Penicillins - EUCAST clinical MIC breakpoints (version 1.3)

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1 EUCAST clinical MIC breakpoints - penicillins Penicillins - EUCAST clinical MIC breakpoints (version 1.3) Penicillins Click on antibiotic name to see wild type MIC distributions. Enterobacteriaceae A Pseudomonas B Acinetobacter C Staphylococcus D Entero- E coccus Streptococcus A, B,C,G F S.pneu- H.influmoniae G enzae I Other streptococci H M.catarrhalis J N. gonorrhoeae K N.meningitidis Gramnegative L Grampositive Non-species breakpoints M Benzylpenicillin RD /0.12 Note E 0.25/ /20.25/2 IE /1 0.06/0.25/ / /2 Ampicillin N RD Note A / Note D 4/8 Note F 0.5/20.5/2 1/1 1/1 Note K 0.12/1 0.5/2 4/8 2/8 O Ampicillin/sulbactam RD Note A /8 -- IE Note D 4/8 Note F Note G Note H 1/1 1/1 IE IE 4/8 4/8 2/8 Amoxicillin RD Note A / Note D 4/8 Note F Note G 0.5/2 1/1 1/1 Note K (0.12/1) 0.5/2 4/8 2/8 Amoxicillin/clavulanateO RD Note A / Note D 4/8 Note F Note G Note H 1/1 1/1 Note K -- 4/8 4/8 2/8 Piperacillin RD 8/16 16/16 IE Note D Note E Note F Note G Note H Note I Note J /16 8/16 4/16 Piperacillin/tazobactamO RD 8/16 16/16 IE Note D Note E Note F Note G Note Note I Note J /16 8/16 4/16 Ticarcillin RD 8/16 16/16 IE Note D Note E IE IE IE /16 8/16 8/16 Ticarcillin/clavulanate O RD 8/16 16/16 IE Note D Note E IE IE IE /16 8/16 8/16 Phenoxymethylpenicillin RD Note D -- Note F Note G IE IE IE IE IE Mecillinam P RD 8/ IE Oxacillin RD Note D -- Note F IE Cloxacillin RD Note D -- Note F IE Dicloxacillin RD Note D -- Note F IE Flucloxacillin RD Note D -- Note F IE A. Enterobacteriaceae: and aminopenicillin breakpoints: The resistant breakpoint of R>8 mg/l ensures that all isolates with resistance mechanisms are reported resistant. The wide range of dosages and intravenous vs. oral administration significantly affect therapeutic efficacy. The unspecified S breakpoint enables the user to categorise wild type Escherichia coli and Proteus mirabilis S or I to the aminopenicillins. This will depend on dosing, route of administration and on whether the infection is systemic or affects the urinary tract only. B. Pseudomonas aeruginosa: Piperacillin and ticarcillin breakpoints for Pseudomonas spp. are based on high dose therapy (for piperacillin with or without tazobactam 4 g x 4 and for ticarcillin with or without clavulanate 3 g x 4). The susceptible breakpoints were increased to avoid dividing wild type MIC distributions. C. Acinetobacter: Susceptibility testing of Acinetobacter spp. to penicillins is unreliable. In most instances Acinetobacter spp. are resistant to penicillins. D. Staphylococci: Most staphylococci are penicillinase-producers. Penicillinase-producing strains are resistant to benzylpenicillin, phenoxymethylpenicillin, amino-, carboxy- and ureidopenicillins. The benzylpenicillin breakpoint will mostly, but not unequivocally, separate beta-lactamase producers from non-producers. S. aureus and S. lugdunensis with oxacillin MIC values >2 mg/l and/or cefoxitin MIC values >4 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 whereas cefoxitin is a poorer predictor of methicillin resistance in CNS. E. Enterococci: Refer to national or international endocarditis guidelines for breakpoints for Enterococcus spp. in endocarditis. Ampicillin and amoxicillin are considered active against wild type enterococci. E. faecalis susceptible to ampicillin (or amoxicillin) can be categorised as susceptible to piperacillin (with or without tazobactam). E. faecium resistant to penicillins can be considered resistant to all other beta-lactam drugs including carbapenems. Enterococci are intrinsically resistant to ticarcillin with or without clavulanate. F. Streptococci: The beta-lactam susceptibility of beta-haemolytic streptococci groups A, B, C and G is inferred from the penicillin susceptibility. 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 sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC above the current resistant breakpoint (in italics) they should be reported resistant. Streptococci groups A, B, C and G do not produce beta-lactamase. The addition of a beta-lactamase inhibitor does not add clinical benefit. G. Streptococcus pneumoniae: 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 susceptible to benzylpenicillin can be reported susceptible to these and other relevant beta-lactam antibiotics. In pneumonia, strains with with MIC 0.5 mg/l should be regarded as susceptible to benzylpenicillin at doses of at least 1.2 g x 4, with MIC 1 mg/l at doses of 2.4 g x 4 or 1.2 g x 6 and strains with MIC 2.0 mg/l susceptible at doses of 2.4 g x 6. In meningitis, isolates with MICs above 0.06 mg/l should be categorised resistant to penicillin. For benzylpenicillin and other indications, use breakpoints of 0.06/2 mg/l for categorisation. For ampicillin, amoxicillin and piperacillin, irrespective of the presence or absence of an inhibitor, categorise using the ampicillin test result. For phenoxymethylpenicillin, report S. pneumoniae with benzylpenicillin MICs above 0.06 mg/l resistant. H. Viridans streptococci: In endocarditis, refer to national or international endocarditis guidelines for breakpoints for viridans streptococci. I. Haemophilus influenzae: Always test for beta-lactamase and report positive strains resistant to penicillins without beta-lactamase inhibitors. Breakpoints relate only to beta-lactamase negative strains. Strains may be resistant to penicillins, aminopenicillins and/or cefalosporins due to changes in PBPs (BLNAR, Betalactamase negative ampicillin resistant) and a few strains have both resistance mechanisms (BLPACR, betalactamase positive amoxicillin/clavulanate resistant). Isolates susceptible to ampicillin and amoxicillin are also (1 / 2) 오전 9:09:48

