European Committee On Antimicrobial Susceptibility Testing

European Committee on Antimicrobial Susceptibility Testing
Breakpoint tables for interpretation of MICs and zone diameters

Version 1.1 April 2010
Content
Notes Errata list Enterobacteriaceae Pseudomonas spp. Acinetobacter spp. Staphylococcus spp. Enterococcus spp. Streptococcus Groups A, B, C and G Streptococcus pneumoniae Other streptococci Hemophilus influenzae Moraxella catarrhalis Neisseria gonorrhoeae Neisseria meningitidis Gram-positive anaerobes Gram-negative anaerobes Non-species related breakpoints
Page
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Version 1.1, April 2010
Notes
1. The EUCAST tables of clinical breakpoints contain clinical MIC breakpoints (determined over the period 2002-2010) and their inhibition zone diameter correlates. The latter are tentative for the period December 2009 - November 2010. In April 2010 a version 1.1 is published where typographical errors have been corrected, MIC breakpoints for some antibiotics have been revised, a few correlates between MIC and inhibition zones have been updated and a few new zone diameter breakpoints have been added. Changes are indicated by shaded cells. 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 disk diffusion test breakpoints. 4. Highlighted antimicrobial names link to EUCAST rationale documents. Highlighted MIC breakpoints and disk diffusion 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 disk diffusion test breakpoint of "S 50 mm" is an arbitrary "off scale" zone diameter breakpoint corresponding to MIC breakpoint situations where wild type isolates are categorized as intermediate (i.e. no fully susceptible isolates exist).
Abbreviations and definitions

"-" 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-categorization may be reported. NA = Not Applicable IP = In Preparation
2

Version 1.1, April 2010
Version number
Version 1.1 2010-04-27
Group of organisms
All
Changes
S > corrected to S and S < corrected to S at several positions. All comments referring to "adjusting MIC breakpoints to avoid dividing wild type MIC distributions" have been removed. A list can be obtained from EUCAST. Note on zone diameter breakpoints for ampicillin corrected (14/14 and 50/14 instead of 12/12 and 50/12). New comments on mecillinam and nitrofurantoin, cephalosporins, carbapenems and aztreonam. New MIC and zone diameter breakpoints for cefepime, ceftazidime and aztreonam. New MIC breakpoints for colistin. Zone diameter breakpoints for S. maltophilia and trimethoprim-sulfamethoxazole added. New comment on penicillins. Zone diameter breakpoints for S. saprophyticus and ampicillin. Cefpoxitin corrected to cefoxitin for coagulase-negative staphylococci. New comment on nitrofurantoin. Zone diameter breakpoints for E. faecium and quinupristin-dalfopristin added. MIC breakpoints for carbapenems removed. Susceptibility is inferred from the penicillin susecptibility. Zone diameter breakpoints for norfloxacin added (screen disk for fluoroquinolone resistance). New comment on nitrofurantoin. Zone diameter breakpoints for oxacillin changed from 18/18 to 20/20.
Enterobacteriaceae
Pseudomonas spp. Staphylococcus spp.
Enterococcus spp. Streptococcus A, B, C and G
Stretococcus pneumoniae
Enterobacteriaceae
Penicillins1 MIC breakpoint (mg/L) S R>
EUCAST Clinical Breakpoint Table v. 1.1 2010-04-27

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (g) R< S
1. For aminopenicillin breakpoints, the resistant breakpoint of >8 mg/L ensures that all isolates with resistance mechanisms are reported resistant. The wide range of dosages and intravenous versus oral administration significantly affect therapeutic efficacy. The unspecified susceptible breakpoint enables the user to categorize wild type E. coli and P. mirabilis as either susceptible or intermediate to the aminopenicillins depending on dosing, route of administration and whether the infection is systemic or affects the urinary tract only.
Benzylpenicillin Ampicillin
Note1
10 NoteA
14
A. Different dosing and reporting practices in different countries mean that wild type (without resistance mechanisms) Enterobacteriaceae may be categorized as either susceptible or intermediate to aminopenicillins. If it is common practice to categorize wild type Enterobacteriaceae as susceptible, use breakpoints of S 14mm, R <14 mm; to categorize the wild type as intermediate use S 50 mm, R <14 mm. 2. For susceptibility testing purposes, the concentration of sulbactam is fixed at 4 mg/L. B. Susceptibility inferred from ampicillin. 3. For susceptibility testing purposes, the concentration of clavulanate is fixed at 2 mg/L. 4. For susceptibility testing purposes, the concentration of clavulanate is fixed at 4 mg/L.
Ampicillin-sulbactam2 Amoxicillin Amoxicillin-clavulanate3 Piperacillin Piperacillin-tazobactam4 Ticarcillin Ticarcillin-clavulanate3 Phenoxymethylpenicillin Mecillinam (uncomplicated UTI only) 5
Note1 Note1 Note1 8 8 8 8 8
8 8 8 16 16 16 16 8
10-10 20-10 30 30-6 75 75-10
IP NoteB NoteA 18 18 23 23 -
IP NoteB 12 15 15 22 22 15
10
15
5. Mecillinam (pivmecillinam) breakpoints relate to E. coli, Klebsiella spp. and P. mirabilis only.
Cephalosporins1
MIC breakpoint (mg/L) S R>
1. The cephalosporin breakpoints for Enterobacteriaceae will detect all clinically important resistance mechanisms (including ESBL, plasmid mediated AmpC). Some strains that produce beta-lactamases are susceptible or intermediate to 3rd or 4th generation cephalosporins with these breakpoints and should be reported as found, i.e. the presence or absence of an ESBL does not in itself influence the categorization of susceptibility. In many areas, ESBL detection and characterization is recommended or mandatory for infection control purposes.
Cefaclor Cefadroxil (uncomplicated UTI only) Cefalexin (uncomplicated UTI only) Cefazolin Cefepime Cefixime (uncomplicated UTI only) Cefotaxime Cefoxitin Cefpodoxime (uncomplicated UTI only) Ceftazidime Ceftibuten (uncomplicated UTI only) Ceftriaxone Cefuroxime Cefuroxime axetil (uncomplicated UTI only)
16 16 1 1 1 NA 1 1 1 1 82 8
16 16 4 1 2 NA 1 4 1 2 8 8
30 30 30 5 5 10 10 30 30 30 30
12 IP 24 17 21 NA 21 21 21 23 18 18
12 IP 21 17 18 NA 21 18 21 20 18 18
2. The breakpoint relates to a dosage of 1.5 g x 3 and to E. coli, P. mirabilis and Klebsiella spp. only.
Enterobacteriaceae
Carbapenems1 MIC breakpoint (mg/L) S R>

1. The carbapenem breakpoints for Enterobacteriaceae will detect all clinically important resistance mechanisms (including the majority of carbapenemases). Some strains that produce carbapenemase are categorized 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 categorization of susceptibility. In many areas, carbapenemase detection and characterization is recommended or mandatory for infection control purposes.
Doripenem Ertapenem Imipenem2 Meropenem
1 0.5 2 2
4 1 8 8
10 10 10 10
24 25 21 22
18 22 15 16
2. Proteus and Morganella species are considered poor targets for imipenem.
Monobactams

4
30 27 24 1. The aztreonam breakpoints for Enterobacteriaceae will detect clinically important resistance mechanisms (including ESBL). Some strains that produce beta-lactamases are susceptible or intermediate to 3rd or 4th generation cephalosporins with these breakpoints and should be reported as found, i.e. the presence or absence of an ESBL does not in itself influence the categorization of susceptibility. In many areas, ESBL detection and characterization is recommended or mandatory for infection control purposes.
Aztreonam1
Fluoroquinolones

