European Committee on Antimicrobial Susceptibility Testing

European Committee on Antimicrobial Susceptibility Testing Breakpoint tables for interpretation of MICs and zone diameters Version 2.0, valid from 2012-01-01 Content

Page

Notes Changes Enterobacteriaceae Pseudomonas spp. Stenotrophomonas maltophilia Acinetobacter spp. Staphylococcus spp. Enterococcus spp. Streptococcus groups A, B, C and G Streptococcus pneumoniae Viridans group streptococci Haemophilus influenzae Moraxella catarrhalis Neisseria gonorrhoeae Neisseria meningitidis Gram-positive anaerobes Clostridium difficile Gram-negative anaerobes Helicobacter pylori Listeria monocytogenes Non-species related breakpoints

1 2 3 8 12 13 17 22 27 32 37 41 46 50 54 58 62 63 67 68 69

European Committee on Antimicrobial Susceptibility Testing Breakpoint tables for interpretation of MICs and zone diameters Version 2.0, valid from 2012-01-01 Notes 1. The EUCAST tables of clinical breakpoints contain clinical MIC breakpoints (determined over the period 2002-2011) and their inhibition zone diameter correlates. The EUCAST breakpoint table version 2.0 includes corrected typographical errors, clarifications, breakpoints for new organisms, revised MIC breakpoints and revised and new zone diameter breakpoints. Changes are best seen on screen or on a colour printout since cells containing a change are yellow. 2. Non-species-related breakpoints (Pk/Pd breakpoints) are listed separately on the last page. 3. Numbered footnotes relate to MIC breakpoints. Lettered footnotes relate to zone diameter breakpoints. 4. Highlighted antimicrobial names link to EUCAST rationale documents. Highlighted MIC breakpoints and zone diameter breakpoints link to EUCAST MIC and zone diameter distributions, respectively. 5. One version of the document is released as an unprotected Excel file to enable users to alter the list of agents to suit the range of agents tested locally and to present breakpoints in the format used locally. The content of single cells cannot be changed. Hide lines by right-clicking on the line number and choosing "hide". Hide columns by right-clicking on the column letter and choosing "hide". If you wish to add the intermediate columns for MICs and/or zone diameters right-click on the column letter and choose "insert". The intermediate values are inferred from the "S" and "R" breakpoints. 6. A zone diameter breakpoint of "S ≥ 50 mm" is an arbitrary "off scale" zone diameter breakpoint corresponding to MIC breakpoint situations where wild type isolates are categorised as intermediate (i.e. no fully susceptible isolates exist). 7. In order to simplify the EUCAST tables, the intermediate category is not listed. It is readily interpreted as the values between the S and the R breakpoint. For example, for MIC breakpoints listed as S ≤ 1 mg/L and R > 8 mg/L, the intermediate category is 2-8 (technically >1-8) mg/L, and for zone diameter breakpoints listed as S ≥ 22 mm and R < 18 mm, the intermediate category is 18-21 mm.

"-" indicates that susceptibility testing is not recommended as the species is a poor target for therapy with the drug. Isolates may be reported as R without prior testing. "IE" indicates that there is insufficient evidence that the species in question is a good target for therapy with the drug. An MIC with a comment but without an accompanying S, I or R categorisation may be reported. NA = Not Applicable IP = In Preparation

1

European Committee on Antimicrobial Susceptibility Testing Breakpoint tables for interpretation of MICs and zone diameters Version 2.0, valid from 2012-01-01 Table

Changes (cells containing a change, a deletion or an addition) from v 1.3 are marked yellow

All

• Instructions for disk diffusion methodology and quality control included. • Typo error on trimethoprim-sulfamethoxazole corrected to 1.25-23.75 µg. • Telavancin breakpoints added.

Enterobacteriaceae

• Revised breakpoints: Ampicillin, ampicillin-sulbactam, amoxicillin, amoxicillin-clavulanate, piperacillin-tazobactam, cefotaxime, ceftibuten, imipenem and tobramycin. Ticarcillin and ticarcillinclavulanate (typo errors). • Disk content (30 μg) for cefoxitin added. • Ceftibuten: "uncomplicated UTI only" is changed to "UTI only". • Revised comments: Penicillins, ampicillin, mecillinam comment F and imipenem.

Pseudomonas spp.

• Revised breakpoints: Doripenem and fosfomycin. Trimethoprim-sulfamethoxazole breakpoint for Stenotrophomonas maltophilia moved to a separate table. • Revised comment: Fosfomycin. • New table. • Revised comments: Trimethoprim-sulfamethoxazole. • Revised breakpoints: Vancomycin (specific breakpoints for S. aureus and coagulase-negative staphylococci). • Revised comments: Penicillins, glycopeptides and doxycycline. • Revised breakpoints: Mupirocin. • Revised comments: Penicillins, amoxicillin-clavulanate and nitrofurantoin. General recommendation for endocarditis added. • Revised breakpoints: Mupirocin and trimethoprim. • Revised comments: Benzylpenicillin, phenoxymethylpenicillin, doxycycline and trimethoprim. • Typo error on benzylpenicillin note corrected. Correct dosages are 1.2 and 2.4 g. • Revised breakpoints: Ceftibuten, linezolid (typo error on MIC breakpoint) and mupirocin. • Revised comments: Penicillins (several comments merged), benzylpenicillin, ampicillin, ampicillin-sulbactam, phenoxymethylpenicillin and doxycyline. Benzylpenicillin and meropenem (breakpoints for meningitis moved to a separate row).

Stenotrophomonas maltophilia Staphylococcus spp. Enterococcus spp. Streptococcus groups A, B, C and G Stretococcus pneumoniae

Viridans group streptococci (Other streptococci) Haemophilus influenzae

• "Other streptococci" changed to "Viridans group streptococci". General recommendation for endocarditis added. • Revised breakpoints: Benzylpenicillin (screen) and mupirocin. • Revised breakpoints: Benzylpenicillin (screen), amoxicillin, amoxicillin-clavulanate, phenoxymethylpenicillin (screen breakpoint removed), cefepime, cefixime, cefotaxime, cefpodoxime, ceftibuten, ceftriaxone, cefuroxime, cefuroxime-axetil, imipenem, ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin, minocycline, tetracycline, chloramphenicol and rifampicin. • Disk content for amoxicillin-clavulanate changed to 2-1 µg. • Revised comments: Benzylpenicillin, ampicillin, piperacillin, cefaclor, meropenem and doxycycline.

Moraxella catarrhalis

• Revised breakpoints: Ampicillin, amoxicillin, amoxicillin-clavulanate, piperacillin, cefaclor, cefepime, cefixime, cefpodoxime, ceftibuten, cefuroxime, cefuroxime-axetil, azithromycin, chloramphenicol and rifampicin. • Disk content for amoxicillin-clavulanate changed to 2-1 µg. • Revised comments: Cefaclor and doxycycline.

Neisseria gonorrhoeae

• Revised comment: Doxycycline.

Gram-positive anaerobes

• New comment: Ampicillin-sulbactam, amoxicillin-clavulanate, piperacillin-tazobactam and ticarcillin-clavulanate.

Clostridium difficile

• New table. All breakpoints and comments new.

Gram-negative anaerobes Miscellaneous

• Revised breakpoints: Teicoplanin. • New comment: Ampicillin-sulbactam, amoxicillin-clavulanate, piperacillin-tazobactam and ticarcillin-clavulanate. • Table removed. Organisms with breakpoints have new tables.

Helicobacter pylori

• New table. All breakpoints and comments new.

Listeria monocytogenes

• New table. All breakpoints new.

Non-species related

• Revised breakpoints: Nalidixic acid, vancomycin and teicoplanin. • Revised comments: Teicoplanin and vancomycin. • "Uncomplicated UTI only" removed from antibiotic names.

2

EUCAST Clinical Breakpoint Table v. 2.0, valid from 2012-01-01

Enterobacteriaceae

Disk diffusion (EUCAST standardised disk diffusion method) Medium: Mueller-Hinton agar Inoculum: McFarland 0.5 Incubation: Air, 35±1ºC, 18±2h Reading: Read zone edges as the point showing no growth viewed from the back of the plate against a black background illuminated with reflected light. Quality control: Escherichia coli ATCC 25922

Penicillins1

MIC breakpoint (mg/L) S≤

R>

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) S≥ R

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) S≥ R< 1. The cephalosporin breakpoints for Enterobacteriaceae will detect all clinically important resistance mechanisms (including ESBL and plasmid mediated AmpC). Some isolates that produce beta-lactamases are susceptible or intermediate to 3rd or 4th generation cephalosporins with these breakpoints and should be reported as tested, i.e. the presence or absence of an ESBL does not in itself influence the categorisation of susceptibility. In many areas, ESBL detection and characterisation is recommended or mandatory for infection control purposes.

-

-

-

-

Cefadroxil (uncomplicated UTI only)

16

16

30

12

12

Cefalexin (uncomplicated UTI only) Cefazolin

16

16

30

12

12

-

-

Cefepime

1

4

Cefixime (uncomplicated UTI only)

1

Cefotaxime

1

Cefaclor

-

-

30

24

21

1

5

17

17

2

5

20

17

NA

NA

30

19

19

Cefpodoxime (uncomplicated UTI only)

1

1

10

21

21

Ceftazidime

1

4

10

22

19

Ceftibuten (UTI only)

1

1

30

23

23

Ceftriaxone

1

2

30

23

20

Cefuroxime

83 8

8

30

18

18

8

30

18

18

Cefoxitin (screen)2

Cefuroxime axetil (uncomplicated UTI only)

Carbapenems1


R>

2. The cefoxitin ECOFF (WT ≤ 8 mg/L) has a high sensitivity, but poor specificity for identification of AmpC-producing Enterobacteriaceae as this antibiotic is also affected by permeability alterations and some carbapenemases. Classical non-AmpC producers are wild type, whereas plasmid AmpC producers or chromosomal AmpC hyperproducers are non-wild type.