2 EUCAST clinical MIC breakpoints - penicillins susceptible to piperacillin and piperacillin/tazobactam and isolates susceptible to amoxicillin/clavulanate to piperacillin/tazobactam. J. Moraxella catarrhalis: Can be reported resistant to penicillins and aminopenicillins without inhibitors since >85% of the isolates produce beta-lactamase. K. Neisseria gonorrhoeae: Should always be tested 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. L. Gram-negative : Susceptibility to ampicillin, amoxicillin and piperacillin without beta-lactamase inhibitors can be inferred from their susceptibility to benzylpenicillin. M. Non-species breakpoints have been determined mainly on the basis of PK/PD data and are independent of MIC distributions of specific species. They are for use only for species not mentioned in the table or footnotes. N. Ampicillin is used in the treatment of Listeria monocytogenes (MIC values 2 mg/l for wild type organisms). O. For susceptibility testing purposes, the concentration of clavulanate is fixed at 2 mg/l and of sulbactam and tazobactam at 4 mg/l. P. Mecillinam breakpoints apply to uncomplicated, lower urinary tract infections only. -- = Susceptibility testing not recommended as the species is a poor target for therapy with the drug RD = Rationale document with data used by EUCAST for determining breakpoints Links from antibiotic names to MIC-distributions introduced for antibiotics with available data Correction of error in the numbering of footnotes (N and O had been erroneously switched). The A-, G- and H-footnotes have been revised A series of formatting and mistakes have been corrected. Former footnote Q was included in H and mecillinam footnote was changed from Q to P EUCAST breakpoints for penicillins decided on April 23, The breakpoints will be reviewed after 18 months. Comments are invited. (2 / 2) 오전 9:09:48