1
5 22 19 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>0.064 mg/L). The available data relate mainly to S. typhi but there are also case reports of poor response with other Salmonella species.
Ciprofloxacin1
0.5
Levofloxacin Moxifloxacin Nalidixic acid (screen)
1 0.5 Note2
2 1 Note2
5 5 30
22 20 16A
19 17 16A 2/A. Nalidixic acid may be used to screen for fluoroquinolone resistance in Enterobacteriaceae. The zone diameter breakpoint correlates with an MIC value of 16 mg/L in most Enterobacteriaceae. If Salmonella spp. are resistant report resistant to all fluoroquinolones. If other Enterobacteriaceae are resistant, then test the agent in question.
Norfloxacin Ofloxacin
0.5 0.5
1 1
10 5
22 22
19 19
Enterobacteriaceae
Aminoglycosides1 MIC breakpoint (mg/L) S
Amikacin Gentamicin Netilmicin Tobramycin 8 2 2 2

1. Aminoglycoside breakpoints are based on once-daily administration of high aminoglycoside dosages. Most often aminoglycosides are given in combination with beta-lactam agents. 16 4 4 4 30 10 10 10 16 17 15 15 13 14 12 12
R>
Macrolides, lincosamides and streptogramins

-
1. Azithromycin has been used in the treatment of infections with Salmonella typhi (MIC 16 mg/L for wild type isolates) and Shigella spp.
Azithromycin1
Tetracyclines

2
18 15
Doxycycline Minocycline Tetracycline Tigecycline1
15
1. Tigecycline has decreased activity against Morganella spp., Proteus spp. and Providencia spp.
Miscellaneous agents

8 2 32 32 64 4 4
30 17 NoteA 11 18 16 17 NoteA 11 15 13 A. Test by MIC method only.
Chloramphenicol Colistin Daptomycin Fosfomycin iv Fosfomycin-trometamol (uncomplicated UTI only) Fusidic acid Linezolid Metronidazole Nitrofurantoin (uncomplicated UTI only)1 Rifampicin Spectinomycin Trimethoprim (uncomplicated UTI only) Trimethoprim-sulfamethoxazole (co-trimoxazole) 2
8 2 32 32 64 2 2
100
1. Breakpoints relate to E. coli only.
5 1.25-23.75
2. Trimethoprim:sulfamethoxazole in the ratio 1:19. Breakpoints are expressed as the trimethoprim concentration.
Pseudomonas spp.
Penicillins MIC breakpoint (mg/L)

Disk Zone diameter Notes content breakpoint (mm) Numbers for comments on MIC breakpoints Letters for comments on disk diffusion (g) S
30 30-6 75 75-10 19 19 IP IP -
S
Benzylpenicillin Ampicillin Ampicillin-sulbactam Amoxicillin Amoxicillin-clavulanate Piperacillin Piperacillin-tazobactam1,2 Ticarcillin3 Ticarcillin-clavulanate2, 3 Phenoxymethylpenicillin
1
R>
16 16 16 16 -
R<
19 19 IP IP 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).
16 16 16 16 -
Cephalosporins

8 NA 8 -
30 18 NA 10 16 18 NA 16 1. The breakpoints relate to high dose therapy (2 g x 3).
Cefaclor Cefadroxil Cefalexin Cefazolin Cefepime Cefixime Cefotaxime Cefoxitin Cefpodoxime Ceftazidime Ceftibuten Ceftriaxone Cefuroxime Cefuroxime axetil
81 NA 81 -
Pseudomonas spp.
Carbapenems MIC breakpoint (mg/L) S
Doripenem Ertapenem Imipenem Meropenem 1 4 2
1

10 10 10 22 20 24 17 17 18 1. The breakpoints relate to high dose, frequent therapy (1 g x 4).
R>
4 8 8
Monobactams

161
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.
Aztreonam
Fluoroquinolones

1 2 NA -
5 5 25 20 NA 22 17 NA -
Ciprofloxacin Levofloxacin Moxifloxacin Nalidixic acid Norfloxacin Ofloxacin
0.5 1 NA -
Aminoglycosides1
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 Gentamicin Netilmicin Tobramycin
8 4 4 4
16 4 4 4
30 10 10 10
18 15 10 15
15 15 10 15
Pseudomonas spp.
Miscellaneous MIC breakpoint (mg/L) S
Chloramphenicol Colistin Daptomycin Fosfomycin iv1 Fosfomycin-trometamol (uncomplicated UTI only) Fusidic acid Linezolid Metronidazole Nitrofurantoin (uncomplicated UTI only) Rifampicin Spectinomycin Trimethoprim (uncomplicated UTI only) Trimethoprim-sulfamethoxazole (co-trimoxazole)
2
R>
4 32 4
3
Note A
4 32 4
3
NoteA NoteA B
A. Test by MIC method only. 1. Intravenous fosfomycin may be used in combination with other drugs to treat P. aeruginosa infections.
NoteA 1.25-23.75 16
16B
2. Trimethoprim:sulfamethoxazole in the ratio 1:19. Breakpoints are expressed as the trimethoprim concentration. 3/B. S. maltophilia only.
Acinetobacter spp.
Penicillins1 MIC breakpoint (mg/L) S
Benzylpenicillin Ampicillin Ampicillin-sulbactam Amoxicillin Amoxicillin-clavulanate Piperacillin Piperacillin-tazobactam Ticarcillin Ticarcillin-clavulanate Phenoxymethylpenicillin IE IE IE IE IE -

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

4 8 8
10 10 10 21 23 21 15 17 15
Doripenem Ertapenem Imipenem Meropenem
1 2 2
Monobactams

-
-
Aztreonam
10
Acinetobacter spp.
Fluoroquinolones MIC breakpoint (mg/L) S
Ciprofloxacin Levofloxacin Moxifloxacin Nalidixic acid (screen) Norfloxacin Ofloxacin 1 1 NA -

5 5 30 21 21 IP 21 21 IP -
R>
1 2 NA -
Aminoglycosides1

16 4 4 4
1. Aminoglycoside breakpoints are based on once-daily administration of high aminoglycoside dosages. Most often aminoglycosides are given in combination with beta-lactam agents. 30 10 10 10 18 15 15 15 15 15 15 15
8 4 4 4
Tetracyclines

IE IE
IE IE IE IE
Doxycycline Minocycline Tetracycline Tigecycline
IE IE
11
Acinetobacter spp.
Chloramphenicol Colistin Daptomycin Fosfomycin iv Fosfomycin-trometamol (uncomplicated UTI only) Fusidic acid Linezolid Metronidazole Nitrofurantoin (uncomplicated UTI only) Rifampicin Spectinomycin Trimethoprim (uncomplicated UTI only) Trimethoprim-sulfamethoxazole (co-trimoxazole) 1 2 2

Note 1.25-23.75 16
A
R>
2 4
NoteA 13 1. Trimethoprim:sulfamethoxazole in the ratio 1:19. Breakpoints are expressed as the trimethoprim concentration. A. Test by MIC method only.
12
Staphylococcus spp.