3. The breakpoint relates to a dosage of 1.5 g x 3 and to E. coli, P. mirabilis and Klebsiella spp. only.

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) S≥ R< 1. The carbapenem breakpoints for Enterobacteriaceae will detect all clinically important resistance mechanisms (including the majority of carbapenemases). Some isolates that produce carbapenemase are categorised as susceptible with these breakpoints and should be reported as tested, i.e. the presence or absence of a carbapenemase does not in itself influence the categorisation of susceptibility. In many areas, carbapenemase detection and characterisation is recommended or mandatory for infection control purposes.

Doripenem

1

4

10

24

18

Ertapenem

0.5

1

10

25

22

Imipenem2 Meropenem

2

8

10

22

16

2

8

10

22

16

2. Low-level resistance is common in Morganella spp., Proteus spp. and Providencia spp.

4


Enterobacteriaceae Monobactams

Aztreonam1

Fluoroquinolones


R>

1

4

MIC breakpoint (mg/L)

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) S≥ R< 30

27

24


0.5

1

5

22

19

Levofloxacin

1

2

5

22

19

Moxifloxacin

0.5

1

5

20

17

Nalidixic acid (screen)

NA

NA

NA

NA

Norfloxacin

0.5

1

10

22

19

Ofloxacin

0.5

1

5

22

19

Ciprofloxacin1

Aminoglycosides1


R>

1. The aztreonam breakpoints for Enterobacteriaceae will detect clinically important resistance mechanisms (including ESBL). Some isolates that produce beta-lactamases are susceptible or intermediate to 3rd or 4th generation cephalosporins with these breakpoints and should be reported as tested, i.e. the presence or absence of an ESBL does not in itself influence the categorisation of susceptibility. In many areas, ESBL detection and characterisation is recommended or mandatory for infection control purposes.

1. Salmonella spp. - there is clinical evidence for ciprofloxacin to indicate a poor response in systemic infections caused by Salmonella spp. with low-level fluoroquinolone resistance (MIC>0.06 mg/L). The available data relate mainly to S. typhi but there are also case reports of poor response with other Salmonella species.

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) S≥ R< 1. Aminoglycoside breakpoints are based on once-daily administration of high aminoglycoside dosages. Most often aminoglycosides are given in combination with beta-lactam agents.

Amikacin

8

16

30

16

13

Gentamicin

2

4

10

17

14

Netilmicin

2

4

10

15

12

Tobramycin

2

4

10

17

14

5


Enterobacteriaceae Glycopeptides



-

-

-

-

Telavancin

-

-

-

Vancomycin

-

-

-

-

Teicoplanin

Macrolides, lincosamides and streptogramins



Azithromycin1

-

-

-

-

Clarithromycin

-

-

-

-

Erythromycin1 Roxithromycin

-

-

-

-

-

-

-

-

Telithromycin

-

-

-

-

Clindamycin

-

-

-

-

Quinupristin-dalfopristin

-

-

-

-

1. Azithromycin has been used in the treatment of infections with Salmonella typhi (MIC ≤16 mg/L for wild type isolates) and Shigella spp.

6


Enterobacteriaceae Tetracyclines



Doxycycline

-

-

-

-

Minocycline

-

-

-

-

Tetracycline

-

-

-

-

Tigecycline1

1

2

18A

15A

Miscellaneous agents


R>

Chloramphenicol

8

8

Colistin

2

2

Daptomycin

-

Fosfomycin iv Fosfomycin-trometamol (uncomplicated UTI only)

15


17

-

NoteA -

NoteA -

32

32

-

-

32

32

-

-

Fusidic acid

-

-

-

-

Linezolid

-

-

-

-

Metronidazole

-

-

-

-

Mupirocin

-

-

-

-

641 -

641 -

100

11B -

11B -

Nitrofurantoin (uncomplicated UTI only) Rifampicin

1. Tigecycline has decreased activity against Morganella spp., Proteus spp. and Providencia spp. A. Zone diameter breakpoints validated for E. coli only. For other Enterobacteriaceae, use an MIC method.

30

Spectinomycin

-

-

-

-

Trimethoprim (uncomplicated UTI only)

2

4

5

18

15

Trimethoprim-sulfamethoxazole2

2

4

1.25-23.75

16

13

A. Use an MIC method.

1/B. Breakpoints relate to E. coli only.

2. Trimethoprim:sulfamethoxazole in the ratio 1:19. Breakpoints are expressed as the trimethoprim concentration.

7


Pseudomonas spp.

Disk diffusion (EUCAST standardised disk diffusion method) Medium: Mueller-Hinton agar Inoculum: McFarland 0.5 Incubation: Air, 35±1ºC, 18±2h Reading: Read zone edges as the point showing no growth viewed from the back of the plate against a black background illuminated with reflected light. Quality control: Pseudomonas aeruginosa ATCC 27853

Penicillins


Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) R< S≥

S≤

R>

Benzylpenicillin Ampicillin

-

-

-

-

Ampicillin-sulbactam

-

-

-

-

Amoxicillin

-

-

-

-

Amoxicillin-clavulanate

-

-

-

-

Piperacillin1 Piperacillin-tazobactam1 Ticarcillin3 Ticarcillin-clavulanate3

16 162 16

16 162 16

162

162

19 19 17 17

19 19 17 17

Phenoxymethylpenicillin

-

-

-

-

Oxacillin

-

-

-

-

Cloxacillin

-

-

-

-

Dicloxacillin

-

-

-

-

Flucloxacillin

-

-

-

-

Mecillinam (uncomplicated UTI only)

-

-

-

-

30 30-6 75 75-10

1. Breakpoints are based on high dose therapy (with or without tazobactam, 4 g x 4). 2. For susceptibility testing purposes, the concentration of beta-lactamase inhibitor is fixed at 4 mg/L. 3. Breakpoints are based on high dose therapy (with or without clavulanate, 3 g x 4).

8


Pseudomonas spp. Cephalosporins



S≤

R>

Cefaclor

-

-

-

-

Cefadroxil

-

-

-

-

Cefalexin

-

-

-

-

Cefazolin

-

-

-

-

Cefepime

81 -

8

18

18

-

-

Cefixime Cefotaxime Cefoxitin

-

-

-

-

-

NA

NA

NA

NA

Cefpodoxime

-

-

Ceftazidime

8

Ceftibuten

81 -

Ceftriaxone

-

Cefuroxime

-

Cefuroxime axetil

-

Carbapenems

-

-

-

16 -

16 -

-

-

-

-

-

-

-

-

-


R>

Doripenem

1

4

Ertapenem

-

-

Imipenem Meropenem

41 2

8 8

Monobactams

Aztreonam

30


R>

1

161

10

1. Breakpoints relate to high dose therapy (2 g x 3).

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) R< S≥ 10 10 10

25

19

-

-

20 24

17 18

1. Breakpoints relate to high dose, frequent therapy (1 g x 4).

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) R< S≥ 30

50

16

1. The resistant breakpoint relates to high dose therapy. The susceptible breakpoint is set to ensure that wild type isolates are reported intermediate.

9


Pseudomonas spp. Fluoroquinolones

Ciprofloxacin Levofloxacin


R>

0.5 1

1 2

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) R< S≥ 5 5

25 20

22 17

-

-

-

-

NA

NA

NA

NA

Norfloxacin

-

-

-

-

Ofloxacin

-

-

-

-

Moxifloxacin Nalidixic acid (screen)

Aminoglycosides1


R>

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) R< S≥ 1. Aminoglycoside breakpoints are based on once-daily administration of high aminoglycoside dosages. Most often aminoglycosides are given in combination with beta-lactam agents.

Amikacin

8

16

30

18

15

Gentamicin

4

4

10

15

15

Netilmicin

4

4

10

12

12

Tobramycin

4

4

10

16

16

Glycopeptides



S≤

R>

-

-

-

-

Telavancin

-

-

-

Vancomycin

-

-

-

-

Teicoplanin

10


Pseudomonas spp. Macrolides, lincosamides and streptogramins



S≤

R>

Azithromycin

-

-

-

-

Clarithromycin

-

-

-

-

Erythromycin

-

-

-

-

Roxithromycin

-

-

-

-

Telithromycin

-

-

-

-

Clindamycin

-

-

-

-


-

-

-

-

Tetracyclines



S≤

R>

Doxycycline

-

-

-

-

Minocycline

-

-

-

-

Tetracycline

-

-

-

-

Tigecycline

-

-

-

-

Miscellaneous


R>


Chloramphenicol

-

-

-

-

Colistin

4

4

Daptomycin

-

-

NoteA -

NoteA -

Fosfomycin iv1

-

-

-

-

Fosfomycin-trometamol (uncomplicated UTI only)

-

-

-

-

Fusidic acid

-

-

-

-

Linezolid

-

-

-

-

Metronidazole

-

-

-

-

Mupirocin Nitrofurantoin (uncomplicated UTI only)

-

-

-

-

Rifampicin

-

-

-

-

Spectinomycin

-

-

-

-


-

-

-

-

Trimethoprim-sulfamethoxazole

-

-

-

-

A. Use an MIC method. 1. Anecdotal evidence suggests that infections caused by wild type isolates (ECOFF: WT ≤ 128 mg/L) may be treated with combinations of fosfomycin and other agents.

