EUCAST Expert Rules Version 3.

Intrinsic Resistance and Exceptional Phenotypes Tables

EUCAST Expert Rules version 2.0 was published on 29 October 2011(http://www.eucast.org/expert_rules). The expert rules have been under
review over the past year and changes to the intrinsic resistance and exceptional phenotypes tables have been agreed following wide
consultation (October-December 2015) and further discussion in the EUCAST Steering Committee. The revised intrinsic resistance and
exceptional phenotypes tables 1-7 (version 3.0), together with a summary of changes from version 2.0, were published on 9 September 2016.
Version 3.1includes corrections to typographical errors in version 3.0.

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Summary of changes

Table Antimicrobial agent / microorganisms Modification

or rule
All Expert rules have been renumbered when needed as well as footnotes

Table 1 Ampicillin-sulbactam Added and R included for different microorganisms

Piperacillin R removed for C. koseri and consequently piperacillin column removed
All first generation cephalosporins with Added
breakpoints in the breakpoint table (v6)
Cefoxitin A note and R for H. alvei and S. marcescens added
Cefuroxime R removed for M. morgannii and added for Providencia stuartii and P. rettgerii
Cefamandole Deleted
Aminoglycosides Notes for S. marcescens and P. stuartii deleted and consequently aminoglycosides column removed
Tetracyclines and tigecycline They appear now separately. A note added for S. marcescens
Tigecycline R removed for M. morganii
Citrobacter freundii, Citrobacter koseri Nomenclature reviewed and phenotypes modified accordingly. A note added
Enterobacter cloacae Indicated as Enterobacter cloacae complex
Klebsiella spp. It now appears in two lines, one for K. pneumoniae and another for K. oxytoca
Raoultella spp. Added
Notes Modified

Table 2 Heading Partially reworded

Amoxicillin-clavulanic acid R added for Elizabethkingia meningoseptica
Ampicillin-sulbactam Added
All first generation cephalosporins with Added
breakpoints in the breakpoint table (v6)
Ceftazidime R deleted for Stenotrophomonas maltophilia
Cefepime Added and R included for Elizabethkingia meningoseptica and Ochrobactrum anthropi
Aztreonam Added
Imipenem Deleted for B. cepacia
Tetracyclines and tigecycline Now in separate columns. A note has been added for S. maltophilia
Trimethoprim Note e removed
Trimethoprim-sulfamethoxazole Deleted
Acinetobacter Now referred to as A. baumannii, A. pittii and A. nosocomialis, and A. calcoaceticus complex. R added for
tetracycline, with a note. This note also relates to tigecycline. A note added for ampicillin-sulbactam.
Burkholderia cepacia complex R added for piperacillin, piperacillin-tazobactam, cefotaxime and ceftriaxone

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 Elizabethkingia meningoseptica R added for piperacillin
Notes Modified

Table 3 Macrolides Deleted

Streptogramins R added for H. influenzae
"I" category Deleted as a note

Table 4 Ceftazidime R added for Streptococcus spp.

Macrolides Macrolides instead erythromycin
Staphylococcus xylosus Included in a separate line from Staphylococcus cohnii
Lactobacillus spp. Lactobacillus species that are typically resistant to vancomycin, L. casei and L. casei var. rhamnosus, have
been added
Notes Arbekacin deleted from note b. The AAC(6’) enzyme named as AAC(6’)-I

Table 5 All Only unusual resistant phenotypes are now included. Unusual susceptible phenotypes have been deleted
Meropenem and/or imipenem Exceptional meropenem and/or imipenem resistance in Enterobacteriaceae has been removed
Colistin New rule on exceptional colistin resistance in Enterobacteriaceae with notes
Salmonella typhi New rule on exceptional fluoroquinolone and/or carbapenem resistance
N. gonorrhoeae Deletion of resistance to third generation cephalosporins. Azithromycin added.
Moraxella catarrhalis Fluoroquinolones instead ciprofloxacin
Note Note has been modified