3 Cephalosporins for oral use - EU Cephalosporins - EUCAST clinical MIC breakpoints (v 2.0) Click on antibiotic name for wild type MIC distributions. Click on RD for rationale document. Intravenous cephalosporins Enterobac- Pseudomonas teriaceae B Acinetobacter Staphylococcus Enterococcucoccumoniae Strepto- S.pneu- A,B,C,G Nonspecies breakpoints A Cefazolin RD Note F - Note H - 0.5/ /2 Cefepime RD 1/8 8/8 E - Note F - Note H 1/2 0.5/ / / /8 Cefotaxime RD 1/2 - - Note F - Note H 0.5/2 0.5/ /0.12 1/2 0.12/ / /2 Ceftazidime RD 1/8 8/8 E /8 Ceftriaxone RD 1/2 - - Note F - Note H 0.5/2 0.5/ /0.12 1/2 0.12/ / /2 Cefuroxime RD 8/8 C - - Note F - Note H 0.5/1 0.5/0.5 1/2 1/ /8 Oral cephalosporins Cefaclor RD Note F,G - Note H 0.03/ / / IE Cefadroxil RD D 16/ Note F - Note H IE Cefalexin RD D 16/ Note F - Note H IE Cefixime RD 1/1 D / /1 0.12/0.12 I IE Cefpodoxime RD 1/1 D - - Note F - Note H 0.25/ / /0.5 IE IE Ceftibuten RD 1/1 D - - IE - Note H IE - 1/1 1/1 IE IE Other streptococci H.influenzae M.catarrhalis N.gonorrhoeae N.meningitidis Grampositive Gramnegative Cefuroximeaxetil RD 8/8 D - - Note F - Note H 0.25/ /1 0.12/ IE A. Non-species breakpoints have been determined mainly on the basis of Pk/Pd data and are independent of MIC distributions of specific species. They are for use only for species not mentioned in the table or footnotes. (1 / 2) 오전 9:10:26

4 Cephalosporins for oral use - EU B. The cephalosporin breakpoints for Enterobacteriaceae will detect reduced susceptibility mediated by most clinically important beta-lactamases in Enterobacteriaceae. Occasional ESBL-producing strains will be reported susceptible. For purposes of infection control, epidemiology and surveillance, laboratories may wish to use specific tests to screen for and confirm ESBL-production. C. For cefuroxime, the breakpoints relate to a dosage of 1.5 g x 3 and to Escherichia coli, Proteus mirabilis and Klebsiella spp. only. D. For uncomplicated urinary tract infections only. E. For cefepime and ceftazidime the susceptible breakpoint for Pseudomonas aeruginosa has been increased to avoid dividing the MIC wild type distribution. The breakpoints relate to high dosage, i.e. 2 g x 3 for both cefepime and ceftazidime. F. Susceptibility of staphylococci to cephalosporins is inferred from the methicillin susceptibility. G. For cefaclor, high-dose therapy is required for treatment of staphylococcal infections. H. The susceptibility of streptococcus groups A, B, C and G can be inferred from their susceptibility to benzylpenicillin. I. 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. - = Susceptibility testing not recommended as the species is a poor target for therapy with the drug. RD = rationale document listing data used by EUCAST for determining breakpoints Released by EUCAST - oral cephalosporins Released by EUCAST - parenteral cephalosporins. (2 / 2) 오전 9:10:26