11


Stenotrophomonas maltophilia

Disk diffusion (EUCAST standardised disk diffusion method) Medium: Mueller-Hinton agar Inoculum: McFarland 0.5 Incubation: Air, 35±1ºC, 18±2h Reading: Read zone edges as the point showing no growth viewed from the back of the plate against a black background illuminated with reflected light. Quality control: Escherichia coli ATCC 25922

Antibiotic agent



R>

4

4

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) R< S≥ 1.25-23.75

16A

16A

1. Trimethoprim:sulfamethoxazole in the ratio 1:19. Breakpoints are expressed as the trimethoprim concentration. A. Ignore haze or fine growth within the inhibition zone.

12


Acinetobacter spp.

Disk diffusion (EUCAST standardised disk diffusion method) Medium: Mueller-Hinton agar Inoculum: McFarland 0.5 Incubation: Air, 35±1ºC, 18±2h Reading: Read zone edges as the point showing no growth viewed from the back of the plate against a black background illuminated with reflected light. Quality control: Pseudomonas aeruginosa ATCC 27853

Penicillins1


R>

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) R< S≥ 1. Susceptibility testing of Acinetobacter spp. to penicillins is unreliable. In most instances Acinetobacter spp. are resistant to penicillins.

Benzylpenicillin

-

-

-

Ampicillin

-

-

-

-


IE

IE

IE

IE

Amoxicillin

-

-

-

-


-

-

-

-

Piperacillin

IE

IE

IE

IE

Piperacillin-tazobactam

IE

IE

IE

IE

Ticarcillin

IE

IE

IE

IE

Ticarcillin-clavulanate

IE

IE

IE

IE


-

-

-

-

Oxacillin

-

-

-

-

Cloxacillin

-

-

-

-

Dicloxacillin

-

-

-

-

Flucloxacillin

-

-

-

-


-

-

-

-

-

13


Acinetobacter spp. Cephalosporins



S≤

R>

Cefaclor

-

-

-

-

Cefadroxil

-

-

-

-

Cefalexin

-

-

-

-

Cefazolin

-

-

-

-

Cefepime

-

-

-

-

Cefixime

-

-

-

-

Cefotaxime

-

-

-

-

Cefoxitin

-

-

-

-

Cefpodoxime

-

-

-

-

Ceftazidime

-

-

-

-

Ceftibuten

-

-

-

-

Ceftriaxone

-

-

-

-

Cefuroxime

-

-

-

-

Cefuroxime axetil

-

-

-

-

Carbapenems


R>

Doripenem

1

4

Ertapenem

-

-

Imipenem

2

8

Meropenem

2

8

Monobactams

Aztreonam


R>

-

-

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) R< S≥ 10

21

15

-

-

10

23

17

10

21

15

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) S≥ R< -

-

14


Acinetobacter spp. Fluoroquinolones



Ciprofloxacin

1

1

5

21

21

Levofloxacin

1

2

5

21

18

Moxifloxacin

-

-

-

-

NA -

NA -

NA -

NA -

-

-

-

-

Nalidixic acid (screen) Norfloxacin Ofloxacin

Aminoglycosides1


R>

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) S≥ R< 1. Aminoglycoside breakpoints are based on once-daily administration of high aminoglycoside dosages. Most often aminoglycosides are given in combination with beta-lactam agents.

Amikacin

8

16

30

18

15

Gentamicin

4

4

10

17

17

Netilmicin

4

4

10

16

16

Tobramycin

4

4

10

17

17

Glycopeptides



-

-

-

-

Telavancin

-

-

-

Vancomycin

-

-

-

-

Teicoplanin

15


Acinetobacter spp. Macrolides, lincosamides and streptogramins



Azithromycin

-

-

-

-

Clarithromycin

-

-

-

-

Erythromycin

-

-

-

-

Roxithromycin

-

-

-

-

Telithromycin

-

-

-

-

Clindamycin

-

-

-

-


-

-

-

-

Tetracyclines


R>



Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) S≥ R< 1/A. Most staphylococci are penicillinase producers. The benzylpenicillin breakpoint will mostly, but not unequivocally, separate beta-lactamase producers from non-producers. If the MIC is >0.12 mg/L, report resistant. If the MIC is ≤0.12mg/L, test susceptibility with a disk diffusion test (see note B). Isolates positive for beta-lactamase are resistant to benzylpenicillin, phenoxymethylpenicillin, amino-, carboxy- and ureidopenicillins. Isolates negative for beta-lactamase and susceptible to cefoxitin (cefoxitin is used to screen for “methicillin resistance”) can be reported susceptible to these drugs. Isolates positive for beta-lactamase and susceptible to cefoxitin are susceptible to penicillin-beta-lactamase inhibitor combinations and penicillinase-resistant penicillins (oxacillin, cloxacillin, dicloxacillin and flucloxacillin). Isolates resistant to cefoxitin are methicillin resistant and resistant to beta-lactam agents, except those with approved anti-MRSA activity and clinical breakpoints.

Benzylpenicillin

0.121

0.121,2

1 unit

26A,B

26A,B

B. Disk diffusion is more reliable than MIC for detection of penicillinase producers, provided the zone diameter is measured AND the zone edge closely inspected. If the zone diameter is 2 mg/L are mostly methicillin resistant due to the presence of the mecA gene. The corresponding oxacillin MIC for coagulase-negative staphylococci is >0.25 mg/L.

17


Staphylococcus spp. Cephalosporins1


R>

4 mg/L are mostly methicillin resistant due to the presence of the mecA gene. For coagulase-negative staphylococi other than S. lugdunensis the cefoxitin MIC is a poorer predictor of methicillin resistance than the disk diffusion test.

25A A

Ceftibuten

Cefuroxime axetil

1. Susceptibility of staphylococci to cephalosporins is inferred from the cefoxitin susceptibility except for ceftazidime, cefixime and ceftibuten, which do not have breakpoints and should not be used for staphylococcal infections. 2. High-dose therapy is required for treatment of staphylococcal infections. A. Susceptibility inferred from cefoxitin.


Doripenem

Note1

Note1

NoteA

NoteA

Ertapenem Imipenem Meropenem

Note1 Note1 Note1

Note1 Note1 Note1

NoteA NoteA NoteA

NoteA NoteA NoteA

1/A. Susceptibility of staphylococci to carbapenems is inferred from the cefoxitin susceptibility.

18


Staphylococcus spp. Monobactams

Aztreonam

Fluoroquinolones1


R>

-

-


Ciprofloxacin2 Levofloxacin

R>


-


1. Regarding breakpoints for other fluoroquinolones (e.g. pefloxacin and enoxacin) - refer to breakpoints determined by national breakpoint committees. 2. Breakpoints relate to high dose therapy.

A. The norfloxacin disk diffusion test can be used to screen for fluoroquinolone resistance. Isolates categorised as susceptible can be reported susceptible to ciprofloxacin, levofloxacin, moxifloxacin and ofloxacin. Isolates categorised as resistant should be tested for susceptibility to individual agents.


Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) S≥ R< 1. Glycopeptide MICs are method dependent and should be determined by broth microdilution (reference ISO 20776). S. aureus with vancomycin MIC values of 2 mg/L are on the border of the wild type MIC distribution and there may be an impaired clinical response. The resistant breakpoint has been reduced to 2 mg/L to avoid reporting "GISA" isolates intermediate as serious infections with "GISA" isolates are not treatable with increased doses of vancomycin or teicoplanin.

Teicoplanin, S. aureus Teicoplanin, Coagulase-negative staphylococci

2 4

2 4

NoteA NoteA

NoteA NoteA

Telavancin, MRSA

1

1

NoteA

NoteA

Vancomycin, S. aureus Vancomycin, Coagulase-negative staphylococci

2 4

2 4

A

NoteA NoteA



Note NoteA


11

21

NoteA

NoteA

1

1 1

1

2 2

A

NoteA 18

Telithromycin

11 IE

21 IE

NoteA IE

NoteA IE

Clindamycin2

0.25

0.5

2

22B

19B

1

2

15

21C

18C

Azithromycin Clarithromycin Erythromycin Roxithromycin


Tetracyclines


R>

Doxycycline

11

21

Minocycline

0.51

11

Tetracycline

11

21 0.5

Tigecycline

0.5

2

A. Disk diffusion is unreliable and cannot distinguish between wild type isolates and those with non-vanA -mediated resistance.

15

Note 21

1/A. Erythromycin can be used to determine susceptibility to azithromycin, clarithromycin and roxithromycin.

2/B. Inducible clindamycin resistance can be detected only in the presence of a macrolide antibiotic. In disk diffusion tests look for apparent antagonism of clindamycin by erythromycin (D-test). C. Isolates non-susceptible by disk diffusion should be confirmed by MIC testing.

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) S≥ R< NoteA

NoteA

30

23A

20A

30

22A 18

19A 18

15

1/A. Isolates susceptible to tetracycline are also susceptible to doxycycline and minocycline, but some resistant to tetracycline may be susceptible to minocycline and/or doxycycline. An MIC method should be used to test doxycycline susceptibility of tetracycline resistant isolates if required.

2. Isolates with MIC values above the susceptible breakpoint are very rare or not yet reported. The identification and antimicrobial susceptibility tests on any such isolate must be repeated and if the result is confirmed the isolate sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC values above the current resistant breakpoint they should be reported resistant.

20


Staphylococcus spp. Miscellaneous



Chloramphenicol

8

8

Colistin

-

-

-

Daptomycin

1

11

NoteA

NoteA

Fosfomycin iv

NoteA -

NoteA -

30

18

18

32

32


-

-

Fusidic acid

1

1

10

24

24

Linezolid

4

4

10

19

19

Metronidazole

-

-

Mupirocin

12

2562

643 0.06

643 0.5

Spectinomycin

-

-


2


2

Nitrofurantoin (uncomplicated UTI only) Rifampicin

-

-

200

30B

18B

100 5

13C 26

13C 23

-

-

4

5

17

14

4

1.25-23.75

17

14

1. Isolates with MIC values above the susceptible breakpoint are very rare or not yet reported. The identification and antimicrobial susceptibility tests on any such isolate must be repeated and if the result is confirmed the isolate sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC values above the current resistant breakpoint they should be reported resistant. A. Use an MIC method.

