L
Zone diameter S≥23, R<23 mm 22-23 mm
 Ciprofloxacin 5 μg vs. MIC
Enterobacterales, 471 isolates (490 correlates)
70
ATU

60 MIC
(mg/L)
50 ≥8
No of observations

4
40 2
1
30 0.5
0.25
20 0.125
0.06
10 ≤0.03

0
10
12
14
16
18
20
22
24
26
28
30
32
34
36
38
40
42
44
46
48
50
6
8

Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤0.25, R>0.5 mg/L 0.5 mg/L
Zone diameter S≥25, R<22 mm 22-24 mm
 Ciprofloxacin 5 μg vs. MIC
E. coli, 376 isolates (390 correlates)
60
ATU

50 MIC
(mg/L)
≥8
No of observations

40
4
2
30 1
0.5
0.25
20
0.125
0.06
10 ≤0.03

0
10
12
14
16
18
20
22
24
26
28
30
32
34
36
38
40
42
44
46
48
50
6
8

Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤0.25, R>0.5 mg/L 0.5 mg/L
Zone diameter S≥25, R<22 mm 22-24 mm
 Ciprofloxacin 5 μg vs. MIC
K. pneumoniae, 75 isolates (82 correlates)
14
ATU

12 MIC
(mg/L)
10 ≥8
No of observations

4
8 2
1
6 0.5
0.25
4 0.125
0.06
2 ≤0.03

0
10
12
14
16
18
20
22
24
26
28
30
32
34
36
38
40
42
44
46
48
50
6
8

Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤0.25, R>0.5 mg/L 0.5 mg/L
Zone diameter S≥25, R<22 mm 22-24 mm
Pseudomonas spp.
 Piperacillin 30 µg vs. MIC
P. aeruginosa, 236 isolates (326 correlates)
50
ATU
45
MIC
40 (mg/L)

35 ≥256
No of observations

128
30
64
25 32
16
20
8
15 4
10 2
≤1
5

0
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤0.001, R>16 mg/L
Zone diameter S≥50, R<18 mm 18-19 mm
 Piperacillin 30 µg vs. MIC
Pseudomonas non-aeruginosa, 171 isolates
16
ATU
14
MIC
12 (mg/L)
No of observations

≥128
10 64
32
8
16
6 8
4
4 2
≤1
2

0
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤0.001, R>16 mg/L
Zone diameter S≥50, R<18 mm 18-19 mm
 Piperacillin-tazobactam 30-6 µg vs. MIC
P. aeruginosa, 217 isolates (376 correlates)
60
ATU

MIC
50
(mg/L)

≥128
No of observations

40
64
32
30 16
8
4
20
2
1
10 ≤0.5

0
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤0.001, R>16 mg/L
Zone diameter S≥50, R<18 mm 18-19 mm
 Piperacillin-tazobactam 30-6 µg vs. MIC
Pseudomonas non-aeruginosa, 191 isolates
20
ATU
18
MIC
16 (mg/L)

14 ≥128
No of observations

64
12
32
10 16
8
8
4
6 2
4 1
≤0.5
2

0
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤0.001, R>16 mg/L
Zone diameter S≥50, R<18 mm 18-19 mm
 Ceftazidime-avibactam 10-4 µg vs. MIC
P. aeruginosa, 100 isolates (690 correlates)
180
ATU
160
MIC
140 (mg/L)

120 ≥128
No of isolates

64
100 32
80 16
8
60 4
2
40
1
20

0
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤8, R>8 mg/L
Zone diameter S≥17, R<17 mm 16-17 mm
Staphylococcus spp.
 Cefoxitin 30 µg vs. mecA status
S. epidermidis, 100 isolates (193 correlates)
20
ATU
18

16

14
No of observations

mecA
12 status
10 Positive
Negative
8

0
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints ATU
Zone diameter (screen) S≥25, R<25 mm 25-27 mm
 Ceftaroline 5 µg vs. MIC
S. aureus, 216 isolates (593 correlates)
90
ATU
80
MIC
70
(mg/L)
No of observations

60 8
4
50 2
40 1
0.5
30 0.25
0.125
20
0.06
10

0
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints (non-pneumonia) ATU

MIC S≤1, R>2 mg/L 1 mg/L
Zone diameter S≥20, R<17 mm 19-20 mm
 Ceftaroline 5 µg vs. MIC
S. aureus, 216 isolates (593 correlates)
90
ATU
80
MIC
70
(mg/L)
No of observations