5 EUCAST clinical MIC breakpoints - carbapenems Carbapenems - EUCAST clinical MIC breakpoints (v 3.1) Carbapenem Click on antibiotic name to see wild type MIC distributions Enterobacteriaceae Pseudomonas Acineto-bacter Doripenem RD 1/4 1/4 1/4 Ertapenem RD 0.5/ Imipenem RD 2/8 B 4/8 C 2/8 Meropenem RD 2/8 2/8 2/8 Staphylococcus Enterococcus Strepto- S.pneu- Other streptococcus moniae cocci A,B,C,G H.influenzae M.catarrhalis N.gonorrhoeae N.meningitidis Gramnegative Grampositive Non-species breakpoints A note D -- 1/1 E 1/1 E, F 1/1 E 1/1 E, F IE IE 1/1 1/1 1/4 note D /0.5 E 0.5/0.5 E,F 0.5/0.5 E 0.5/0.5 E, F IE -- 1/1 H 1/1 H 0.5/1 note D C 4/8 2/2 E 2/2 E, F 2/2 E 2/2 E, F IE -- 2/8 2/8 2/8 note D -- 2/2 E 2/2 E 2/2 E 2/2 E,F IE 0.25/0.25 E,G 2/8 2/8 2/8 A. Non-species breakpoints have been determined mainly on the basis of PK/PD data and are independent of MIC distributions of specific species. They are for use only for species not mentioned in the table or footnotes. B. Proteus and Morganella species are considered poor targets for imipenem. C. The imipenem S/I breakpoint for Pseudomonas and Enterococcus was increased from 2 to 4 mg/l to avoid dividing the wild type MIC distribution. The breakpoints for Pseudomonas relate to high dose frequent therapy. D. Susceptibility of staphylococci to carbapenems is inferred from the methicillin susceptibility. E. Strains with MIC values above the S/I breakpoint are 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 (in italics) they should be reported resistant. F. Only meropenem is used for meningitis. In meningitis, meropenem breakpoints for Streptococcus pneumoniae and Haemophilus influenzae are 0.25/1 mg/l. G. Meropenem breakpoints for Neisseria meningititis relate to meningitis only. H. The ertapenem S/I breakpoint for was moved from 0.5 to 1.0 to avoid dividing wild type MIC distributions. RD =Rationale document listing data used for setting EUCAST breakpoints Rationale documents published - click on RD "Other streptococci" breakpoints added to table Doripenem added to table following EMEA positive opinion. "Other streptococci" breakpoints pending) added to table This table rearranged in reverse chronological order Released by EUCAST 오전 9:14:03

6 EUCAST clinical MIC breakpoints - aztreonam Monobactams - EUCAST clinical MIC breakpoints (v 1.3) Aztreonam Click on antibiotic name to see wild type MIC distributions Enterobacteriaceae B Pseudomonas Acinetobacter Staphylococcus Enterococcus Streptococcus A, B,C,G S.pneu- Other strepto- H.influenzae moniae cocci M.catarrhalis N.gonorrhoeae N.meningitidis Gram-positive Gram-negative Non-species breakpoints A Aztreonam RD 1/8 1/16 C IE IE /8 A. Non-species breakpoints have been determined mainly on the basis of PK/PD data and are independent of MIC distributions of specific species. They are for use only for species not mentioned in the table or footnotes. B. The aztreonam breakpoints for Enterobacteriaceae will detect resistance mediated by most ESBLs and other clinically important beta-lactamases in Enterobacteriaceae. However, some strains that produce ESBLs appear susceptible or intermediate with these breakpoints. Laboratories may want to use a test which specifically screens for the presence of ESBL. C. The I/R-breakpoint for aztreonam in Pseudomonas aeruginosa was increased to avoid dividing the MIC wild type distribution. The I/R-breakpoint relates to high dose therapy. RD = rationale document listing data used by EUCAST for determining breakpoints "Other streptococci" and "Grampositive " added This table rearranged in reversed chronological order Footnote 2, amended to include intermediate Released by EUCAST 오전 9:14:30