2/B. Breakpoints relate to nasal decolonisation of S. aureus. Intermediate isolates are initially cleared as effectively as susceptible isolates but recolonisation is very common. 3/C. Breakpoints relate to S. saprophyticus only.


21


Enterococcus spp. In endocarditis, refer to national or international endocarditis guidelines for breakpoints for Enterococcus spp.

Penicillins1

Disk diffusion (EUCAST standardised disk diffusion method) Medium: Mueller-Hinton agar Inoculum: McFarland 0.5 Incubation: Air, 35±1ºC, 18±2h Reading: Read zone edges as the point showing no growth viewed from the back of the plate against a black background illuminated with reflected light. Quality control: Enterococcus faecalis ATCC 29212



Benzylpenicillin

-

-

Ampicillin

4

8

10

8

Ampicillin-sulbactam2

4

8

NoteA

NoteA

Amoxicillin2 Amoxicillin-clavulanate2

4

8

43

83

NoteA NoteA

NoteA NoteA

Piperacillin2

Note2

Note2

NoteA

NoteA

Piperacillin-tazobactam2 Ticarcillin

Note2 -

Note2 -

NoteA -

NoteA -


-

-

-

-


-

-

-

-

Oxacillin

-

-

-

-

Cloxacillin

-

-

Dicloxacillin

-

-

-

-

Flucloxacillin

-

-

-

-


-

-

-

-

1. E. faecium resistant to penicillins can be considered resistant to all other beta-lactam agents including carbapenems. 2

2/A. Susceptibility to ampicillin, amoxicillin and pipercillin with and without beta-lactamase inhibitor can be inferred from the ampicillin susceptibility test. 3. For susceptibility testing purposes, the concentration of clavulanate is fixed at 2 mg/L.

22


Enterococcus spp. Cephalosporins


R>

Cefaclor Cefadroxil

-

-

-

-

Cefalexin Cefazolin

-

Cefepime


-

-

-

-

-

-

-

-

-

-

Cefixime

-

-

-

-

Cefotaxime

-

-

-

-

Cefoxitin

-

-

-

-

Cefpodoxime Ceftazidime

-

-

-

-

Ceftibuten

-

-

-

-

Ceftriaxone

-

-

-

-

Cefuroxime Cefuroxime axetil

-

-

-

-

Carbapenems



Doripenem

-

-

-

Ertapenem

-

-

-

-

Imipenem

4

8

21

18

Meropenem

-

-

-

-

Monobactams

Aztreonam


R>

-

-

10

-


-

23


Enterococcus spp. Fluoroquinolones



Ciprofloxacin

-

-

-

-

Levofloxacin

-

-

-

-

Moxifloxacin

-

-

-

-

NA

NA

NA

NA

Norfloxacin

-

-

-

-

Ofloxacin

-

-

-

-


Aminoglycosides1


R>

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) S≥ R< 1. Aminoglycoside monotherapy is ineffective against enterococci. There is synergism between aminoglycosides and beta-lactam agents against enterococci without acquired aminoglycoside resistance mechanisms.

Amikacin Gentamicin

Netilmicin Streptomycin

Tobramycin

IE

IE

Note2

Note2

IE

IE

Note

IE

3

Note

IE

3

30

300

NoteA

NoteA

NoteA

NoteA

NoteA

NoteA

B

NoteB

NoteA

NoteA

Note

2/A. Isolates with gentamicin MIC >128 mg/L or an inhibition zone diameter 512 mg/L and/or an inhibition zone diameter

Teicoplanin

21

2

Telavancin

IE

IE

Vancomycin

41

4




16A

16A

IE

IE

5

12A

12A


Azithromycin

-

-

-

-

Clarithromycin

-

-

-

-

Erythromycin

-

-

-

-

Roxithromycin

-

-

-

-

Telithromycin

-

-

-

-

-

-

Clindamycin

-

-


11

41

1. The susceptible breakpoint for vancomycin has been raised to 4 mg/L to avoid dividing the wild type MIC distributions of some species. The resistant breakpoint for teicoplanin has been reduced to 2 mg/L to avoid erroneous reporting of isolates with vanA mediated resistance. A. Glycopeptide susceptible enterococci exhibit sharp zone edges. Suspect resistance when the zone edge is fuzzy or colonies grow within the inhibition zone. Some vanB isolates (vancomycin resistant, teicoplanin susceptible) are particularly difficult to detect with disk diffusion.

15

-

-

22A

20A

1/A. Quinupristin-dalfopristin breakpoints are valid for E. faecium only.

25


Enterococcus spp. Tetracyclines



Doxycycline

-

-

-

-

Minocycline

-

-

-

-

Tetracycline

-

-

-

-

Tigecycline

0.251

0.5

18

15

Miscellaneous


15



Chloramphenicol

-

-

-

Colistin

-

-

-

-

Daptomycin

IE

IE

IE

IE

Fosfomycin iv

-

-

-

-


-

-

-

-

Fusidic acid

4

-

-

Linezolid

4

19

19

Metronidazole

-

-

-

-

Mupirocin

-

-

-

-

641

641

100

-

-

15A -

15A -

0.03

1

-

-

Trimethoprim (uncomplicated UTI only)2

5

50

21

2. The activity of trimethoprim is uncertain against enterococci, hence the wild type population is categorised as intermediate.


0.03

1

1.25-23.75

50

21

3. Trimethoprim-sulfamethoxazole in the ratio 1:19. Breakpoints are expressed as the trimethoprim concentration.

Nitrofurantoin (uncomplicated UTI only) Rifampicin Spectinomycin

10

-

1/A. Nitrofurantoin breakpoints are valid for E. faecalis only.

26


Streptococcus groups A, B, C and G

Disk diffusion (EUCAST standardised disk diffusion method) Medium: Mueller-Hinton agar + 5% defibrinated horse blood and 20 mg/L β-NAD (MH-F) Inoculum: McFarland 0.5 Incubation: 5% CO2, 35±1ºC, 18±2h Reading: Read zone edges as the point showing no growth viewed from the front of the plate with the lid removed and with reflected light. Quality control: Streptococcus pneumoniae ATCC 49619

Penicillins1


R>

Benzylpenicillin2

0.25

0.25

Ampicillin

Note1


Note1

Amoxicillin Amoxicillin-clavulanate3 Piperacillin 3

Piperacillin-tazobactam Ticarcillin Ticarcillin-clavulanate



18

Note1

NoteA

NoteA

Note1

NoteA

NoteA

Note1

Note1

NoteA

NoteA

Note1

Note1

NoteA

NoteA

Note

1

Note

1

Note

A

NoteA

Note -

1

Note -

1

Note -

A

NoteA -

1 unit

-

-

-

-

Note1,4

Note1,4

NoteA,B

NoteA,B

NA

NA

NA

NA

Cloxacillin

Note1

Note1

NoteA

NoteA

Dicloxacillin

Note1

Note1

NoteA

NoteA

Flucloxacillin

Note1

Note1

NoteA

NoteA

-

-

-

-

Oxacillin


1/A. The beta-lactam susceptibility of beta-haemolytic streptococcus groups A, B, C and G is inferred from the penicillin susceptibility. 2. Isolates with MIC values above the susceptible breakpoint are very rare or not yet reported. The identification and antimicrobial susceptibility tests on any such isolate must be repeated and if the result is confirmed the isolate sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC values above the current resistant breakpoint they should be reported resistant. 3. Streptococcus groups A, B, C and G do not produce beta-lactamase. The addition of a beta-lactamase inhibitor does not add clinical benefit.

4/B. The phenoxymethylpenicillin breakpoints apply to streptococcus groups A, C and G only.

27


Streptococcus groups A, B, C and G Cephalosporins1


R>

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) S≥ R< 1/A. The beta-lactam susceptibility of beta-haemolytic streptococcus groups A, B, C and G is inferred from the penicillin susceptibility.

Cefaclor

Note1

Note1

NoteA

NoteA

Note

1

Note

A

NoteA

Note

1

Note

A

NoteA

Note

1

Cefalexin

Note

1

Cefazolin

Note1

Note1

NoteA

NoteA

Cefepime

1

1

A

NoteA -

Cefadroxil

Cefixime

Note -

Note -

Note -

Note1 NA

Note1 NA

NoteA NA

NoteA NA

Ceftazidime

Note1 -

Note1 -

NoteA -

NoteA -

Ceftibuten

Note1

Note1

NoteA

NoteA

Ceftriaxone

Note1

Note1

NoteA

NoteA

Cefuroxime

Note

1

Note

1

Note

A

NoteA

Note

1

Note

1

Note

A

NoteA

Cefotaxime Cefoxitin Cefpodoxime

Cefuroxime axetil

Carbapenems1


R>

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) S≥ R< 1/A. The beta-lactam susceptibility of beta-haemolytic streptococcus groups A, B, C and G is inferred from the penicillin susceptibility.

Doripenem

Note1

Note1

NoteA

NoteA

Ertapenem

Note1

Note1

NoteA

NoteA

Note

1

Note

1

Note

A

NoteA

Note

1

Note

1

Note

A

NoteA

Imipenem Meropenem

Monobactams

Aztreonam


R>

-

-


-

28


Streptococcus groups A, B, C and G Fluoroquinolones


R>


Teicoplanin

21

2

Telavancin

IE

IE

Vancomycin

21

2

A. The norfloxacin disk diffusion test can be used to screen for fluoroquinolone resistance. Isolates categorised as susceptible can be reported susceptible to levofloxacin and moxifloxacin. Isolates categorised as resistant should be tested for susceptibility to individual agents.