Table 6 Various organisms Some of the exceptional phenotypes have been reworded. For all species except enterococci exceptional
resistance to telavancin, dalbavancin, oritavancin, tedizolid has been added.
JK coryneform Modified to Corynebacterium spp.
E. faecalis Exceptional resistance to ampicillin has been added
E. faecium Exceptional resistance to quinupristin-dalfopristin has been removed
Note Note has been modified

Table 7. Bacteroides spp. Exceptional carbapenem resistance has been deleted

C. difficile Exceptional resistance to fidaxomicin has been added

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Table 1. Intrinsic resistance in Enterobacteriaceae. Enterobacteriaceae are also intrinsically resistant to benzylpenicillin, glycopeptides, fusidic acid,
1
macrolides (with some exceptions ), lincosamides, streptogramins, rifampicin, daptomycin and linezolid.

Ampicillin-sulbactam

Cefalexin, Cefadroxil
Cefazolin, Cefalotin
Clavulanic acid

Nitrofurantoin
Tetracyclines

Polymyxin B,
Cefuroxime

Tigecycline
Amoxicilin-
Ampicillin

Ticarcillin

2
Cefoxitin

Colistin
Rule Organisms
no.

3
1.1 Citrobacter koseri,Citrobacter amalonaticus R R
4
1.2 Citrobacter freundii R R R R R
1.3 Enterobacter cloacae complex R R R R R
1.4 Enterobacter aerogenes R R R R R
1.5 Escherichia hermannii R R
1.6 Hafnia alvei R R R R R
1.7 Klebsiella pneumoniae R R
1.8 Klebsiella oxytoca R R
1.9 Morganella morganii R R R R R R R
1.10 Proteus mirabilis R R R R
1.11 Proteus penneri R R R R R R R
1.12 Proteus vulgaris R R R R R R R
1.13 Providencia rettgeri R R R R R R R R R
1.14 Providencia stuartii R R R R R R R R R
1.15 Raoultella spp. R R
5
1.16 Serratia marcescens R R R R R R R R R
1.17 Yersinia enterocolitica R R R R R R
1.18 Yersinia pseudotuberculosis R
R = resistant

1
Azithromycin is effective in vivo for the treatment of typhoid fever and erythromycin may be used to treat travellers’ diarrhoea.

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 Clinical breakpoints for cefoxitin have not been defined. Enterobacteriaceae species intrinsically resistant to this antibiotic produce a chromosomal inducible AmpC β-lactamase (AmpC)
2

that is responsible for higher cefoxitin MIC values when compared with those from Enterobacteriaceae species lacking this β-lactamase production.
3
Also includes Citrobacter sedlakii, Citrobacter farmeri and Citrobacter rodentium.
4
Also includes Citrobacter braakii, Citrobacter murliniae, Citrobacter werkmanii and Citrobacter youngae.
5
Serratia marcescens is intrinsically resistant to tetracycline and doxycycline but not to minocycline or tigecycline.

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 Table 2. Intrinsic resistance in non-fermentative Gram-negative bacteria. Non-fermentative Gram-negative bacteria are also generally intrinsically resistant to
benzylpenicillin, first and second generation cephalosporins, glycopeptides, fusidic acid, macrolides, lincosamides, streptogramins, rifampicin, daptomycin
and linezolid

Amoxicillin-Clavulanic acid

Ticarcillin-clavulanic acid

Piperacillin-tazobactam
Ampicillin-sulbactam

Polymyxin B/Colistin
Cefazolin, Cefalothin
Cefalexin, Cefadroxil
Rule

Aminoglycosides
Chloramphenicol
Organisms
no.