7 EUCAST clinical MIC breakpoints - fluoroquinolones Fluoroquinolones - EUCAST clinical MIC breakpoints (v 2.6) Fluoroquinolone B Click on antibiotic name to see wild type MIC distributions Enterobacteriaceae C Staphylococcus Pseudomonas/ Acinetobacter Non-species Entero- Strepto- S.pneu- Other H.influenzae N.gonorr- N.menin- Gram- Gramnegative A coccus coccus breakpoints moniae F strepto- M.catarrhalis hoeae H positive A,B,C,G cocci gitidis Ciprofloxacin RD 0.5/1 0.5/1 1/1 D 1/1 E / /0.5 G 0.03/ / /1 Levofloxacin RD 1/2 1/2 1/2 1/2 -- 1/2 2/2 IE 1/1 G IE IE /2 Moxifloxacin RD 0.5/ / /1 0.5/0.5 IE 0.5/0.5 G IE IE IE IE 0.5/1 Norfloxacin RD 0.5/ IE /1 Ofloxacin RD 0.5/ /1 E / /0.5 G 0.12/0.25 IE /1 A. Non-species breakpoints have been determined mainly on the basis of PK/PD data and are independent of MIC distributions of specific species. They are for use only for species not mentioned in the table or footnotes B. For breakpoints for other fluoroquinolones (eg. pefloxacin and enoxacin) - refer to breakpoints determined by national breakpoint committees. C. 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. D. The S/I breakpoint has been increased from 0.5 to1 mg/l to avoid dividing the wild type MIC distribution. Thus there is no intermediate category for Acinetobacter species E. Staphylococcus spp - breakpoints for ciprofloxacin and ofloxacin relate to high dose therapy. F. Streptococcus pneumoniae - wild type S.pneumoniae are not considered susceptible to ciprofloxacin or ofloxacin and are therefore categorized as intermediate. For ofloxacin the I/R breakpoint was increased from 1.0 to 4.0 mg/l and for levofloxacin the S/Ibreakpoint from 1.0 to 2.0 to avoid dividing the wild type MIC distribution. The breakpoints for levofloxacin relate to high dose therapy. G. 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 sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC above the current resistant breakpoint (in italics) they should be reported resistant. Haemophilus/Moraxella - fluoroquinolone low-level resistance (ciprofloxacin MIC:s of mg/l) may occur in H. influenzae. There is no evidence that low-level resistance is of clinical importance in respiratory tract infections with H.influenzae. H. Neisseria meningitidis - breakpoints apply to the use of ciprofloxacin in the prophylaxis of meningococcal disease. RD =Rationale document listing data used for setting EUCAST breakpoints Clerical error in the numbering of footnotes corrected "Other streptococci" and "Grampositive " added to table. No new breakpoints added Error correction (wrong footnote for S.pneumoniae - changed from 5 to 6) Links to EUCAST Rationale Documents added This table rearranged in reverse chronological order Added an explanation of links from antibiotic names to wild type MIC distributions. Revised footnotes. Table version number added. (1 / 2) 오전 9:14:52

8 EUCAST clinical MIC breakpoints - fluoroquinolones Moxifloxacin given breakpoints for staphylococci and streptococci European fluoroquinolone breakpoints harmonised by EUCAST (2 / 2) 오전 9:14:52

9 EUCAST clinical MIC breakpoints - aminoglycosides Aminoglycosides - EUCAST clinical MIC breakpoints (v 1.5) Aminoglycosides B Click on antibiotic name to see wild type MIC distributions. Enterobacteriaceae Pseudomonas C Acinetobacter C Staphylococcus Enterococcus D Streptococcus A,B, C,G S.pneumoniae Other streptococci H.influenzae M.catarrhalis N.gonorrhoeae N.meningitidis Grampositive Gramnegative Non-species breakpoints A Amikacin RD 8/16 8/16 8/16 8/16 E IE /16 Gentamicin RD 2/4 4/4 4/4 1/ IE /4 Netilmicin RD 2/4 4/4 4/4 1/ IE /4 Tobramycin RD 2/4 4/4 4/4 1/ IE /4 A. Non-species breakpoints have been determined mainly on the basis of PK/PD data and are independent of MIC distributions of specific species. They are for use only for species not mentioned in the table or footnotes. B. The aminoglycoside breakpoints are based on modern once-daily administration of high aminoglycoside dosages. Most often aminoglycosides are given in combination with beta-lactam agents. For unlisted aminoglycosides refer to breakpoints determined by national breakpoint committees. C. The S/I breakpoint has been increased from 2 to 4 mg/l for agents other than amikacin to avoid dividing the wild type MIC distribution. Thus there is no intermediate category for Pseudomonas species and Acinetobacter species. D. Enterococcus spp - aminoglycoside monotherapy is ineffective against enterococci. There is synergism between aminoglycosides and betalactams in enterococci without acquired resistance mechanisms. There is no synergistic effect in enterococci with high level aminoglycoside resistance, i.e with gentamicin MIC>128 mg/l. E. Resistance to amikacin and kanamycin is most reliably determined using kanamycin as test substance. RD =Rationale document listing data used for setting EUCAST breakpoints Rationale Documents published "Other streptococci" and "Grampositive " added to table The table sorted in reversed chronological order Added an explanation of links from antibiotic names to wild type MIC distributions. Revised footnotes. Table version number added European aminoglycoside breakpoints harmonised by EUCAST. 오전 9:15:15