60 8
4
50 2
40 1
0.5
30 0.25
0.125
20
0.06
10

0
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints (pneumonia) ATU

MIC S≤1, R>1 mg/L 1 mg/L
Zone diameter S≥20, R<20 mm 19-20 mm
 Ceftobiprole 5 µg vs. MIC
S. aureus, 114 isolates (228 correlates)
30
ATU

25
MIC
(mg/L)
No of observations

20
4
2
15
1
0.5
10 0.25
0.125
5

0
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤2, R>2 mg/L 2 mg/L
Zone diameter S≥17, R<17 mm 16-17 mm
 Amikacin 30 µg vs. MIC
S. aureus, 173 isolates (312 correlates)
45
ATU
40
Resistance to amikacin is most reliably
determined by testing with kanamycin
35 (R>8 mg/L or R<18 mm).
MIC
No of observations

30 (mg/L)
≥64
25 32
20 16
8
15 4
≤2
10

0
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤8, R>8 mg/L
Zone diameter S≥18, R<18 mm 16-19 mm
Haemophilus influenzae
 Piperacillin-tazobactam 30-6 µg vs. MIC
H. influenzae, 161 isolates (171 correlates)
25
ATU

20
MIC
No of observations

(mg/L)
15 0.5
0.25
0.125
10 0.06
0.03
≤0.016
5

0
10
12
14
16
18
20
22
24
26
28
30
32
34
36
38
40
42
44
46
48
50
6
8

Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤0.25, R>0.25 mg/L
Zone diameter S≥27, R<27 mm 24-27 mm
 Cefepime 30 µg vs. MIC
H. influenzae, 161 isolates (172 correlates)
25
ATU

20
MIC
(mg/L)
No of observations

2
15
1
0.5
0.25
10
0.125
0.06
5 0.03

0
10
12
14
16
18
20
22
24
26
28
30
32
34
36
38
40
42
44
46
48
50
6
8

Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤0.25, R>0.25 mg/L
Zone diameter S≥28, R<28 mm 28-33 mm
 Cefotaxime 5 µg vs. MIC
H. influenzae, 210 isolates (333 correlates)
40
ATU
35 MIC
(mg/L)
30
1
No of observations

25 0.5
0.25
20 0.125
0.06
15 0.03
0.016
10
0.008
5 ≤0.004

0
10
12
14
16
18
20
22
24
26
28
30
32
34
36
38
40
42
44
46
48
50
6
8

Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤0.125, R>0.125 mg/L
Zone diameter S≥27, R<27 mm 25-27 mm
 Cefpodoxime 10 µg vs. MIC
H. influenzae, 146 isolates
25
ATU

MIC
20 (mg/L)
≥8
No of observations

4
15
2
1
0.5
10
0.25
0.125
5 0.06
0.03

0
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤0.25, R>0.25 mg/L
Zone diameter S≥26, R<26 mm 26-29 mm
 Cetriaxone 30 µg vs. MIC
H. influenzae, 152 isolates (172 correlates)
25
ATU

20
MIC
(mg/L)
0.25
15
No of observations

0.125
0.06
0.03
10
0.016
0.008
5 ≤0.004

0
10
12
14
16
18
20
22
24
26
28
30
32
34
36
38
40
42
44
46
48
50
6
8

Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤0.125, R>0.125 mg/L
Zone diameter S≥32, R<32 mm 31-33 mm
 Cefuroxime 30 µg vs. MIC
H. influenzae, 159 isolates (180 correlates)
18
ATU
16
MIC
14
(mg/L)
No of observations

12 ≥32
16
10 8
8 4
2
6 1
0.5
4
0.25
2

0
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints (iv) ATU

MIC S≤1, R>2 mg/L 2 mg/L
Zone diameter S≥27, R<25 mm 25-27 mm
 Cefuroxime 30 µg vs. MIC
H. influenzae, 159 isolates (180 correlates)
18
ATU
16
MIC
14
(mg/L)
No of observations

12 ≥32
16
10 8
8 4
2
6 1
0.5
4
0.25
2

0
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints (oral) ATU

MIC S≤0.001, R>1 mg/L
Zone diameter S≥50, R<27 mm 25-27 mm
 Imipenem 10 µg vs. MIC
H. influenzae, 150 isolates (162 correlates)
30
ATU

25 MIC
(mg/L)
No of observations

20 8
4
2
15
1
0.5
10 0.25
0.125
5 ≤0.06

0
10

12

14

16

18

20

22

24

26

28

30

32

34

36

38

40
6

Inhibition zone diameter (mm)

Breakpoints ATU
MIC S≤2, R>2 mg/L
Zone diameter S≥20, R<20 mm 6-19 mm