1/A. Most staphylococci are penicillinase-producers. The benzylpenicillin breakpoint will mostly, but not unequivocally, separate beta-lactamase producers from non-producers. Isolates positive for betalactamase are resistant to benzylpenicillin, phenoxymethylpenicillin, amino-, carboxy- and ureidopenicillins. Isolates negative for beta-lactamase and susceptible to methicillin (oxacillin/cefoxitin susceptible) can be reported susceptible to these drugs. Isolates positive for beta-lactamase and susceptible to methicillin are susceptible to penicillin-beta-lactamase inhibitor combinations and penicillinase-resistant penicillins (oxacillin, cloxacillin, dicloxacillin and flucloxacillin). Isolates resistant to methicillin are resistant to all currently available beta-lactam agents, including beta-lactamase inhibitor combinations.
Benzylpenicillin Ampicillin Ampicillin-sulbactam Amoxicillin Amoxicillin-clavulanate Piperacillin Piperacillin-tazobactam Ticarcillin Ticarcillin-clavulanate Phenoxymethylpenicillin Oxacillin2 Cloxacillin Dicloxacillin Flucloxacillin Mecillinam (uncomplicated UTI only)
0.121 Note1 Note1 Note1 Note1 Note1 Note1 Note1 Note1 Note1 Note1,2 Note1 Note1 Note1 -
0.121,2 Note1 Note1 Note1 Note1 Note1 Note1 Note1 Note1 Note1 Note1,2 Note1 Note1 Note1 -
1 unit 2
26A 15A,B NoteA NoteA NoteA NoteA NoteA NoteA NoteA NoteA NoteA NoteA NoteA NoteA -
26A 15A,B NoteA NoteA NoteA NoteA NoteA NoteA NoteA NoteA NoteA NoteA NoteA NoteA -
B. Breakpoints relate to S. saprophyticus only.
2. S. aureus and S. lugdunensis with oxacillin MIC values >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.
13
Staphylococcus spp.
Cephalosporins1 MIC breakpoint (mg/L) S R>

1. Susceptibility of staphylococci to cephalosporins is inferred from the methicillin 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.
Cefaclor2 Cefadroxil Cefalexin Cefazolin Cefepime Cefixime Cefotaxime Cefoxitin (screen) S. aureus, S. lugdunensis
Note1 Note1 Note1 Note1 Note1 Note1 Note3
Note1 Note1 Note1 Note1 Note1 Note1 Note3 30
NoteA NoteA NoteA NoteA NoteA NoteA 22A
NoteA NoteA NoteA NoteA NoteA NoteA 22A
3. S. aureus and S. lugdunensis with cefoxitin MIC values >4 mg/L are mostly methicillin resistant due to the presence of the mecA gene whereas MIC for coagulase-negative staphylococi other than S. lugdunensis is a poorer predictor of methicillin resistance than the disk diffusion test.
Cefoxitin (screen) Coagulase-negative staphylococci Cefpodoxime Ceftazidime Ceftibuten Ceftriaxone Cefuroxime Cefuroxime axetil
Note3 Note IE
1
Note3 Note IE
1
30
25A Note IE
A
25A NoteA IE NoteA NoteA NoteA
Note1 Note1 Note1
Note1 Note1 Note1
NoteA NoteA NoteA
Carbapenems1

Note1 Note1 Note1 Note1
1/A. Susceptibility of staphylococci to carbapenems is inferred from the cefoxitin susceptibility. NoteA NoteA NoteA NoteA NoteA NoteA NoteA NoteA
14
Staphylococcus spp.
Fluoroquinolones1 MIC breakpoint (mg/L) S
Ciprofloxacin2 Levofloxacin Moxifloxacin Nalidixic acid Norfloxacin (screen) 1 1 0.5 NA NA

5 5 5 10 19 IP 22 NA 17A 19 IP 19 NA 17A A. Screen for fluoroquinolone resistance. Isolates categorized as susceptible can be reported susceptible to ciprofloxacin, levofloxacin, moxifloxacin and ofloxacin. Isolates categorized as resistant should be tested for susceptibility to individual agents. 1. For breakpoints for other fluoroquinolones (eg. pefloxacin and enoxacin) - refer to breakpoints determined by national breakpoint committees. 2. Breakpoints relate to high dose therapy.
R>
1 2 1 NA NA
Ofloxacin2
IP
IP
Aminoglycosides1

16 1 1 1
30 10 10 10 18 18 IP 19 15 18 IP 19 1. Aminoglycoside breakpoints are based on once-daily administration of high aminoglycoside dosages. Most often aminoglycosides are given in combination with beta-lactam agents. 2. Resistance to amikacin is most reliably determined by testing with kanamycin (zone diameter breakpoints under development).
Amikacin2 Gentamicin Netilmicin Tobramycin
8 1 1 1
Glycopeptides

21
NoteA NoteA 1. 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 I/R 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. Glycopeptide MICs are method dependent and should be determined by broth microdilution (reference ISO 20776 ). A. Disk diffusion is unreliable and cannot distinguish between wild type organisms and those with non-vanA -mediated resistance.
Teicoplanin, S. aureus, S.lugdunensis
21
Teicoplanin, Coagulase-negative staphylococci Vancomycin1
41 21
41 21
NoteA NoteA
NoteA NoteA
15
Staphylococcus spp.
Macrolides1, lincosamides and streptogramins MIC breakpoint (mg/L) S
Azithromycin1 Clarithromycin1 Erythromycin Roxithromycin Telithromycin Clindamycin2 Quinupristin-dalfopristin
1

1/A. Erythromycin can be used to determine susceptibility to azithromycin, clarithromycin and roxithromycin. 1 1 1 1 IE 0.25 1 2 2 2 2 IE 0.5 2 2 15 15 NoteA NoteA 21 NoteA IE 21B NoteC NoteA NoteA 18 NoteA IE 18B NoteC 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. Test by MIC method. Zone diameter breakpoints under development.
R>
Tetracyclines1

2 1 2 0.5
NoteA 30 30 15 IPA 22 18 NoteA IPA 19 18 1/A. Staphylococci susceptible to tetracycline are also susceptible to doxycycline and minocycline. Some staphylococci resistant to tetracycline may be susceptible to minocycline and/or doxycycline.

1
1 0.5 1 0.52
2. Strains with MIC values above the S/I 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 must be sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC above the current resistant breakpoint they should be reported resistant.
16
Staphylococcus spp.
Chloramphenicol Colistin Daptomycin 8 1

30 18 Note
A
R>
8 1
1
18 NoteA 1. Strains 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 must be sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC above the current resistant breakpoint they should be reported resistant. A. Test by MIC method only.
Fosfomycin iv Fosfomycin-trometamol (uncomplicated UTI only) Fusidic acid Linezolid Metronidazole Nitrofurantoin (uncomplicated UTI only)2 Rifampicin Spectinomycin Trimethoprim (uncomplicated UTI only) Trimethoprim-sulfamethoxazole (co-trimoxazole) 3
32 1 4 64 0.06 2 2
32 1 4 64 0.5 4 4 5 1.25-23.75 10 10 100 5
NoteA 22 17 13 25 17 17
NoteA 22 17 13 22 14 14 3. Trimethoprim:sulfamethoxazole in the ratio 1:19. Breakpoints are expressed as the trimethoprim concentration. 2. Breakpoints relate to S. saprophyticus only.
17
Enterococcus spp.
Penicillins1,2 MIC breakpoint (mg/L) S R>

1. Refer to national or international endocarditis guidelines for breakpoints for Enterococcus spp. in endocarditis. 2. E. faecium resistant to penicillins can be considered resistant to all other beta-lactam agents including carbapenems.
Benzylpenicillin Ampicillin Ampicillin-sulbactam3 Amoxicillin3 Amoxicillin-clavulanate3 Piperacillin3 Piperacillin-tazobactam3 Ticarcillin4 Ticarcillin-clavulanate