10 EUCAST clinical MIC breakpoints - glycopeptides Glycopeptides - EUCAST clinical MIC breakpoints (v 1.3) Glycopeptides Click on antibiotic name to see wild type MIC distributions. Enterobacteriaceae Pseudomonas Acinetobacter Staphylococcus 2 Non-species Entero- S.pneu- H.influenzae N.gonorr- N.meningbreakpoints 1 coccus moniae M.catarrhalis hoeae itidis Streptococcus A,B,C, G Other streptococci Grampositive Gramnegative Vancomycin RD /8 2 4/8 4/4 3 4/4 3 4/ /8 -- 4/8 Teicoplanin RD /8 2 4/8 4/4 3 4/4 3 4/ /8 1. Non-species breakpoints have been determined mainly on the basis of PK/PD data and are independent of MIC distributions of specific species. They are for use only for species that have not been given a species-specific breakpoint and not for those species where susceptibility testing is not recommended (marked with -- or IE in the table). 2. Staphylococcus aureus may be categorized as falsely susceptible to glycopeptides as glycopeptide MICs for strains with reduced susceptibility are dependant on the test conditions, in particular the medium used. 3. 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 sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC above the current resistant breakpoint (in italics) they should be reported resistant. RD = Rationale document listing data used for setting EUCAST breakpoints This table rearranged in reverse chronological order Added an explanation of links from antibiotic names to wild type MIC distributions. Revised footnotes. Table version number added European glycopeptide breakpoints harmonised by EUCAST 오전 9:16:09

11 EUCAST clinical MIC breakpoints - macrolides Macrolides, lincosamides, streptogramins - EUCAST clinical MIC breakpoints (v 1.4) MLS antimicrobials Click on antibiotic name to see wild type MIC distributions Enterobac- Pseudomonabactercoccuscoccus Acineto- Staphylo- Entero- Strepto- S.pneu- Other strepto- H.influ-enzae M.catarr- N. N. Gram- coccus moniae A, teriaceae cocci halisgonorr- mening- negative B,C,G hoeae itidis Azithromycin B RD D / / /0.5 IE 0.12/4 Gram-positive Non-species breakpoints A 0.5/ / IE Clarithromycin B,C RD / / /0.5 IE 1/32 D 0.25/ IE Erythromycin B RD D / / /0.5 IE 0.5/ / IE IE IE Roxithromycin B RD / /1 0.5/1 IE 1/16 D 0.5/ IE Telithromycin RD D IE / /0.5 IE 0.12/8 0.25/ IE Clindamycin RD E / E E E 0.5/ / / /4 4/4 IE Quinupristin/dalfopristin RD F /2 1/ IE IE A. Non-species breakpoints have been determined mainly on ns the of basis specific of PK/PD species. data They and are for independent use only of for MIC species distributio not men pharmacodynamic data for calculation of macrolide, lincosamines and t, hence streptogramins IE. non-species breakpoints are not robus B. Erythromycin can be used to determine the susceptibility of hromycin the listed and bacteria roxithromycin). to the other Macrolides macrolides administered Legionella (azithromycin, intravenously pneumophila (erythromycin clarit a MIC 1 mg/l for wild type isolates). Macrolides have Campylobacter been used (erythromycin jejuni the treatment MIC 4 of mg/l infections for wild with type isolates). Azithromycin S. typhi (MIC has be 16 mg/l for wild type Shigella isolates) spp. and C. Clarithromycin is used H. for pylori (MIC the 0.25 eradication mg/l for of wild type isolates). D. The correlation H. influenzae between macrolide MICs and clinical outcome is weak. Therefore, breakpoints se wild for H. type influenzae macrolides as intermediate. and antibiotics we E. Inducible clindamycin resistance can only be detected in the presence of a macrolide antibiotic. F. Quinopristin/dalfopristin E. faecium breakpoints only. are valid for RD = Rationale document with data used by EUCAST for determining breakpoints. NA = Not applicable Breakpoints for "other streptococci" included in table Error correction - in columns "Streptococcus" and "S.pneumoniae" there was an erroneus reference to footnote 5 - corrected to "footnote E" "Other streptococci" added to table Shigella spp added to footnote Macrolide breakpoints harmonised by EUCAST. (1 / 2) 오전 9:16:41