Trimethoprim

Tetracyclines
Ciprofloxacin
Ceftazidime

Meropenem

Fosfomycin
Ceftriaxone

Tigecycline
Cefotaxime
Piperacillin

Aztreonam
Ertapenem
Ampicillin

Ticarcillin

Imipenem
Cefepime
Acinetobacter baumannii,
Acinetobacter pittii, Acinetobacter 1 2 2
2.1 R R Note R R R R R R R R Note
nosocomialis and Acinetobacter
calcoaceticus complex
2.2 Achromobacter xylosoxydans R R R R R
3 4
2.3 Burkholderia cepacia complex R R R R R R R R R R R R R R R R R R
2.4 Elizabethkingia meningoseptica R R R R R R R R R R R R R R R R
2.5 Ochrobactrum anthropi R R R R R R R R R R R R R R
5
2.6 Pseudomonas aeruginosa R R R R R R R R Note R R R
4 6 7
2.7 Stenotrophomonas maltophilia R R R R R R R R R R R R R R R R R
R = resistant
1
Acinetobacter baumannii may appear to be susceptible to ampicillin-sulbactam due to activity of sulbactam with this species.
2
Acinetobacter is intrinsically resistant to tetracycline and doxycycline but not to minocycline and tigecycline.
Burkholderia cepacia complex includes different species. Some strains may appear susceptible to some β-lactams in vitro but they are clinically resistant and are shown as R in the table.
3

4
Burkholderia cepacia and Stenotrophomonas maltophilia are intrinsically resistant to all aminoglycosides. Intrinsic resistance is attributed to poor permeability and putative efflux. In
addition, most Stenotrophomonas maltophilia produce the AAC(6’)Iz enzyme.
5
Pseudomonas aeruginosa is intrinsically resistant to kanamycin and neomycin due to low level APH(3’)-IIb activity.
6
Stenotrophomonas maltophilia typically is susceptible to trimethoprim-sulfamethoxazole, but resistant to trimethoprim alone.
7
Stenotrophomonas maltophilia is intrinsically resistant to tetracycline but not to doxycycline, minocycline and tigecycline.

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 Table 3. Intrinsic resistance in Gram-negative bacteria other than Enterobacteriaceae and non-fermentative Gram-negative bacteria. Gram-negative bacteria
other than Enterobacteriaceae and non-fermentative Gram-negative bacteria listed are also intrinsically resistant to glycopeptides, lincosamides, daptomycin
and linezolid.

Streptogramins

Trimethoprim

Nalidixic acid
Fusidic acid
Rule
Organisms
no.

3.1 Haemophilus influenzae R R

3.2 Moraxella catarrhalis R
3.3 Neisseria spp. R
3.4 Campylobacter fetus R R R R
3.5 Campylobacter jejuni, Campylobacter coli R R R
R = resistant

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 Table 4. Intrinsic resistance in Gram-positive bacteria. Gram-positive bacteria are also intrinsically resistant to aztreonam, temocillin, polymyxin B/colistin
and nalidixic acid

(except ceftazidime)

Aminoglycosides
Cephalosporins

Sulfonamides
Quinupristin-
Rule

Clindamycin

Vancomycin
Fusidic acid

Ceftazidime

Fosfomycin
Teicoplanin
dalfopristin

Novobiocin
Organisms

Macrolides
no.

4.1 Staphylococcus saprophyticus R R R R

4.2 Staphylococcus cohnii, R R
4.3 Staphylococcus xylosus R R
4.4 Staphylococcus capitis R R
Other coagulase-negative staphylococci and
4.5 R
Staphylococcus aureus
1
4.6 Streptococcus spp. R R R
1
4.7 Enterococcus faecalis R R R R R R R R
1
4.8 Enterococcus gallinarum, Enterococcus casseliflavus R R R R R R R R R
1,2
4.9 Enterococcus faecium R R R R R R
4.10 Corynebacterium spp. R
4.11 Listeria monocytogenes R R
4.12 Leuconostoc spp., Pediococcus spp. R R
4.13 Lactobacillus spp. (L. casei, L. casei var. rhamnosus) R R
4.14 Clostridium ramosum, Clostridium innocuum R
R = resistant
1
Low-level resistance (LLR) to aminoglycosides. Combinations of aminoglycosides with cell wall inhibitors (penicillins and glycopeptides) are synergistic and bactericidal against isolates
that are susceptible to cell wall inhibitors and do not display high-level resistance to aminoglycosides.
2
In addition to LLR to aminoglycosides, Enterococcus faecium produces a chromosomal AAC(6’)-I enzyme that is responsible for the loss of synergism between aminoglycosides (except
gentamicin, amikacin and streptomycin) and penicillins or glycopeptides.