4
4 4 4 4 Note3 Note3 -
8 8 8 8 Note3 Note3 -
10 NoteA NoteA NoteA NoteA NoteA -
8 NoteA NoteA NoteA NoteA NoteA 3/A. Susceptibility to ampicillin, amoxicillin and pipercillin with and without beta-lactamase inhibitor can be inferred from the ampicillin susceptibility test.
4. Enterococcus spp. are intrinsically resistant to ticarcillin with or without clavulanate.
Phenoxymethylpenicillin
Carbapenems

8 -
10 21 18 -
4 -
Aminoglycosides

-
NoteA NoteA 1/A. Aminoglycoside monotherapy is ineffective against enterococci. There is synergism between aminoglycosides and beta-lactams against enterococci without acquired resistance mechanisms. There is no synergistic effect against enterococci with high-level aminoglycoside resistance, i.e with gentamicin MIC >128 mg/L or an inhibition zone diameter <8 mm with a gentamicin 30 g disk.
Amikacin1
Gentamicin1 Netilmicin1 Tobramycin1
Note1 -
Note1 -
30
NoteA NoteA NoteA
NoteA NoteA NoteA
18
Enterococcus spp.
Glycopeptides MIC breakpoint (mg/L) S
Teicoplanin 21

30 16A 16A 1. The S/I breakpoint for vancomycin has been raised to 4 mg/L to avoid dividing the wild type MIC distributions of some species. The I/R breakpoint for teicoplanin has been reduced to 2 mg/L to avoid discrepant 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. An alternative to disk diffusion is the agar screen method (Willey et al. J clin Microbiol 1992; 30: 1621-4) - BHI agar with vancomycin 6 mg/L; inoculum 1-10 L spot of 0.5 McFarland density suspension: incubate in air at 35C for 24 h; >1 colony indicates possible vancomycin resistance, which should be confirmed by MIC.
R>
2
Vancomycin
41
12A
12A

4
15 22A 20A 1/A. Quinupristin/dalfopristin breakpoints are valid for E. faecium only.
Azithromycin Clarithromycin Erythromycin Roxithromycin Telithromycin Clindamycin Quinupristin-dalfopristin1
19
Enterococcus spp.
Tetracyclines MIC breakpoint (mg/L) S
Doxycycline Minocycline Tetracycline Tigecycline 0.251

18 15
R>
0.5
15
1. Strains 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 must be sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC above the current resistant breakpoint they should be reported resistant.
Miscellaneous

IE 4 64 1 1
IE 10 100 19 15 5 1.25-23.75 50 50 IE 19 15 21 21 1. The activity of trimethoprim is uncertain against enterococci, hence the wild type population is categorized as intermediate. 2. Trimethoprim-sulfamethoxazole in the ratio 1:19. Breakpoints are expressed as the trimethoprim concentration.
Chloramphenicol Colistin Daptomycin Fosfomycin iv Fosfomycin-trometamol (uncomplicated UTI only) Fusidic acid Linezolid Metronidazole Nitrofurantoin (uncomplicated UTI only) Rifampicin Spectinomycin Trimethoprim (uncomplicated UTI only)
1
IE 4 64 0.03 0.03
Trimethoprim-sulfamethoxazole (co-trimoxazole) 2
20
Streptococcus groups A, B, C and G

Benzylpenicillin2 0.25

1 unit 18 18 1/A. The beta-lactam susceptibility of beta-haemolytic streptococcus groups A, B, C and G is inferred from the penicillin susceptibility. 2. Strains 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 must be sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC 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.
R>
0.25
Ampicillin Ampicillin-sulbactam3 Amoxicillin Amoxicillin-clavulanate Piperacillin

3
Note1 Note1 Note1 Note Note

1 1
Note1 Note1 Note1 Note Note

1 1
NoteA NoteA NoteA Note Note

A A
NoteA NoteA NoteA NoteA NoteA NoteA NoteA NA
Piperacillin-tazobactam3 Ticarcillin Ticarcillin-clavulanate Phenoxymethylpenicillin Oxacillin Cloxacillin Dicloxacillin Flucloxacillin
Note1 Note1 NA Note Note Note

1 1 1
Note1 Note1 NA Note Note Note

1 1 1
NoteA NoteA NA Note Note Note

A A A
NoteA NoteA NoteA
21

Cephalosporins1 MIC breakpoint (mg/L) S
Cefaclor Cefadroxil Cefalexin Cefazolin Cefepime Cefixime Cefotaxime Cefoxitin Cefpodoxime Ceftazidime Ceftibuten Ceftriaxone Cefuroxime Cefuroxime axetil Note1 Note Note Note 1

1/A. The beta-lactam susceptibility of beta-haemolytic streptococcus groups A, B, C and G is inferred from the penicillin susceptibility. Note1 Note Note Note 1
R>
NoteA Note Note Note A
NoteA NoteA NoteA NoteA NoteA NoteA NA NoteA NoteA NoteA NoteA NoteA
Note1
1 1
Note1
1 1
NoteA
A A
Note1 NA Note1 Note1 Note Note Note

1 1 1
Note1 NA Note1 Note1 Note Note Note

1 1 1
NoteA NA NoteA NoteA Note Note Note

A A A
Carbapenems

Note1 Note1 Note Note
1 1
NoteA NoteA Note Note
A A

1 1
NoteA NoteA NoteA NoteA
1/A. The beta-lactam susceptibility of beta-haemolytic streptococcus groups A, B, C and G is inferred from the penicillin susceptibility.
22

Fluoroquinolones MIC breakpoint (mg/L) S
Ciprofloxacin Levofloxacin Moxifloxacin Nalidixic acid Norfloxacin (screen) 1 0.5 NA NA

5 5 10 18 18 NA 12
A
R>
2 1 NA NA
15 15 NA 12A A. Screen for fluoroquinolone resistance using the norfloxacin disk. Isolates categorized as susceptible can be reported susceptible to levofloxacin and moxifloxacin. Isolates categorized as resistant should be tested for susceptibility to individual agents.
Ofloxacin
Glycopeptides

2
30 IPA IPA 1. Strains 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 must be sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC 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. There are problems in detection of low-level glycopeptide resistance with other organisms, where MIC methods have proved more reliable than disk diffusion.
Teicoplanin
21
Vancomycin
21
IPA
IPA

Azithromycin
1
R>
0.5 0.5 0.5 1 0.5 0.5 -
1/A. Erythromycin can be used to determine susceptibility to azithromycin, clarithromycin and roxithromycin. NoteA NoteA 15 15 2 21 NoteA IP 17B NoteA NoteA 18 NoteA IP 17B 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).
Clarithromycin1 Erythromycin Roxithromycin1 Telithromycin Clindamycin2 Quinupristin-dalfopristin
0.25 0.25 0.25 0.5 0.25 0.5 -
23

Tetracyclines1 MIC breakpoint (mg/L) S
Doxycycline1 Minocycline1 Tetracycline Tigecycline 1 0.5 1 0.25
2

NoteA 30 30 15 IPA 23 19 NoteA IPA 20 16 2. Strains 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 must be sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC above the current resistant breakpoint they should be reported resistant. 1/A. Isolates susceptible to tetracycline are also susceptible to doxycycline and minocycline. Some isolates resistant to tetracycline may be susceptible to minocycline and/or doxycycline.
R>
2 1 2 0.5