12 EUCAST clinical MIC breakpoints - tigecycline Tetracyclines - EUCAST clinical MIC breakpoints (v 2.2) Tetracyclines Click on antibiotic name to see wild type MIC distributions and on RD to see ratinale document. Strepto- Other Grampositivnegative Gram- Enterobac- Pseudomonabactecoccus coccus moniae M.catarrhalis hoeae itidis Acineto- Staphylo- Entero- S.pneu- H.influenzae N.gonorr- N.mening- coccus A, streptococci teriaceae B,C,G Doxycycline B RD /2 -- 1/2 1/2 -- 1/2 IE -- Note H Note H IE Minocycline B RD IE 0.5/ /1 0.5/1 -- 1/2 0.5/1 1/2 Note H Note H IE Tetracycline C RD /2 -- 1/2 1/2 -- 1/2 0.5/1 1/2 D Note H Note H IE Tigecycline RD Non-species breakpoints A 1/2 E -- IE 0.5/0.5 F,G 0.25/0.5 G 0.25/0.5 G IE IE IE IE IE Note H Note H 0.25/0.5 A. Non-species breakpoints have been determined mainly on the basis of PK/PD data and are independent of MIC distributions of specific species. They are for use only for species not mentioned in the table or footnotes B. Microorganisms susceptible to tetracycline are also susceptible to doxycycline and minocycline. Some staphylococci, streptococci and H. influenzae resistant to tetracycline may be susceptible to minocycline and/or doxycycline. C. Tetracycline breakpoints for Pasteurella multocida are 2/4 mg/l. Tetracyclines are used in the treatment of brucellosis (wild type Brucella mellitensis MIC <1 mg/l), and infections with Yersinia pestis (wild type MIC <4 mg/l), Yersinia enterocolitica (wild type MIC <4 mg/l), Burkholderia pseudomallei (wild type MIC <16 mg/l) and Leptospira spp. (wild type MIC <4 mg/l). Tetracyclines are active against Mycoplasma pneumoniae, Chlamydia, Rickettsia, Coxiella, Borrelia and Treponema spp. but susceptibility testing is rarely performed. Tetracyclines have been used in exceptional cases of urinary tract infections caused by multi-resistant Pseudomonas aeruginosa. D Tetracycline can be used to determine minocycline susceptibility for prophylaxis of Neisseria meningitidis infections. E. The S/I and I/R breakpoints were increased to avoid dividing wild type MIC distributions of relevant species. Tigecycline has decreased activity against Morganella spp., Proteus spp. and Providencia spp. F. The S/I breakpoint was increased to avoid dividing wild type MIC distributions of relevant species. G. 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 sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC above the current resistant breakpoint (in italics) they should be reported resistant. H. 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 breakpoint for susceptibility testing is given. RD = Rationale document listing data used for setting EUCAST breakpoints "Other streptococci" added to table. No new breakpoints added Error corrections not involving actual breakpoints Tetracycline EUCAST breakpoints published on EUCAST website. Tetracycline breakpoints added to tigecycline breakpoint table (v1.0) Tigecycline EUCAST clinical MIC breakpoints made available on the EUCAST website. 오전 9:17:45