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Table 5. Exceptional resistance phenotypes of Gram-negative bacteria

Rule
Organisms Exceptional phenotypes
no.
Any Enterobacteriaceae (except Proteeae and 1,2
5.1 Resistant to colistin
Serratia marcescens)
5.2 Salmonella Typhi Resistant to fluoroquinolones and/or carbapenems
1
5.3 Pseudomonas aeruginosa and Acinetobacter spp. Resistant to colistin
5.4 Haemophilus influenzae Resistant to any third-generation cephalosporin, carbapenems, fluoroquinolones
5.5 Moraxella catarrhalis Resistant to any third-generation cephalosporin and/or fluoroquinolones
5.6 Neisseria meningitidis Resistant to any third generation cephalosporins and/or fluoroquinolones
5.7 Neisseria gonorrhoeae Resistant to spectinomycin and/or azithromycin

Except in countries where colistin resistance is not rare. Colistin MICs for some Salmonella serotypes are slightly above the breakpoint (S ≤2; R >2 mg/L).
1 2

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Table 6. Exceptional resistance phenotypes of Gram-positive bacteria

Rule
Organisms Exceptional phenotypes
no.
Resistant to vancomycin, teicoplanin, telavancin, dalbavancin, oritavancin, daptomycin,
6.1 Staphylococcus aureus
linezolid, tedizolid, quinupristin-dalfopristin and/or tigecycline.
1
Resistant to vancomycin, telavancin, dalbavancin, oritavancin, daptomycin, linezolid ,
6.2 Coagulase-negative staphylococci 1 1
tedizolid , quinupristin-dalfopristin and/or tigecycline.
Resistant to vancomycin, teicoplanin, telavancin, dalbavancin, oritavancin, daptomycin,
6.3 Corynebacterium spp.
linezolid, tedizolid, quinupristin-dalfopristin and/or tigecycline.
6.4 Resistant to carbapenems, vancomycin, teicoplanin, telavancin, dalbavancin, oritavancin,
Streptococcus pneumoniae
daptomycin, linezolid, tedizolid, quinupristin-dalfopristin, tigecycline and/or rifampicin.
Resistant to penicillin, cephalosporins, vancomycin, teicoplanin, telavancin, dalbavancin,
6.5 Group A, B, C and G β-haemolytic streptococci
oritavancin, daptomycin, linezolid, tedizolid, quinupristin-dalfopristin and/or tigecycline.
Resistant to daptomycin, linezolid and/or tigecycline.
6.6 Enterococcus spp.
Resistant to teicoplanin but not vancomycin.
6.7 Enterococcus faecalis Resistant to ampicillin
Enterococcus faecalis, Enterococcus gallinarum, Susceptible to quinupristin-dalfopristin, consider misidentification. If also resistant to ampicillin
6.8
Enterococcus casseliflavus, Enterococcus avium it is almost certainly E. faecium.

1
Except in countries where linezolid, tedizolid or quinupristin-dalfopristin resistant coagulase-negative staphylococci are not rare.

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Table 7. Exceptional resistance phenotypes of anaerobes

Rule
Organisms Exceptional phenotypes
no.
7.1 Bacteroides spp. Resistant to metronidazole
7.2 Clostridium difficile Resistant to metronidazole, vancomycin and/or fidaxomicin

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