8 1
30 IP NoteA IP NoteA 1. Strains 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 must be sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC above the current resistant breakpoint they should be reported resistant. A. Test by MIC method only.
Chloramphenicol Colistin Daptomycin
8 11
Fosfomycin iv Fosfomycin-trometamol (uncomplicated UTI only) Fusidic acid Linezolid Metronidazole Nitrofurantoin (uncomplicated UTI only)2 Rifampicin Spectinomycin Trimethoprim (uncomplicated UTI only) Trimethoprim-sulfamethoxazole (co-trimoxazole)
3
IE 2 64 0.06 1
IE 4 64 0.5 2 1.25-23.75 10 100 5
IE 19 15 21 18
IE 16 15 15 15 3. Trimethoprim-sulfamethoxazole in the ratio 1:19. Breakpoints are expressed as the trimethoprim concentration. 2. Nitrofurantoin breakpoints apply to S. agalactiae (Group B streptococci) only.
24
Streptococcus pneumoniae

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 0.064 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 g disk. Isolates categorized as susceptible can be reported susceptible to benzylpenicillin, phenoxymethylpenicillin and aminopenicillins (with or without beta-lactamase inhibitor) irrespective of clinical indication. Isolates categorized as oxacillin resistant can be reported resistant to benzylpenicillin and phenoxymethylpenicillin in meningitis. For other beta-lactams, determine the MIC of the agent considered for clinical use.
Benzylpenicillin2
0.06
1 unit
NoteA
NoteA
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 2.0 mg/L should be regarded as susceptible. In meningitis, only isolates with MICs 0.06 mg/L (susceptible by oxacillin disk screen, see note A) should be categorized susceptible to benzylpenicillin, otherwise report resistant. For other indications, use breakpoints of 0.06/2 mg/L for categorization of benzylpenicillin susceptibility. See note A. 3/B. Isolates fully susceptible to benzylpenicillin (MIC0.064 mg/L; susceptible by oxacillin disk screen, see note A) can be reported susceptible to ampicillin, amoxicillin and piperacillin (with or without beta-lactamase inhibitor) without further testing. Otherwise use ampicillin to categorize susceptibility to ampicillin, amoxicillin and piperacillin.
Ampicillin1,3
0.5
28A,B
22A,B
Ampicillin-sulbactam Amoxicillin Amoxicillin-clavulanate Piperacillin Piperacillin-tazobactam Ticarcillin Ticarcillin-clavulanate Phenoxymethylpenicillin4
Note1,3 Note Note Note Note Note4

1,3 1,3 1,3 1,3
Note1,3 Note Note Note Note Note4

1,3 1,3 1,3 1,3
NoteA,B Note Note Note Note NoteA,C

A,B A,B A,B A,B
NoteA,B NoteA,B NoteA,B NoteA,B NoteA,B NoteA,C 4/C. Isolates fully susceptible to benzylpenicillin (MIC 0.064 mg/L; susceptible by oxacillin disk screen, see note A) can be reported susceptible to phenoxymethylpenicillin. Otherwise report as phenoxymethylpenicillin resistant without further testing.
Oxacillin (screen) Cloxacillin Dicloxacillin Flucloxacillin Mecillinam (uncomplicated UTI only)
NA -
NA -
20A -
20A -
25
Cephalosporins MIC breakpoint (mg/L) S
Cefaclor Cefadroxil Cefalexin Cefazolin Cefepime Cefixime Cefotaxime 0.03 1 0.51

30 50 30 32 NoteA 28 29 NoteA 1. Strains 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 above the current resistant breakpoint they should be reported resistant. A. Screen for beta-lactam resistance with the oxacillin 1 g disk. Isolates categorized as susceptible can be reported susceptible to cefepime, cefotaxime, cefpodoxime, ceftriaxone and cefuroxime and cefuroxime axetil. Isolates categorized as oxacillin resistant should be tested by an MIC method with the agent considered for clinical use.
R>
0.5 2 2
Cefoxitin Cefpodoxime Ceftazidime Ceftibuten Ceftriaxone Cefuroxime Cefuroxime axetil
NA 0.25 IE 0.51 0.5 0.25
NA 0.5 IE 2 1 0.5 10
NA 28 IE NoteA Note Note

A A
NA 25 IE NoteA NoteA NoteA
Carbapenems

1
NoteA NoteA 1. Not for meningitis (meropenem is the only carbapenem used for meningitis). 2. Strains 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 must be sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC above the current resistant breakpoint they should be reported resistant. A. Screen for beta-lactam resistance with the oxacillin 1 g disk. Isolates categorized as susceptible can be reported susceptible to doripenem, ertapenem, imipenem and meropenem. Isolates categorized as oxacillin resistant should be tested by an MIC method.
Doripenem1
12
Ertapenem1 Imipenem
1 3
0.52 2 2
2
0.5 2 2
NoteA Note Note

A A,B
NoteA NoteA NoteA,B 3. Meropenem is the only carbapenem used for meningitis. Meropenem breakpoints in meningitis are S 0.25 mg/L and R >1 mg/L. B. For use in meningitis determine the meropenem MIC.
Meropenem (infections other than meningitis)
26
Fluoroquinolones1 MIC breakpoint (mg/L) S R>

Disk Zone diameter Notes (numbers for comments on MIC breakpoints, letters for comments on disk diffusion) content breakpoint (mm) (g) S R<
1/A. Screen for fluoroquinolone resistance using the norfloxacin disk. Isolates categorized as susceptible can be reported susceptible to levofloxacin and moxifloxacin and intermediate to ciprofloxacin and ofloxacin. Isolates categorized as resistant should be tested for susceptibility to individual agents.
Ciprofloxacin2 Levofloxacin3 Moxifloxacin Nalidixic acid Norfloxacin (screen) Ofloxacin

4
0.12 2 0.5 NA NA 0.12
2 2 0.5 NA NA 4
5 5 5 10 5
IPA 19A 22A NA 12A 50

A
IPA 19A 22A NA 12A 15A
2. Wild type S. pneumoniae are not considered susceptible to ciprofloxacin and are therefore categorized as intermediate. 3. The breakpoints for levofloxacin relate to high dose therapy.
4. Wild type S. pneumoniae are not considered susceptible to ofloxacin and are therefore categorized as intermediate.
Glycopeptides

2 2
30 5 IP 15A IP 15A 1. Strains 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 must be sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC 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. There are problems in detection of low-level glycopeptide resistance with other organisms, where MIC methods have proved more reliable than disk diffusion
Teicoplanin Vancomycin
21 21
Macrolides1, lincosamides and streptogramins MIC breakpoint (mg/L) S R>
Azithromycin1 Clarithromycin Erythromycin

1
0.25 0.25 0.25 0.5 0.25 0.5 -
0.5 0.5 0.5 1 0.5 0.5 15 2 15
NoteA Note 22
A
NoteA NoteA 19 NoteA IP 19B -
1/A. Erythromycin can be used to determine susceptibility to azithromycin, clarithromycin and roxithromycin.
Roxithromycin1 Telithromycin Clindamycin2 Quinupristin-dalfopristin
NoteA IP 19B -
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).
27
Tetracyclines MIC breakpoint (mg/L) S
Doxycycline1 Minocycline1 Tetracycline Tigecycline 1 0.5 1 IE

NoteA 30 30 NoteA 23 IE NoteA NoteA 20 IE 1/A. Isolates susceptible to tetracycline are also susceptible to doxycycline and minocycline. Some isolates resistant to tetracycline may be susceptible to minocycline and/or doxycycline.
R>
2 1 2 IE