13 EUCAST clinical breakpoints Miscellaneous antimicrobials - EUCAST clinical MIC breakpoints (v 2.2) Antimicrobial Enterococcus Enterobacteriaceae Pseudomonas Acinetobacter Staphylococcus Streptococcus S.pneumoniae A,B,C,G H.influenzae M.catarrhalis Grampositive Gramnegative Chloramphenicol RD 8/ /8 -- 8/8 8/8 -- 1/2 -- 2/4 8/8 8/8 IE Colistin RD 2/2 2/2 2/ IE Daptomycin RD /1 B IE 1/1 B IE IE Non-species breakpoints A Other streptococci N.gonorrhoeae N.meningitidis Fosfomycin iv RD 32/32 32/32 C -- 32/ IE -- IE IE Fosfomycintrometamol RD 32/ IE Fusidic acid RD /1 -- IE IE Linezolid RD /4 E 4/4 E 2/4 4/ /4 Metronidazole F RD /4 4/4 -- Nitrofurantoin D RD 64/ /64 64/64 64/ IE Rifampicin RD / / / / /0.25G IE Spectinomycin RD / IE Trimethoprim D RD 2/ / /1 H IE Trimethoprimsulfamethoxazole -- RD 2/4 S.malto- 2/4 2/ /1 H 1/2 1/ / IE (co-trimoxazole) I philia:4/4 A. Non-species breakpoints have been determined mainly on the basis of PK/PD data and are independent of MIC distributions of specific species. They are for use only for species not mentioned in the table or footnotes. B. 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 sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC above the current resistant breakpoint (in italics) they should be reported resistant. C. Intravenous fosfomycin may be used in combination with other drugs to treat Pseudomonas aeruginosa infections. D. For urinary tract infections only. E. The S/I breakpoint was increased to avoid dividing wild type MIC distributions of relevant species. F. Metronidazole is used in the treatment of Helicobacter pylori infections (wild type MICs 4 mg/l): breakpoints are 4/4 mg/l. G. For prophylaxis of bacterial meningitis only (refer to national guidelines). H. The activity of trimethoprim is uncertain against enterococci. Hence the wild type population is categorized as intermediate. I. Trimethoprim:sulfamethoxazole in the ratio 1:19. Breakpoints are expressed as the trimethoprim concentration. 0.5/2 = breakpoints S< 0.5 mg/l and R> 2 mg/l. IE = There is insufficient evidence that the species in question is a good target for therapy with the drug "Other streptococci" added to table Error corrections (format, style, spelling) not involving actual breakpoints Breakpoints for miscellaneous antimicrobials finalised by EUCAST Daptomycin breakpoints finalised by EUCAST (1 / 2) 오전 9:18:15

14 EUCAST clinical breakpoints Linezolid breakpoints harmonised by EUCAST. EUCAST 2003 (The European Committee on Antimicrobial Susceptibility Testing) Updated , G Kahlmeter (2 / 2) 오전 9:18:15

15 EUCAST clinical MIC breakpoints - Antimicrobials for Candida Antimicrobials for Candida infections - EUCAST clinical MIC breakpoints (v 2.0) Antifungal Click on antimicrobial name to see wild type MIC distributions Candida albicans Candida glabrata Candida krusei Non-species Candida parapsilosis Candida tropicalis breakpoints A Fluconazole RD 2/4 IE -- 2/4 2/4 2/4 Voriconazole RD 0.125/0.125 B IE /0.125 B 0.125/0.125 B IE A. Non-species breakpoints have been determined mainly on the basis of PK/PD data and are independent of MIC distributions of specific species. They are for use only for organisms that do not have specific breakpoints. B. Strains with MIC values above the S/I breakpoint are 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 (in italics) they should be reported resistant. RD =Rationale document listing data used for setting EUCAST breakpoints Voriconazole Rationale Document by the EUCAST Subcommittee on Antifungal Susceptiubility Testing (EUCAST AFST) published on EUCAST website Voriconazole breakpoints as determined by the EUCAST Subcommittee on Antifungal Susceptiubility Testing (EUCAST AFST) made publicly available Fluconazole breakpoints as determined by the EUCAST Subcommittee on Antifungal Susceptiubility Testing (EUCAST AFST) made publicly available 오전 9:18:45

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