EUCAST Expert Rules Version 3.1. Intrinsic Resistance and Exceptional Phenotypes Tables

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EUCAST Expert s Version 3.1 Intrinsic Resistance and Exceptional Phenotypes Tables EUCAST Expert s version 2.0 was published on 29 October 2011(http://www.eucast.org/expert_rules).

1 EUCAST Expert s Version 3.1 Intrinsic Resistance and Exceptional Phenotypes Tables EUCAST Expert s version 2.0 was published on 29 October 2011( 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 Version 3.1includes corrections to typographical errors in version 3.0. EUCAST intrinsic resistance and exceptional phenotypes, Expert s version September 2016 Page 1 of 11

2 Summary of changes Table All Antimicrobial agent / microorganisms or rule Modification 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 Amoxicillin-clavulanic acid Partially reworded R added for Elizabethkingia meningoseptica Ampicillin-sulbactam Added All first generation cephalosporins with breakpoints in the breakpoint table (v6) Added 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 EUCAST intrinsic resistance and exceptional phenotypes, Expert s version September 2016 Page 2 of 11

3 Elizabethkingia meningoseptica Notes R added for piperacillin 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 EUCAST intrinsic resistance and exceptional phenotypes, Expert s version September 2016 Page 3 of 11

4 Table 1. Intrinsic resistance in Enterobacteriaceae. Enterobacteriaceae are also intrinsically resistant to benzylpenicillin, glycopeptides, fusidic acid, macrolides (with some exceptions 1 ), lincosamides, streptogramins, rifampicin, daptomycin and linezolid. Ampicillin Amoxicilin- Clavulanic acid Ampicillin-sulbactam Ticarcillin Cefazolin, Cefalotin Cefalexin, Cefadroxil Cefoxitin 2 Cefuroxime Tetracyclines Tigecycline Polymyxin B, Colistin Nitrofurantoin 1.1 Citrobacter koseri,citrobacter amalonaticus 3 R R 1.2 Citrobacter freundii 4 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 1.16 Serratia marcescens R R R R R R R 5 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. EUCAST intrinsic resistance and exceptional phenotypes, Expert s version September 2016 Page 4 of 11

5 2 Clinical breakpoints for cefoxitin have not been defined. Enterobacteriaceae species intrinsically resistant to this antibiotic produce a chromosomal inducible AmpC β-lactamase (AmpC) 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. EUCAST intrinsic resistance and exceptional phenotypes, Expert s version September 2016 Page 5 of 11

6 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 Ampicillin Amoxicillin-Clavulanic acid Ampicillin-sulbactam Ticarcillin Ticarcillin-clavulanic acid Piperacillin Piperacillin-tazobactam Cefazolin, Cefalothin Cefalexin, Cefadroxil Cefotaxime Ceftriaxone Ceftazidime Cefepime Aztreonam Ertapenem Imipenem Meropenem Ciprofloxacin Chloramphenicol Aminoglycosides Trimethoprim Fosfomycin Tetracyclines Tigecycline Polymyxin B/Colistin Acinetobacter baumannii, Acinetobacter pittii, Acinetobacter 2.1 nosocomialis and Acinetobacter calcoaceticus complex R R Note 1 R R R R R R R R 2 Note Achromobacter xylosoxydans R R R R R 2.3 Burkholderia cepacia complex 3 R R R R R R R R R R R R R R R 4 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 2.6 Pseudomonas aeruginosa R R R R R R R R Note 5 R R R 2.7 Stenotrophomonas maltophilia R R R R R R R R R R R R R R 4 R 6 R R 7 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. 3 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. 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. EUCAST intrinsic resistance and exceptional phenotypes, Expert s version September 2016 Page 6 of 11

7 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. Fusidic acid Streptogramins Trimethoprim Nalidixic acid 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 EUCAST intrinsic resistance and exceptional phenotypes, Expert s version September 2016 Page 7 of 11

8 Table 4. Intrinsic resistance in Gram-positive bacteria. Gram-positive bacteria are also intrinsically resistant to aztreonam, temocillin, polymyxin B/colistin and nalidixic acid Fusidic acid Ceftazidime Cephalosporins (except ceftazidime) Aminoglycosides Macrolides Clindamycin Quinupristindalfopristin Vancomycin Teicoplanin Fosfomycin Novobiocin Sulfonamides 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 4.5 Other coagulase-negative staphylococci and Staphylococcus aureus 4.6 Streptococcus spp. R R R Enterococcus faecalis R R R R 1 R R R R 4.8 Enterococcus gallinarum, Enterococcus casseliflavus R R R R 1 R R R R R 4.9 Enterococcus faecium R R R R 1,2 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 R 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. EUCAST intrinsic resistance and exceptional phenotypes, Expert s version September 2016 Page 8 of 11

9 Table 5. Exceptional resistance phenotypes of Gram-negative bacteria Exceptional phenotypes Any Enterobacteriaceae (except Proteeae and 5.1 Serratia marcescens) Resistant to colistin 1,2 5.2 Salmonella Typhi Resistant to fluoroquinolones and/or carbapenems 5.3 Pseudomonas aeruginosa and Acinetobacter spp. Resistant to colistin 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 1 Except in countries where colistin resistance is not rare. 2 Colistin MICs for some Salmonella serotypes are slightly above the breakpoint (S 2; R >2 mg/l). EUCAST intrinsic resistance and exceptional phenotypes, Expert s version September 2016 Page 9 of 11

10 Table 6. Exceptional resistance phenotypes of Gram-positive bacteria Exceptional phenotypes Resistant to vancomycin, teicoplanin, telavancin, dalbavancin, oritavancin, daptomycin, 6.1 Staphylococcus aureus linezolid, tedizolid, quinupristin-dalfopristin and/or tigecycline. 6.2 Coagulase-negative staphylococci Resistant to vancomycin, telavancin, dalbavancin, oritavancin, daptomycin, linezolid 1, tedizolid 1, quinupristin-dalfopristin 1 and/or tigecycline. 6.3 Corynebacterium spp. Resistant to vancomycin, teicoplanin, telavancin, dalbavancin, oritavancin, daptomycin, 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 6.8 Enterococcus faecalis, Enterococcus gallinarum, Enterococcus casseliflavus, Enterococcus avium Susceptible to quinupristin-dalfopristin, consider misidentification. If also resistant to ampicillin it is almost certainly E. faecium. 1 Except in countries where linezolid, tedizolid or quinupristin-dalfopristin resistant coagulase-negative staphylococci are not rare. EUCAST intrinsic resistance and exceptional phenotypes, Expert s version September 2016 Page 10 of 11

11 Table 7. Exceptional resistance phenotypes of anaerobes Exceptional phenotypes 7.1 Bacteroides spp. Resistant to metronidazole 7.2 Clostridium difficile Resistant to metronidazole, vancomycin and/or fidaxomicin EUCAST intrinsic resistance and exceptional phenotypes, Expert s version September 2016 Page 11 of 11

Most common dose (mg) 1g x 1 1g x 1 1g x 1 1g x 1 1g x 1 1g x 1. Maximum dose schedule (mg) 1g x 1 1g x 1 1g x 1 1g x 1 1g x 1 1g x 1

Most common dose (mg) 1g x 1 1g x 1 1g x 1 1g x 1 1g x 1 1g x 1. Maximum dose schedule (mg) 1g x 1 1g x 1 1g x 1 1g x 1 1g x 1 1g x 1 Ertapenem Rationale for the EUCAST clinical breakpoints, version 1.3 1 st June 2009 Introduction Ertapenem is a carbapenem, available only for parenteral use. Ertapenem is relevant for therapy of septicaemia,