15A

15A

IE

IE

5

13A

13A

1. Isolates with MIC values above the susceptible breakpoint are very rare or not yet reported. The identification and antimicrobial susceptibility tests on any such isolate must be repeated and if the result is confirmed the isolate sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC values above the current resistant breakpoint they should be reported resistant. A. Zone diameter breakpoints are based on wild type distributions as there are currently no resistant isolates.

29


Streptococcus groups A, B, C and G Macrolides, lincosamides and streptogramins



0.251

0.51

NoteA

NoteA

1

0.25 0.25

1

0.5 0.5

15

Note 21

A

NoteA 18

Telithromycin

0.51 0.25

11 0.5

15

NoteA 22

NoteA 19

Clindamycin2

0.5

0.5

2

17B

17B

-

-

-

-

Azithromycin Clarithromycin Erythromycin Roxithromycin


Tetracyclines



2/B. Inducible clindamycin resistance can be detected only in the presence of a macrolide antibiotic. In disk diffusion tests look for apparent antagonism of clindamycin by erythromycin (D-test).


Doxycycline

11

21

Minocycline

0.51

11

30

23A

20A

Tetracycline

11

30

Tigecycline

0.252

21 0.5

23A 19

20A 16

NoteA

15

NoteA



30


Streptococcus groups A, B, C and G Miscellaneous agents



Chloramphenicol

8

8

Colistin

-

-

-

Daptomycin

11

1

NoteA

NoteA

Fosfomycin iv

-

-

-

-


-

-

-

-

Fusidic acid

IE

IE

IE

IE

Linezolid

2 -

4 -

10

19 -

16 -

-

-

100 5

15B 21

15B 15

-

-

5

IP

IP

3. Trimethoprim breakpoints apply to S. agalactiae (group B streptococci) only.

1.25-23.75

18

15


Metronidazole Mupirocin Nitrofurantoin (uncomplicated UTI only) Rifampicin

-

-

642 0.06

642 0.5

Spectinomycin

-

-


23 1

23 2


30

21

21 1. Isolates with MIC values above the susceptible breakpoint are very rare or not yet reported. The identification and antimicrobial susceptibility tests on any such isolate must be repeated and if the result is confirmed the isolate sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC values above the current resistant breakpoint they should be reported resistant. A. Use an MIC method.

2/B. Nitrofurantoin breakpoints apply to S. agalactiae (group B streptococci) only.

31


Streptococcus pneumoniae

Disk diffusion (EUCAST standardised disk diffusion method) Medium: Mueller-Hinton agar + 5% defibrinated horse blood and 20 mg/L β-NAD (MH-F) Inoculum: McFarland 0.5 from blood agar or McFarland 1.0 from chocolate agar Incubation: 5% CO2, 35±1ºC, 18±2h Reading: Read zone edges as the point showing no growth viewed from the front of the plate with the lid removed and with reflected light. Quality control: Streptococcus pneumoniae ATCC 49619

Penicillins1


R>

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) S≥ R< 1. Most MIC values for penicillin, ampicillin, amoxicillin and piperacillin (with or without a beta-lactamase inhibitor) differ by no more than one dilution step and isolates fully susceptible to benzylpenicillin (MIC ≤0.06 mg/L; susceptible by oxacillin disk screen, see note A) can be reported susceptible to beta-lactam agents that have been given breakpoints. A. Screen for beta-lactam resistance with the oxacillin 1 μg disk. Isolates categorised as susceptible can be reported susceptible to benzylpenicillin, phenoxymethylpenicillin and aminopenicillins (with or without beta-lactamase inhibitor) irrespective of clinical indication. Isolates categorised as oxacillin resistant can be reported resistant to phenoxymethylpenicillin and to benzylpenicillin in meningitis. For other beta-lactams, determine the MIC of the agent considered for clinical use.

Benzylpenicillin (infections other than meningitis)

0.061,2

21,2

1 unit

NoteA

NoteA

Benzylpenicillin (meningitis)

0.061

0.061

1 unit

NoteA

NoteA

Ampicillin

1

1


0.5 Note1

2 Note1

Amoxicillin

Note1

Amoxicillin-clavulanate Piperacillin Piperacillin-tazobactam Ticarcillin Ticarcillin-clavulanate Phenoxymethylpenicillin

2

23

A

20A

NoteA,B

NoteA,B

Note1

NoteA,B

NoteA,B

Note1

Note1

NoteA,B

NoteA,B

Note1

Note1

NoteA,B

NoteA,B

1

1

A,B

NoteA,B -

Note -

Note -

Note -

-

-

-

-

Note1

Note1

NoteA

NoteA

NA

NA

Cloxacillin

-

-

20A -

20A -

Dicloxacillin

-

-

-

-

Flucloxacillin

-

-

-

-


-

-

-

-

Oxacillin (screen)

1

2. In pneumonia, when a dose of 1.2 g x 4 is used, isolates with MIC ≤0.5 mg/L should be regarded as susceptible to benzylpenicillin. In pneumonia, when a dose of 2.4 g x 4 or 1.2 g x 6 is used, isolates with MIC ≤1 mg/L should be regarded as susceptible to benzylpenicillin. In pneumonia, when a dose of 2.4 g x 6 is used, isolates with MIC ≤2 mg/L should be regarded as susceptible.

B. Susceptibility inferred from ampicillin.

32


Streptococcus pneumoniae Cephalosporins


R>


-

-


R>


-

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) S≥ R< 1/A. The norfloxacin disk diffusion test can be used to screen for fluoroquinolone resistance. Isolates categorised as susceptible can be reported susceptible to levofloxacin and moxifloxacin and intermediate to ciprofloxacin and ofloxacin. Isolates categorised as resistant should be tested for susceptibility to individual agents.

Ciprofloxacin2

0.12

2

5

50A

18A

2. Wild type S. pneumoniae are not considered susceptible to ciprofloxacin and are therefore categorised as intermediate.

Levofloxacin3 Moxifloxacin

2

2

5

19A

19A

3. The breakpoints for levofloxacin relate to high dose therapy.

0.5

0.5

5


NA

NA

22A NA

22A NA

Norfloxacin (screen)

NA

NA

10

12A

12A

A

15A

Ofloxacin

4

Aminoglycosides

0.12

4


5

50

4. Wild type S. pneumoniae are not considered susceptible to ofloxacin and are therefore categorised as intermediate.


Amikacin

-

-

-

-

Gentamicin

-

-

-

-

Netilmicin Tobramycin

-

-

-

-

34


Streptococcus pneumoniae Glycopeptides


R>

Teicoplanin

21

2

Telavancin

IE

IE

Vancomycin

21

2




18A

18A

IE

IE

5

16A

16A


Azithromycin

0.251

0.51

NoteA

NoteA

Clarithromycin

0.251 0.25

0.51 0.5

15

NoteA 22

NoteA 19

Telithromycin

0.51 0.25

11 0.5

15

NoteA 25

NoteA 22

Clindamycin2

0.5

0.5

2

19B

19B

-

-

-

-

Erythromycin Roxithromycin




2/B. Inducible clindamycin resistance can be detected only in the presence of a macrolide antibiotic. In disk diffusion tests look for apparent antagonism of clindamycin by erythromycin (D-test).

35


Streptococcus pneumoniae Tetracyclines



Doxycycline

11

21

Minocycline

0.51

11

30

24A

21A

Tetracycline

11 IE

21 IE

30

23A IE

20A IE

Tigecycline



NoteA

NoteA


Chloramphenicol

8

8

Colistin

-

-

-

-

Daptomycin

IE

IE

IE

IE

Fosfomycin iv

IE

IE

IE

IE


-

-

-

-

Fusidic acid

-

-

-

-

Linezolid

2

4

22

19

Metronidazole

-

-

-

-

Mupirocin

-

-

-

-

Nitrofurantoin (uncomplicated UTI only)

-

-

-

-

0.06

0.5

22

17

Spectinomycin

-

-

-

-


-

-

-

-


1

2

18

15

Rifampicin


30

10

5

1.25-23.75

21

21


36


Viridans group streptococci In endocarditis, refer to national or international endocarditis guidelines for breakpoints for viridans group streptococci.

Penicillins

Disk diffusion (EUCAST standardised disk diffusion method) Medium: Mueller-Hinton agar + 5% defibrinated horse blood and 20 mg/L β-NAD (MH-F) Inoculum: McFarland 0.5 Incubation: 5% CO2, 35±1ºC, 18±2h Reading: Read zone edges as the point showing no growth viewed from the front of the platewith the lid removed and with reflected light. Quality control: Streptococcus pneumoniae ATCC 49619


R>


-

-



-

38


Viridans group streptococci Fluoroquinolones



Ciprofloxacin

-

-

-

-

Levofloxacin

-

-

-

-

NA -

NA -

NA -

NA -

Moxifloxacin Nalidixic acid (screen) Norfloxacin Ofloxacin

Aminoglycosides



Amikacin

-

-

-

-

Gentamicin

-

-

-

-


-

-

-

-

Glycopeptides


R>

Teicoplanin

21

2

Telavancin

IE

IE

Vancomycin

21

2


16A

16A

IE

IE

5

15A

15A


39


Viridans group streptococci Macrolides, lincosamides and streptogramins



Azithromycin

IE

IE

IE

IE

Clarithromycin

IE

IE

IE

IE

Erythromycin

IE

IE

IE

IE

Roxithromycin

IE

IE

IE

IE

Telithromycin

IE

IE

IE

IE

Clindamycin1

0.5

0.5

19A

19A


IE

IE

IE

IE

Tetracyclines


2


Doxycycline

-

-

-

-

Minocycline

-

-

-

-

Tetracycline Tigecycline

IE

IE

IE

IE




Chloramphenicol

-

-

-

-

Colistin

-

-

-

-

Daptomycin Fosfomycin iv

-

-

-

-


-

-

-

-

Fusidic acid

-

-

-

-

Linezolid Mupirocin

-

-

-

-


-

-

-

-

Rifampicin

-

-

-

-

Spectinomycin

-

-

-

-


-

-

-

-


-

-

-

-

Metronidazole

1/A. Inducible clindamycin resistance can be detected only in the presence of a macrolide antibiotic. In disk diffusion tests look for apparent antagonism of clindamycin by erythromycin (D-test).