8 IE IE 4 0.5 2
30 20 IE IE 10 20 5 22 1.25-23.75 18 20 IE IE 20 17 15 1. Trimethoprim:sulfamethoxazole in the ratio 1:19. Breakpoints are expressed as the trimethoprim concentration.
Chloramphenicol Colistin Daptomycin Fosfomycin iv Fosfomycin-trometamol (uncomplicated UTI only) Fusidic acid Linezolid Metronidazole Nitrofurantoin (uncomplicated UTI only) Rifampicin Spectinomycin Trimethoprim (uncomplicated UTI only) Trimethoprim-sulfamethoxazole (co-trimoxazole)
1
8 IE IE 4 0.06 1
28
Other streptococci
Benzylpenicillin Ampicillin Ampicillin-sulbactam Amoxicillin Amoxicillin-clavulanate Piperacillin Piperacillin-tazobactam Ticarcillin Ticarcillin-clavulanate Phenoxymethylpenicillin Oxacillin Cloxacillin Dicloxacillin Flucloxacillin Mecillinam (uncomplicated UTI only) 0.25 0.5 Note1 0.5 Note1 Note Note IE IE IE 1 1

1. In endocarditis, refer to national or international endocarditis guidelines for breakpoints for viridans streptococci. 2 2 Note1 2 Note1 Note Note IE IE IE 1 1
R>
1 unit 2
18 21 NoteA NoteA NoteA Note Note IE IE IE A A
12 15 NoteA NoteA NoteA NoteA NoteA IE IE IE -
A. Use the ampicillin disk to categorize susceptibility to ampicillin, amoxicillin and piperacillin (with or without betalactamase inhibitor).
Cephalosporins1

0.5 0.5 0.5 NA 0.5 0.5 -
30 30 5 IP 25 23 NA 30 30 27 26 IP 25 23 NA 27 26 -
0.5 0.5 0.5 NA 0.5 0.5 -
29
Other streptococci
Doripenem 11

10 25 25 1. Strains 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 must be sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC above the current resistant breakpoint they should be reported resistant.
R>
1
Ertapenem Imipenem Meropenem
0.51 21 21
0.5 2 2
10 10 10
22 30 25
22 30 25
Fluoroquinolones

IE IE NA -
IE IE NA IE IE NA -
IE IE NA -
Glycopeptides

2
30 16A 16A 1. Strains 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 must be sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC 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. There are problems in detection of low-level glycopeptide resistance with other organisms, where MIC methods have proved more reliable than disk diffusion.
Teicoplanin
21
Vancomycin
21
15A
15A
30
Other streptococci
Macrolides, lincosamides and streptogramins MIC breakpoint (mg/L) S
Azithromycin Clarithromycin Erythromycin Roxithromycin Telithromycin Clindamycin1 Quinupristin-dalfopristin IE IE IE IE IE 0.5 IE

IE IE IE IE IE 2 19A IE IE IE IE IE IE 19A IE 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).
R>
IE IE IE IE IE 0.5 IE
Tetracyclines

IE
IE IE
IE
31
Haemophilus influenzae
Penicillins MIC breakpoint (mg/L) S
Benzylpenicillin Ampicillin1,2,3 IE 1

2 IE 16 IE 16 1. Always test for beta-lactamase and report positive strains resistant to penicillins without beta-lactamase inhibitors. 2. Breakpoints relate only to beta-lactamase negative strains. Strains may be resistant to penicillins, aminopenicillins and/or cephalosporins due to changes in PBPs (BLNAR, beta-lactamase negative ampicillin resistant) and a few strains have both resistance mechanisms (BLPACR, beta-lactamase positive, amoxicillin/clavulanate resistant). 3. Isolates susceptible to ampicillin and amoxicillin are also susceptible to piperacillin and piperacillin-tazobactam and isolates susceptible to amoxicillin-clavulanate are also susceptible to piperacillin-tazobactam. 4. For susceptibility testing purposes, the concentration of sulbactam is fixed at 4 mg/L. A. Susceptibility inferred from ampicillin. 5. For susceptibility testing purposes, the concentration of clavulanate is fixed at 2 mg/L. B. Susceptibility inferred from amoxicillin-clavulanate.
R>
IE 1
Ampicillin-sulbactam4 Amoxicillin1,2,3 Amoxicillin-clavulanate1,2,3,5 Piperacillin Piperacillin-tazobactam Ticarcillin Ticarcillin-clavulanate Phenoxymethylpenicillin (screen)
1 1 1 Note3 Note IE IE IE
3
1 1 1 Note3 Note IE IE IE
3
10-10 20-10
IP NoteA 20 NoteA Note IE IE

B
IP NoteA 20 NoteA NoteB IE IE 15C
10
NA
C. Phenoxymethylpenicillin can be used to screen for but not to distinguish between beta-lactamase producing H. influenzae and BLNAR. Check isolates categorized as resistant for beta-lactamase and non-beta-lactamase-mediated resistance to ampicillin and/or cephalosporins. See "Cephalosporins, note A".
Cephalosporins

0.5
30 NA 15A 1. MIC breakpoints render all H.influenzae resistant for cefaclor. A. The disk diffusion test can be used to screen for BLNAR. Isolates with zone diamaters <15 mm should be checked for ampicillin and cephalosporin resistance.
Cefaclor
0.51
Cefadroxil Cefalexin Cefazolin Cefepime
0.252
0.25 30
25
25 2. Strains 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 must be sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC above the current resistant breakpoint they should be reported resistant.
Cefixime Cefotaxime Cefoxitin Cefpodoxime Ceftazidime Ceftibuten Ceftriaxone Cefuroxime
0.122 0.12 NA
2
0.12 0.12 NA 0.5 1 0.12 2
5 5 30 30 30 30
22 22 NA 24 24 27 25
22 22 NA 21 24 27 22
0.252 12 0.122 1
32
Cefuroxime axetil 0.12 1 30 50 25

1
Carbapenems
10 20 20 1. Not for meningitis (meropenem is the only carbapenem used for meningitis). 2. Strains 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 must be sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC above the current resistant breakpoint they should be reported resistant.
Doripenem1
12
Ertapenem1 Imipenem
1
0.52 22 22
0.5 2 2
10 10 10
20 16 20A
20 16 20A 3. Meropenem is the only carbapenem used for meningitis. Meropenem breakpoints in meningitis are S 0.25 mg/L, R >1 mg/L. A. For use in meningitis determine the meropenem MIC value.
Meropenem (infections other than meningitis) 3
Monobactams

IE
IE IE
Aztreonam
IE
Fluoroquinolones1,2

0.5
5 23 23 1. Low-level fluoroquinolone resistance (ciprofloxacin MICs of 0.12-0.5 mg/L) may occur but there is no evidence that this resistance is of clinical importance in respiratory tract infections with H. influenzae . 2. Strains 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 must be sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC above the current resistant breakpoint they should be reported resistant.
Ciprofloxacin
0.52
Levofloxacin Moxifloxacin Nalidixic acid (screen)
12 0.52 NA
1 0.5 NA
5 5 30
21 23 23A
21 23 23A A. Screen for fluoroquinolone resistance. Isolates with zone diameters 23 mm can be reported susceptible to levofloxacin, ciprofloxacin, moxifloxacin and ofloxacin. Isolates with zone diameters <23 mm may have fluoroquinolone resistance and should be tested against the appropriate agent.
Norfloxacin Ofloxacin
0.52
0.5
21
21
33
Aminoglycosides MIC breakpoint (mg/L) S
Amikacin Gentamicin Netilmicin Tobramycin IE IE IE IE