40


Haemophilus influenzae

Disk diffusion (EUCAST standardised disk diffusion method) Medium: Mueller-Hinton agar + 5% defibrinated horse blood and 20 mg/L β-NAD (MH-F) Inoculum: McFarland 0.5 Incubation: 5% CO2, 35±1ºC, 18±2h Reading: Read zone edges as the point showing no growth viewed from the front of the plate with the lid removed and with reflected light. Quality control: Haemophilus influenzae NCTC 8468

Penicillins


R>


Doripenem1

12

1

10

20

20

Ertapenem1

0.52

0.5

10

20

20

22

2

10

20

20

22 0.25

2

10

20A

20A

NoteA

NoteA

Imipenem

Meropenem3 (infections other than meningitis) Meropenem3 (meningitis)

1



IE

IE


Ciprofloxacin

0.52

R>

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) S≥ R< IE

IE


Chloramphenicol

2

2

Colistin

-

-


IE

Fosfomycin-trometamol (uncomplicated UTI only) Fusidic acid

Zone diameter breakpoint (mm) S≥

R


Note IE

3

2-1

-

-

19

19

-1

-

-

Note3 IE

NoteA IE

NoteA IE


IE

IE

IE

IE


-

-

-

-

Oxacillin

-

-

-

-

Cloxacillin

-

-

-

-

Dicloxacillin

-

-

-

-

Flucloxacillin

-

-

-

-


-

-

-

-

1. Most M. catarrhalis produce beta-lactamase, although beta-lactamase production is slow and may give weak results with in vitro tests. Beta-lactamase producers should be reported resistant to penicillins and aminopenicillins without inhibitors. 2. For susceptibility testing purposes, the concentration of sulbactam is fixed at 4 mg/L. 3/A. Susceptibility can be inferred from amoxicillin-clavulanate. 4. For susceptibility testing purposes, the concentration of clavulanate is fixed at 2 mg/L.

46


Moraxella catarrhalis Cephalosporins



S≤

R>

0.121 -

0.121 -

-

-

Cefadroxil

-

-

Cefalexin

-

-

-

-

Cefazolin

-

-

-

-

Cefepime

4

4

30

20

20

Cefixime

0.5

1

5

21

18

1

2

5

20

17

Cefoxitin

NA

NA

NA

NA

Cefpodoxime

IP

IP

IP

IP

-

-

-

-

Ceftibuten

IE

IE

IE

IE

Ceftriaxone

1

2

30

24

21

Cefuroxime

4

8

30

21

18

0.12

4

30

50

21

Cefaclor

Cefotaxime

Ceftazidime

Cefuroxime axetil

Carbapenems


10


S≤

R>

Doripenem

11

1

10

30

30

Ertapenem

0.51

0.5

10

29

29

Imipenem

21

2

10

29

29

Meropenem

21

2

10

33

33

Monobactams

Aztreonam


R>

IE

IE

1. MIC breakpoints render all M. catarrhalis resistant to cefaclor.


Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) R< S≥ IE

IE

47


Moraxella catarrhalis Fluoroquinolones



S≤

R>

Ciprofloxacin

0.5

0.5

5

23

23

Levofloxacin

1

1

5

23

23

Moxifloxacin

0.5

0.5

5

23

23


NA

NA

30

23A

23A

-

-

5

25

25

Norfloxacin Ofloxacin

Aminoglycosides

-

-

0.5

0.5



S≤

R>

Amikacin

IE

IE

IE

IE

Gentamicin

IE

IE

IE

IE

Netilmicin

IE

IE

IE

IE

Tobramycin

IE

IE

IE

IE

Glycopeptides


R>

A. The nalidixic acid disk diffusion test can be used to screen for fluoroquinolone resistance. Isolates with zone diameters ≥23 mm can be reported susceptible to levofloxacin, ciprofloxacin, moxifloxacin and ofloxacin. Isolates with zone diameters

Azithromycin

0.251

0.51

NoteA

NoteA

Clarithromycin

0.251 0.25

0.51 0.5

15

NoteA 23

NoteA 20

0.51 0.25

11 0.5

15

NoteA 23

NoteA 20

Clindamycin

-

-

-

-


-

-

-

-

Erythromycin Roxithromycin Telithromycin

Tetracyclines


R>

Doxycycline

11

21

Minocycline Tetracycline

11 1

21 2

Tigecycline

IE

IE



R>

Colistin Daptomycin

21 -

21 -

Fosfomycin iv

IE


-

Fusidic acid Linezolid Metronidazole Mupirocin


30 30

NoteA

NoteA

25A 28

22A 25

IE

IE

30A -

IE

IE

IE

-

-

-

-

-

-

-

-

-

-

-


-

-

-

-

Rifampicin

-

-

-

-

Spectinomycin

-

-

-

-


-

-

-

-

0.5

1

18

15



Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (µg) R< S≥ 30A -

Chloramphenicol


30

1.25-23.75

1/A. Breakpoints relate to the topical use of chloramphenicol.


49


Neisseria gonorrhoeae Penicillins1

MIC breakpoint Notes Numbers for comments on MIC breakpoints (mg/L) Disk diffusion criteria for antimicrobial susceptibility testing of Neisseria gonorrhoeae have R > not yet been determined. S≤ 1. Always test for beta-lactamase. If positive, report resistant to benzylpenicillin, ampicillin and amoxicillin. The susceptibility of beta-lactamase negative isolates to ampicillin and amoxicillin can be inferred from the susceptibility to benzylpenicillin.

Benzylpenicillin

0.06

1

Ampicillin1 Ampicillin-sulbactam

Note1 IE

Note1 IE

Amoxicillin1 Amoxicillin-clavulanate

Note1

Note1

1

Note1

Note

Piperacillin

-

-


-

-

Ticarcillin

-

-


-

-


-

-

Oxacillin

-

-

Cloxacillin

-

-

Dicloxacillin

-

-

Flucloxacillin

-

-


-

-

50


Neisseria gonorrhoeae Cephalosporins

MIC breakpoint Notes Numbers for comments on MIC breakpoints (mg/L) Disk diffusion criteria for antimicrobial susceptibility testing of Neisseria gonorrhoeae have R > not yet been determined. S≤

Cefaclor

-

-

Cefadroxil

-

-

Cefalexin

-

-

Cefazolin

-

-

Cefepime Cefixime1

0.12

0.12

Cefotaxime

0.12

0.12

Cefoxitin Cefpodoxime

-

-

IE

IE

-

-

Ceftibuten

IE

IE

Ceftriaxone

0.12

0.12

Cefuroxime

-

-

Cefuroxime axetil

-

-

Ceftazidime

Carbapenems


Doripenem

IE

IE

Ertapenem

IE

IE

Imipenem

IE

IE

Meropenem

IE

IE

Monobactams

Aztreonam

1. Neisseria gonorrhoeae without resistance mechanisms to cefixime have MICs of ≤0.06 mg/L and can be treated with current standard dosing. The implications of alternative dosing schedules and recent data relating MIC to outcome are under consideration.

MIC breakpoint Notes Numbers for comments on MIC breakpoints (mg/L) Disk diffusion criteria for antimicrobial susceptibility testing of Neisseria gonorrhoeae have R > not yet been determined. S≤ IE

IE

51


Neisseria gonorrhoeae Fluoroquinolones1


Ciprofloxacin

0.03

0.06

Levofloxacin

IE

IE

Moxifloxacin

IE

IE


NA

NA


Aminoglycosides

IE

IE

0.12

0.25


Amikacin

-

-

Gentamicin

-

-

Netilmicin

-

-

Tobramycin

-

-

Glycopeptides


Teicoplanin

-

-

Telavancin

-

-

Vancomycin

-

-

52


Neisseria gonorrhoeae Macrolides, lincosamides and streptogramins

MIC breakpoint Notes Numbers for comments on MIC breakpoints (mg/L) Disk diffusion criteria for antimicrobial susceptibility testing of Neisseria gonorrhoeae have R > not yet been determined. S≤ 0.25

0.5

Clarithromycin

-

-

Erythromycin

-

-

Roxithromycin

-

-

Telithromycin

-

-

Clindamycin Quinupristin-dalfopristin

-

-

Azithromycin

Tetracyclines1

MIC breakpoint Notes Numbers for comments on MIC breakpoints (mg/L) Disk diffusion criteria for antimicrobial susceptibility testing of Neisseria gonorrhoeae have R > not yet been determined. S≤ 1. Isolates susceptible to tetracycline are also susceptible to minocycline, but some isolates resistant to tetracycline may be susceptible to minocycline.

Doxycycline

IE

IE

Minocycline

0.5

1

Tetracycline

0.5

1

Tigecycline

IE

IE



Chloramphenicol

-

-

Colistin

-

-


-

-


-

-

Fusidic acid

-

-

Linezolid

-

-

Metronidazole Mupirocin Nitrofurantoin (uncomplicated UTI only)

-

-

-

-

64

64


-

-


-

-

Rifampicin Spectinomycin

53


Neisseria meningitidis Penicillins

MIC breakpoint Notes Numbers for comments on MIC breakpoints (mg/L) Disk diffusion criteria for antimicrobial susceptibility testing of Neisseria meningitidis have R > not yet been determined. S≤

Benzylpenicillin

0.06

Ampicillin

0.12

1

IE

IE


0.25

0.12

1


-

-

Piperacillin

-

-


-

-

Ticarcillin

-

-


-

-


-

-

Oxacillin

-

-

Cloxacillin

-

-

Dicloxacillin

-

-

Flucloxacillin

-

-


-

-

Amoxicillin

54


Neisseria meningitidis Cephalosporins


Cefaclor

-

-

Cefadroxil

-

-

Cefalexin

-

-

Cefazolin

-

-

Cefepime Cefixime Cefotaxime

0.121

0.12

Cefpodoxime

-

-

Ceftazidime

-

-

Ceftibuten

-

-

Ceftriaxone

0.121 -

0.12

-

-


Cefoxitin

Cefuroxime Cefuroxime axetil

Carbapenems

-


Doripenem

IE

IE

Ertapenem

-

-

Imipenem

-

-

0.252

0.25

Meropenem1

Monobactams

Aztreonam

1. Isolates with MIC values above the susceptible breakpoint are very rare or not yet reported. The identification and antimicrobial susceptibility tests on any such isolate must be repeated and if the result is confirmed the isolate sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC values above the current resistant breakpoint they should be reported resistant. 2. Breakpoints relate to meningitis only.

MIC breakpoint Notes Numbers for comments on MIC breakpoints (mg/L) Disk diffusion criteria for antimicrobial susceptibility testing of Neisseria meningitidis have R > not yet been determined. S≤ -

-

55


Neisseria meningitidis Fluoroquinolones

Ciprofloxacin Levofloxacin

MIC breakpoint Notes Numbers for comments on MIC breakpoints (mg/L) Disk diffusion criteria for antimicrobial susceptibility testing of Neisseria meningitidis have R > not yet been determined. S≤ 0.031 IE

0.061 IE

Moxifloxacin

IE

IE


NA

NA

Norfloxacin

-

-

Ofloxacin

IE

IE

Aminoglycosides


Amikacin

-

-

Gentamicin

-

-


-

-

Glycopeptides

1. Breakpoints apply only to use in the prophylaxis of meningococcal disease.


Teicoplanin

-

-

Telavancin

-

-

Vancomycin

-

-

56


Neisseria meningitidis Macrolides, lincosamides and streptogramins


Azithromycin

-

-

Clarithromycin

-

-

Erythromycin

-

-

Roxithromycin

-

-

Telithromycin

-

-

Clindamycin Quinupristin-dalfopristin

-

-

Tetracyclines


Doxycycline

-

-

Minocycline1

1

2

Tetracycline

1

2

Tigecycline

IE

IE



Chloramphenicol

2

4

Colistin

-

-


-

-


-

-

Fusidic acid

-

-

Linezolid

-

-

Metronidazole Mupirocin Nitrofurantoin (uncomplicated UTI only)

-

-

0.25

0.25

-

-

-

-

Rifampicin1 Spectinomycin Trimethoprim (uncomplicated UTI only) Trimethoprim-sulfamethoxazole

1. Tetracycline can be used to predict susceptibility to minocycline for prophylaxis against N. meningitidis infections.

1. For prophylaxis of meningitis only (refer to national guidelines).

57


Gram-positive anaerobes except Clostridium difficile Penicillins

Benzylpenicillin1

MIC breakpoint Notes Numbers for comments on MIC breakpoints (mg/L) Disk diffusion criteria for antimicrobial susceptibility testing of anaerobes have not yet been R > determined. S≤ 0.25

0.5

1. Susceptibility to ampicillin, amoxicillin and piperacillin without beta-lactamase inhibitors can be inferred from susceptibility to benzylpenicillin.

Ampicillin

4

8


42 4

82 8

2. For susceptibility testing purposes, the concentration of sulbactam is fixed at 4 mg/L.

43 8

83 16

3. For susceptibility testing purposes, the concentration of clavulanate is fixed at 2 mg/L.

84 8

164 16

4. For susceptibility testing purposes, the concentration of tazobactam is fixed at 4 mg/L.

Ticarcillin Ticarcillin-clavulanate

83

163


IE

IE

Oxacillin

-

-

Cloxacillin

-

-

Dicloxacillin

-

-

Flucloxacillin

-

-


-

-

Amoxicillin Amoxicillin-clavulanate Piperacillin Piperacillin-tazobactam

Cephalosporins

MIC breakpoint Notes Numbers for comments on MIC breakpoints (mg/L) Disk diffusion criteria for antimicrobial susceptibility testing of anaerobes have not yet been R > determined. S≤

Cefaclor

-

-

Cefadroxil

-

-

Cefalexin

-

-

Cefazolin

-

-

Cefepime

-

-

Cefixime

-

-

Cefotaxime

-

-

Cefpodoxime

-

-

Ceftazidime

-

-

Ceftibuten

-

-

Ceftriaxone

-

-

Cefuroxime

-

-

Cefuroxime axetil

-

-

Cefoxitin

58


Gram-positive anaerobes except Clostridium difficile Carbapenems


Doripenem

1

1

Ertapenem

1

1

Imipenem

2

8

Meropenem

2

8

Monobactams

Aztreonam

Fluoroquinolones

MIC breakpoint Notes Numbers for comments on MIC breakpoints (mg/L) Disk diffusion criteria for antimicrobial susceptibility testing of anaerobes have not yet been R > determined. S≤ -

-


Ciprofloxacin

-

Levofloxacin

-

-

Moxifloxacin

IE

IE


NA

NA

-

-


-

59


Gram-positive anaerobes except Clostridium difficile Aminoglycosides


Amikacin

-

-

Gentamicin

-

-


-

-

Glycopeptides


Teicoplanin

IE

IE

Telavancin

IE

IE

Vancomycin

2

2



Azithromycin

-

Clarithromycin

-

-

Erythromycin

IE

IE

Roxithromycin

-

-

Telithromycin

-

-

Clindamycin

4

4

Quinupristin/dalfopristin

-

-

60


Gram-positive anaerobes except Clostridium difficile Tetracyclines1

MIC breakpoint Notes Numbers for comments on MIC breakpoints (mg/L) Disk diffusion criteria for antimicrobial susceptibility testing of anaerobes have not yet been R > determined. S≤ 1. For anaerobic bacteria there is clinical evidence of activity in mixed intra-abdominal infections, but no correlation between MIC values, Pk/Pd data and clinical outcome. Therefore no breakpoints for susceptibility testing are given.

Doxycycline Minocycline

Note1 Note1

Note1 Note1

Tetracycline Tigecycline

Note1 Note1

Note1 Note1



Chloramphenicol

8

8

Colistin

-

-

Daptomycin

-

-

Fosfomycin iv

-

-


-

-

Fusidic acid

-

-

Linezolid

-

-

Metronidazole

4

4

Mupirocin

-

-


-

-

Rifampicin

-

-

Spectinomycin

-

-


-

-


-

-

61


Clostridium difficile Antibiotic agent

MIC breakpoint Notes Numbers for comments on MIC breakpoints (mg/L) Disk diffusion criteria for antimicrobial susceptibility testing of Clostridium difficile have not R > yet been determined. S≤

Daptomycin

-1

-1

1. Not used clinically. May be tested for epidemiological purposes only (ECOFF: WT ≤ 4 mg/L).

Fusidic acid

-2

-2

2. Not used clinically. May be tested for epidemiological purposes only (ECOFF: WT ≤ 2 mg/L).

Metronidazole

23

23

Moxifloxacin

-4

-4

3. The breakpoints are based on epidemiological cut-off values (ECOFFs), which distinguish wild-type isolates from those with reduced susceptibility. 4. Not used clinically. May be tested for epidemiological purposes only (ECOFF: WT ≤ 4 mg/L).

Tigecycline

-5

-5

5. Not used clinically. May be tested for epidemiological purposes only (ECOFF: WT ≤ 0.25 mg/L).

Rifampicin

-

6

-6

6. Not used clinically. May be tested for epidemiological purposes only (ECOFF: WT ≤ 0.004 mg/L).

Vancomycin

23

23

62


Gram-negative anaerobes Penicillins


Benzylpenicillin1

0.25

Ampicillin1

0.5

2


42 0.5

82 2

2. For susceptibility testing purposes, the concentration of sulbactam is fixed at 4 mg/L.

43 16

83 16

3. For susceptibility testing purposes, the concentration of clavulanate is fixed at 2 mg/L.

84 16

164 16

4. For susceptibility testing purposes, the concentration of tazobactam is fixed at 4 mg/L.

Ticarcillin1 Ticarcillin-clavulanate1

83

163


IE

IE

Oxacillin

-

-

Cloxacillin

-

-

Dicloxacillin

-

-

Flucloxacillin

-

-


-

-

Amoxicillin1 Amoxicillin-clavulanate1 Piperacillin

1

Piperacillin-tazobactam1

Cephalosporins

0.5


Cefaclor

-

-

Cefadroxil

-

-

Cefalexin

-

-

Cefazolin

-

-

Cefepime

-

-

Cefixime

-

-

Cefotaxime

-

-

NA

NA

Cefpodoxime

-

-

Ceftazidime

-

-

Ceftibuten

-

-

Ceftriaxone

-

-

Cefuroxime

-

-

Cefuroxime axetil

-

-

Cefoxitin

1. Susceptibility to ampicillin, amoxicillin and piperacillin without beta-lactamase inhibitors can be inferred from susceptibility to benzylpenicillin.