IE IE IE IE IE IE IE IE
R>
IE IE IE IE

Azithromycin
1,2
R>
4 32 16 16 8 -
1/A. Erythromycin can be used to determine susceptibility to azithromycin, clarithromycin and roxithromycin. Note
A
0.12 1 0.5 1 0.12 -
Note
2. Correlation between macrolide MICs and clinical outcome is weak for H. influenzae . Therefore, breakpoints for macrolides and related antibiotics have been set to categorize wild type H. influenzae as intermediate.
Clarithromycin1,2 Erythromycin Roxithromycin Telithromycin Clindamycin Quinupristin-dalfopristin

2 1,2
15 15
NoteA 50 NoteA IP -
NoteA 12 NoteA IP -
Tetracyclines1

2 2 2 IE
NoteA 30 30 IPA 24 IE NoteA IPA 21 IE 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.
Doxycycline1 Minocycline1 Tetracycline Tigecycline
1 1 1 IE
34
Miscellaneous agents MIC breakpoint (mg/L) S
Chloramphenicol Colistin Daptomycin Fosfomycin iv Fosfomycin-trometamol (uncomplicated UTI only) Fusidic acid Linezolid Metronidazole Nitrofurantoin (uncomplicated UTI only) Rifampicin Spectinomycin Trimethoprim (uncomplicated UTI only) Trimethoprim-sulfamethoxazole (co-trimoxazole) 1 1 IE 0.5 0.5

30 28 IE 5 18 1.25-23.75 23 25 IE 18 20 1. Trimethoprim:sulfamethoxazole in the ratio 1:19. Breakpoints are expressed as the trimethoprim concentration.
R>
2 IE 0.5 1
35
Moraxella catarrhalis
Penicillins MIC breakpoint (mg/L) S
Benzylpenicillin Ampicillin1 1

10 IPA IPA 1/A. 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/B. Susceptibility inferred from amoxicillin-clavulanate. 4. For susceptibility testing purposes, the concentration of clavulanate is fixed at 2 mg/L.
R>
1
Ampicillin-sulbactam2,3 Amoxicillin1 Amoxicillin-clavulanate Piperacillin1 Piperacillin-tazobactam Ticarcillin Ticarcillin-clavulanate Phenoxymethylpenicillin

3 4
1 1 1 IP IP IE IE -
1 1 1 IP IP IE IE -
10-10 10 20-10 30 30-6
IPB IPA IP
B
IPB IPA IPB IPA IPB IE IE -
IPA IP IE IE B
Cephalosporins

0.5 0.25
30 IP 30 IP IP IP 1. Strains 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 must be sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC above the current resistant breakpoint they should be reported resistant.
Cefaclor Cefadroxil Cefalexin Cefazolin Cefepime
0.5 0.251
Cefixime Cefotaxime Cefoxitin Cefpodoxime Ceftazidime Ceftibuten Ceftriaxone Cefuroxime Cefuroxime axetil
0.51 1 NA 0.251 11 11 1 0.12

1
1 2 NA 0.5 1 2 2 2
5 5 30 30 30 30 30
IP IP NA IP IP IP IP IP
IP IP NA IP IP IP IP IP
36
Doripenem 11

10 IP IP 1. Strains 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 must be sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC above the current resistant breakpoint they should be reported resistant.
R>
1
Ertapenem Imipenem Meropenem
0.51 21 21
0.5 2 2
10 10 10
IP IP IP
IP IP IP
Monobactams

IE
IE IE
Aztreonam
IE
Fluoroquinolones1
1. Strains 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 must be sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC above the current resistant breakpoint they should be reported resistant.
0.51 11 0.51 NA 0.51
0.5 1 0.5 NA 0.5
5 5 5
23 IP IP NA IP
23 IP IP NA IP
Aminoglycosides

IE IE IE IE
IE IE IE IE
37
Azithromycin1 Clarithromycin1 Erythromycin Roxithromycin Telithromycin
1

1/A. Erythromycin can be used to determine susceptibility to azithromycin, clarithromycin and roxithromycin. 0.5 0.25 0.25 0.5 0.25 0.5 0.5 0.5 1 0.5 15 15 NoteA NoteA 21 NoteA IP NoteA NoteA 18 NoteA IP -
R>
Clindamycin Quinupristin-dalfopristin
Tetracyclines

2 2 2 IE
NoteA 30 30 IPA 28 IE NoteA IPA 25 IE 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.
1 1 1 IE

2 IE 0.5 1
30 IP IE 5 IP 1.25-23.75 18 IP IE IP 15 1. Trimethoprim:sulfamethoxazole in the ratio 1:19. Breakpoints are expressed as the trimethoprim concentration.
1
1 IE 0.5 0.5
38
Disk diffusion criteria for antimicrobial susceptibility testing of Neisseria gonorrhoeae have not yet been determined.
Neisseria gonorrhoeae
Penicillins1

MIC breakpoint Notes Numbers for comments on MIC breakpoints (mg/L) Letters for comments on disk diffusion R> 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 Ampicillin1 Ampicillin-sulbactam Amoxicillin1 Amoxicillin-clavulanate Piperacillin Piperacillin-tazobactam Ticarcillin Ticarcillin-clavulanate Phenoxymethylpenicillin
0.06 Note1 IE Note1 Note 1
1 Note1 IE Note1 Note1 -
Cephalosporins
0.12 0.12 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.
Cefaclor Cefadroxil Cefalexin Cefazolin Cefepime Cefixime1
Cefotaxime Cefoxitin Cefpodoxime Ceftazidime Ceftibuten Ceftriaxone Cefuroxime Cefuroxime axetil
0.12 IE IE 0.12 -
0.12 IE IE 0.12 -
39
Carbapenems

Monobactams
IE IE
Aztreonam
Fluoroquinolones1
0.03 IE IE NA IE 0.12 0.06 IE IE NA IE 0.25
Macrolides1, lincosamides and streptogramins
0.25 0.5 -
Azithromycin Clarithromycin Erythromycin Roxithromycin Telithromycin Clindamycin Quinupristin-dalfopristin
40
Tetracyclines1

IE 0.5 0.5 IE IE 1 1 IE 1. Isolates susceptible to tetracycline are also susceptible to doxycycline and minocycline, but some resistant to tetracycline may be susceptible to minocycline and/or doxycycline.
64 64 -
41
Disk diffusion criteria for antimicrobial susceptibility testing of Neisseria meningitidis have not yet been determined.
Neisseria meningitidis
Penicillins

0.06 0.12 IE 0.12 0.25 1 IE 1 -
Benzylpenicillin Ampicillin Ampicillin-sulbactam Amoxicillin Amoxicillin-clavulanate Piperacillin Piperacillin-tazobactam Ticarcillin Ticarcillin-clavulanate Phenoxymethylpenicillin
Cephalosporins
0.121 0.12
Cefaclor Cefadroxil Cefalexin Cefazolin Cefepime Cefixime Cefotaxime
1. Strains 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 above the current resistant breakpoint they should be reported resistant.
Cefoxitin Cefpodoxime Ceftazidime Ceftibuten Ceftriaxone Cefuroxime Cefuroxime axetil 0.121 0.12 -
42
Carbapenems

IE 0.252 IE 0.25 1. Strains 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 above the current resistant breakpoint they should be reported resistant. 2. Breakpoints relate to meningitis only.
Doripenem Ertapenem Imipenem Meropenem1
Fluoroquinolones
0.031 IE IE NA IE 0.061 IE IE NA IE 1. Breakpoints apply only to use in the prophylaxis of meningococcal disease.
Tetracyclines
1 1 IE 2 2 IE 1. Tetracycline can be used to predict susceptibility to minocycline for prophylaxis against N. meningitidis infections.
Doxycycline Minocycline
1
Tetracycline Tigecycline
43