63


Gram-negative anaerobes Carbapenems


Doripenem

1

1

Ertapenem

1

1

Imipenem

2

8

Meropenem

2

8

Monobactams

Aztreonam

Fluoroquinolones


-


Ciprofloxacin

-

Levofloxacin

-

-

Moxifloxacin

IE

IE


NA

NA

Norfloxacin

-

-

Ofloxacin

-

-

64


Gram-negative anaerobes Aminoglycosides


Amikacin

-

-

Gentamicin

-

-

Netilmicin

-

-

Tobramycin

-

-

Glycopeptides

Teicoplanin


Telavancin

-

-

Vancomycin

-

-



Azithromycin

-

Clarithromycin

-

-

Erythromycin

IE

IE

Roxithromycin Telithromycin

-

-

Clindamycin

4

4


-

-

65


Gram-negative anaerobes Tetracyclines1

MIC breakpoint Notes Numbers for comments on MIC breakpoints (mg/L) Disk diffusion criteria for antimicrobial susceptibility testing of anaerobes have not yet been R > determined. S≤ 1. For anaerobic bacteria there is clinical evidence of activity in mixed intra-abdominal infections, but no correlation between MIC values, Pk/Pd data and clinical outcome. Therefore no breakpoints for susceptibility testing are given.

Doxycycline

Note1

Note1

Minocycline

Note

1

Note1

Tetracycline

Note1

Note1

1

Note1

Tigecycline


Note


Chloramphenicol

8

8

Colistin

-

-

Daptomycin

-

-

Fosfomycin iv

-

-


-

-

Fusidic acid

-

-

Linezolid

-

-

Metronidazole

4

4

Mupirocin

-

-


-

-

Rifampicin

-

-

Spectinomycin

-

-


-

-


-

-

66


Helicobacter pylori Antibiotic agent

MIC breakpoint Notes Numbers for comments on MIC breakpoints (mg/L) R> S≤ 1. The breakpoints are based on epidemiological cut-off values (ECOFFs), which distinguish wild-type isolates from those with reduced susceptibility.

Amoxicillin Clarithromycin

0.121 0.25

1

0.121 0.51

Levofloxacin

11

11

Metronidazole

81

81

Rifampicin

11

11

Tetracycline

11

11

67


Listeria monocytogenes

Disk diffusion (EUCAST standardised disk diffusion method ) Medium: Mueller-Hinton agar + 5% defibrinated horse blood and 20 mg/L β-NAD (MH-F) Inoculum: McFarland 0.5 Incubation: 5% CO2, 35±1ºC, 18±2h Reading: Read zone edges as the point showing no growth viewed from the front of the plate with the lid removed and with reflected light. Quality control: Streptococcus pneumoniae ATCC 49619

Antibiotic agent

MIC breakpoint (mg/L) R> S≤

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints (µg) R < Letters for comments on disk diffusion S≥

Ampicillin

1

1

2

16

16

Benzylpenicillin

1

1

1 unit

13

13

Erythromycin

1

1

15

25

25

Meropenem

0.25

0.25

10


0.06

0.06

1.25-23.75

26 29

26 29


68


Non-species related breakpoints Penicillins

MIC breakpoint Non-species related breakpoints are based on the following dosages (mg/L) (See section 8 in Rationale Documents) R> S≤ 0.25

2

Ampicillin

2

8

The non-species related S/I and I/R breakpoints are based on 600 mg x 4 (2.4 g/day) and 2.4 g x 6 (14.4 g/day) doses respectively. The non-species related breakpoints are based on doses of at least 0.5 g x 3-4 (1.5-2 g/day).


2

8

Rationale document in preparation.

Amoxicillin

2

8

The non-species related breakpoints are based on doses of at least 0.5 g x 3-4 (1.5-2 g/day).


2

8


Piperacillin

4

16

Breakpoints apply to piperacillin-tazobactam dosage of 4 g x 3.


4

16

Breakpoints apply to piperacillin-tazobactam dosage of 4 g x 3.

Ticarcillin

8

16


8

16


IE

IE

Oxacillin

IE

IE

Cloxacillin

IE

IE

Dicloxacillin

IE

IE

Flucloxacillin

IE

IE

Mecillinam

IE

IE

Benzylpenicillin

Cephalosporins

MIC breakpoint Non-species related breakpoints are based on the following dosages (mg/L) (See section 8 in Rationale Documents) S≤ R>

Cefaclor

IE

IE

Cefadroxil

IE

IE

Cefalexin

IE

IE

Cefazolin

1

2


Cefepime

4

8

Breakpoints apply to a daily intravenous dose of 2 g x 2 and a high dose of at least 2 g x 3.

Cefixime

IE

IE

Cefotaxime

1

2

Cefoxitin

IE

IE


Cefpodoxime

IE

IE

Ceftazidime

4

8

Ceftibuten

IE

IE

Ceftriaxone

1

2


Cefuroxime

4

8

Breakpoints apply to a daily intravenous dose of 750 mg x 3 and a high dose of at least 1.5 g x 3.

Cefuroxime axetil

IE

IE


69


Non-species related breakpoints Carbapenems

MIC breakpoint Non-species related breakpoints are based on the following dosages (mg/L) (See section 8 in Rationale Documents) R> S≤

Doripenem

1

4

EUCAST breakpoints apply to doripenem 500 mg x 3 daily administered intravenously over 1 hour as the lowest dose. 500 mg x 3 daily administered over 4 hours was taken into consideration for severe infections and in setting the I/R breakpoint.

Ertapenem

0.5

1

Imipenem

2

8

Meropenem

2

8

EUCAST breakpoints apply to ertapenem 1000 mg x 1 daily administered intravenously over 30 minutes as the only dose. EUCAST breakpoints apply to imipenem 500 mg x 4 daily administered intravenously over 30 minutes as the lowest dose. 1 g x 4 daily was taken into consideration for severe infections and in setting the I/R breakpoint. EUCAST breakpoints apply to meropenem 1000 mg x 3 daily administered intravenously over 30 minutes as the lowest dose. 2 g x 3 daily was taken into consideration for severe infections and in setting the I/R breakpoint.

Monobactams

Aztreonam

Fluoroquinolones

MIC breakpoint Non-species related breakpoints are based on the following dosages (mg/L) (See section 8 in Rationale Documents) R> S≤ 4

8


MIC breakpoint Non-species related breakpoints are based on the following dosages (mg/L) (See section 8 in Rationale Documents) R> S≤

Ciprofloxacin

0.5

1

Breakpoints apply to an oral dose of 500 mg x 2 (or as low as 250 mg x 2 for uncomplicated urinary tract infections) to 750 mg x 2 and an intravenous dose of 400 mg x 2 to 400 mg x 3. Breakpoints apply to an oral dose of 500 mg x 1 to 500 mg x 2 and an intravenous dose of 500 mg x 1 to 500 mg x 2. Breakpoints apply to an oral and iv dose of 400 mg x 1.

Levofloxacin

1

2

Moxifloxacin

0.5

1

Nalidixic acid

IE

IE

Norfloxacin

0.5

1

Breakpoints apply to an oral dose of 400 mg x 2.

Ofloxacin

0.5

1

Breakpoints apply to an oral dose of 200 mg x 2 to 400 mg x 2 and an intravenous dose of 200 mg x 2 to 400 mg x 2.

70


Non-species related breakpoints Aminoglycosides


Amikacin

8

16

Gentamicin

2

4

Netilmicin

2

4

Tobramycin

2

4

Glycopeptides


Teicoplanin

IE

IE

Telavancin

IE

IE

Vancomycin

IE

IE


EUCAST breakpoints apply to intravenous amikacin dosage of 15 mg/kg/day. In the absence of Pk/Pd data these have been determined mainly on the basis of Pk data and pre-existing breakpoints. Breakpoints apply to intravenous gentamicin dosage of 3-4.5 mg/kg/day. In the absence of Pk/Pd data these have been determined mainly on the basis of Pk data and pre-existing breakpoints. Breakpoints apply to intravenous netilmicin dosage of 4-6 mg/kg/day. In the absence of Pk/Pd data these have been determined mainly on the basis of Pk data and pre-existing breakpoints. EUCAST breakpoints apply to intravenous tobramycin dosage of 3-4.5 mg/kg/day. In the absence of Pk/Pd data these have been determined mainly on the basis of Pk data and pre-existing breakpoints.


Azithromycin

IE

IE

Clarithromycin

IE

IE

Erythromycin

IE

IE

Roxithromycin

IE

IE

Telithromycin

IE

IE

Clindamycin

IE

IE


IE

IE

71


Non-species related breakpoints Tetracyclines


Doxycycline

IE

IE

Minocycline

IE

IE

Tetracycline

IE

IE

Tigecycline

0.25

0.5

Miscellaneous

Breakpoints apply to a tigecycline intravenous dose of 100 mg followed by 50 mg 12 hourly for CSSSI and CIAI.


Chloramphenicol

IE

IE

Colistin

IE

IE

Daptomycin

IE

IE

Fosfomycin iv

IE

IE

Fosfomycin-trometamol

IE

IE

Fusidic acid

IE

IE

Linezolid

2

4

Metronidazole

IE

IE

Mupirocin

IE

IE

Nitrofurantoin

IE

IE

Rifampicin

IE

IE

Spectinomycin

IE

IE

Trimethoprim

IE

IE


IE

IE

Breakpoints apply to a linezolid intravenous and oral dosage of 600 mg x 2.

72