2 0.25 4 0.25 1. For prophylaxis of meningitis only (refer to national guidelines).
44
Disk diffusion criteria for antimicrobial susceptibility testing of anaerobes have not yet been determined.
Gram-positive anaerobes
Penicillins

0.25 4 4 4 4 8 8 8 8 IE 0.5 8 8 8 8 16 16 16 16 IE 1. Susceptibility to ampicillin, amoxicillin and piperacillin without beta-lactamase inhibitors can be inferred from susceptibility to benzylpenicillin.
Benzylpenicillin1 Ampicillin Ampicillin-sulbactam Amoxicillin Amoxicillin-clavulanate Piperacillin Piperacillin-tazobactam Ticarcillin Ticarcillin-clavulanate Phenoxymethylpenicillin
Carbapenems
1 1 2 2 1 1 8 8
Fluoroquinolones
IE NA IE NA -
45
Glycopeptides

2 2
IE 4 IE 4 -
Azithromycin Clarithromycin Erythromycin Roxithromycin Telithromycin Clindamycin Quinupristin/dalfopristin
Tetracyclines1
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.
Doxycycline1 Minocycline1 Tetracycline1 Tigecycline1
46

8 4 8 4 -
47
Disk diffusion criteria for antimicrobial susceptibility testing of anaerobes have not yet been determined.
Gram-negative anaerobes
Penicillins

0.25 0.5 0.5 2 8 2 8 16 16 16 16 IE 1. Susceptibility to ampicillin, amoxicillin and piperacillin without beta-lactamase inhibitors can be inferred from susceptibility to benzylpenicillin.
Benzylpenicillin1 Ampicillin1 Ampicillin-sulbactam Amoxicillin1 Amoxicillin-clavulanate1 Piperacillin1 Piperacillin-tazobactam Ticarcillin

1 1 1
4 0.5 4 16 8 16 8 IE
Ticarcillin-clavulanate1 Phenoxymethylpenicillin
Carbapenems
1 1 2 2 1 1 8 8
Monobactams
-
Aztreonam
48
Fluoroquinolones

IE NA IE NA -
IE IE
4 -
4 -
Tetracyclines1
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.

1 1

1 1
49

8 4 8 4 -
50
Non-species related breakpoints

Penicillins
Benzylpenicillin Ampicillin Ampicillin-sulbactam Amoxicillin Amoxicillin-clavulanate Piperacillin Piperacillin-tazobactam Ticarcillin Ticarcillin-clavulanate Phenoxymethylpenicillin Oxacillin Cloxacillin Dicloxacillin Flucloxacillin Mecillinam (uncomplicated UTI only)

MIC breakpoint R> S
0.25 2 2 2 2 4 4 8 8 IE IE IE IE IE IE 2 8 8 8 8 16 16 16 16 IE IE IE IE IE IE
Cephalosporins
MIC breakpoint S R>

IE IE IE 1 4 IE 1 IE IE 4 IE 1 4 IE IE IE IE 2 8 IE 2 IE IE 8 IE 2 8 IE
51

Carbapenems

MIC breakpoint R> S
1 0.5 2 2 4 1 8 8
Monobactams
Aztreonam
MIC breakpoint R> S

4 8
Fluoroquinolones
MIC breakpoint R> S

0.5 1 0.5 NA 0.5 0.5 1 2 1 NA 1 1
Aminoglycosides
MIC breakpoint S R>

8 2 2 2 16 4 4 4
Glycopeptides
MIC breakpoint S R>

2 2 4 4
52


MIC breakpoint S R>
IE IE IE IE IE IE IE IE IE IE IE IE IE IE
Tetracyclines
MIC breakpoint S R>

IE IE IE 0.25 IE IE IE 0.5
Miscellaneous
MIC breakpoint S R>

IE IE IE IE IE IE 2 IE IE IE IE IE IE IE IE IE IE IE IE 4 IE IE IE IE IE IE
53

European Committee On Antimicrobial Susceptibility Testing

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European Committee On Antimicrobial Susceptibility Testing

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European Committee on Antimicrobial Susceptibility Testing

Breakpoint tables for interpretation of MICs and zone diameters

European Committee on Antimicrobial Susceptibility Testing

Abbreviations and definitions

European Committee on Antimicrobial Susceptibility Testing

Pseudomonas spp. Staphylococcus spp.

Enterococcus spp. Streptococcus A, B, C and G

EUCAST Clinical Breakpoint Table v. 1.1 2010-04-27

Note1 Note1 Note1 8 8 8 8 8

10-10 20-10 30 30-6 75 75-10

MIC breakpoint (mg/L) S R>

EUCAST Clinical Breakpoint Table v. 1.1 2010-04-27

Doripenem Ertapenem Imipenem2 Meropenem

MIC breakpoint (mg/L) S R>

MIC breakpoint (mg/L) S R>

Levofloxacin Moxifloxacin Nalidixic acid (screen)

EUCAST Clinical Breakpoint Table v. 1.1 2010-04-27

Macrolides, lincosamides and streptogramins

MIC breakpoint (mg/L) S R>

MIC breakpoint (mg/L) S R>

Doxycycline Minocycline Tetracycline Tigecycline1

MIC breakpoint (mg/L) S R>

1. Breakpoints relate to E. coli only.

EUCAST Clinical Breakpoint Table v. 1.1 2010-04-27

MIC breakpoint (mg/L) S R>

EUCAST Clinical Breakpoint Table v. 1.1 2010-04-27

MIC breakpoint (mg/L) S R>

MIC breakpoint (mg/L) S R>

Ciprofloxacin Levofloxacin Moxifloxacin Nalidixic acid Norfloxacin Ofloxacin

MIC breakpoint (mg/L) S R>

Amikacin Gentamicin Netilmicin Tobramycin

EUCAST Clinical Breakpoint Table v. 1.1 2010-04-27

EUCAST Clinical Breakpoint Table v. 1.1 2010-04-27

MIC breakpoint (mg/L) S R>

Doripenem Ertapenem Imipenem Meropenem

MIC breakpoint (mg/L) S R>

EUCAST Clinical Breakpoint Table v. 1.1 2010-04-27

MIC breakpoint (mg/L) S R>

Amikacin Gentamicin Netilmicin Tobramycin

MIC breakpoint (mg/L) S R>

Doxycycline Minocycline Tetracycline Tigecycline

EUCAST Clinical Breakpoint Table v. 1.1 2010-04-27

EUCAST Clinical Breakpoint Table v. 1.1 2010-04-27

B. Breakpoints relate to S. saprophyticus only.

EUCAST Clinical Breakpoint Table v. 1.1 2010-04-27

Note1 Note1 Note1 Note1 Note1 Note1 Note3

Note1 Note1 Note1 Note1 Note1 Note1 Note3 30

NoteA NoteA NoteA NoteA NoteA NoteA 22A

NoteA NoteA NoteA NoteA NoteA NoteA 22A

25A NoteA IE NoteA NoteA NoteA

Note1 Note1 Note1

Note1 Note1 Note1

NoteA NoteA NoteA

MIC breakpoint (mg/L) S R>

Doripenem Ertapenem Imipenem Meropenem

Note1 Note1 Note1 Note1

EUCAST Clinical Breakpoint Table v. 1.1 2010-04-27

MIC breakpoint (mg/L) S R>

Amikacin2 Gentamicin Netilmicin Tobramycin

MIC breakpoint (mg/L) S R>

Teicoplanin, S. aureus, S.lugdunensis

Teicoplanin, Coagulase-negative staphylococci Vancomycin1

EUCAST Clinical Breakpoint Table v. 1.1 2010-04-27