Transcript EUCAST 2003
EUCAST
European Committee on Antimicrobial Susceptibility Testing formed in 1997 and restructured in 2002 convened by European Society for Clinical Microbiology and Infectious Diseases (ESCMID) National Breakpoint Committees in Europe and financed by ESCMID National Breakpoint Committees in Europe DG-SANCO of the European Union (3 year grant from May 2004)
EUCAST - uppgifter
• Harmonisering av brytpunkter i Europa.
• Europeisk brytpunktskommitté för nya antibiotika.
• Europeiska brytpunkter för resistensövervakning inom humanmedicin, veterinärmedicin och livsmedelshantering.
• Verka för standardisering av metoder.
• Verka för extern kvalitetssäkring • Samverka med Europeiska nätverk och myndigheter inom området antibiotika, särskilt antibiotikaresistens (EMEA, ECDC, EARSS, m fl) • Rådge Europeiska myndigheter, professionella nätverk och industri • Samverka med motsvarande internationella grupper och kommitteer (CLSI, ESSTI, VetCast m fl)
EUCAST
EUCAST General Committee:
- one representative, appointed by the appropriate medical associations, from each European country - one representative each from ISC and FESCI - Chairperson and Scientific secretary (appointed by ESCMID) - meets once a year at ECCMID - all Steering Committee proposals are referred to the General Committee for comments before decision
EUCAST Steering Committee:
- Chairperson and a Scientific Secretary (appointed by ESCMID) - one representative each from the European national breakpoint committees (presently 6) - two representatives from the EUCAST General Committee - Czech Republic and Greece 2002-2004 - Russia and Spain 2004 -2006 - Italy and Poland 2006 - 2008
EUCAST industry email network
- Manufacturers of pharmaceuticals and susceptibility testing devices are invited to join the EUCAST network. Apply by contacting the chairman of EUCAST. - Steering Committee proposals are referred to the industry network for comments before decision
EUCAST General Committee 2006
Austria
Prof Helmut Mittermayer
Belgium
Prof Jan Verhaegen
Bosnia
Dr Selma Uzunovic-Kamberovic
Bulgaria
Prof Krassimir Metodiev
Croatia
Dr Arjana Tambic-Andrasevic
Czech Republic Denmark
Dr Pavla Urbaskova Dr Niels Frimodt Møller
Estonia
Dr Paul Naaber
Finland
Dr Antti Nissinen
France
Prof Claude-James Soussy
Germany
Prof Bernd Wiedemann
Greece
Prof Alkiviadis Vatopoulos
Hungary
Dr Éva Bán
Iceland
Dr Karl Gustaf Kristinsson
Ireland Italy
Dr Martin Cormican Prof Pietro Emanuele Varaldo
Latvia
Dr Arta Balode
Lithuania
Prof Arvydsa Ambrozaitis
Netherlands
Prof John Degener
Norway
Dr Martin Steinbakk
Poland
Prof Waleria Hryniewicz
Portugal
Prof Jose Melo Cristino
Romania
no official representative
Russia
Dr Olga Stetsiouk
Serbia
Dr Lazar Ranin
Slovak Republic
Prof. Milan Niks
Slovenia
Dr Jana Kolman
Spain
Dr Francisco Soriano
Sweden
Dr Barbro Olsson-Liljequist
Switzerland Turkey
Prof Jaques Bille Dr Deniz Gür
UK
Prof Alasdair MacGowan
Yugoslavia
no official representative
ISC
– Prof Paul Tulkens
FESCI
– Dr David Livermore
Email network of industry
with interest in antimicrobials
Chairperson
Gunnar Kahlmeter, Sweden
Scientific Secretary
Derek Brown, UK
EUCAST Steering Committee Membership
• •
Chairperson Scientific Secretary Gunnar Kahlmeter Derek Brown
• • • • • •
BSAC (The UK) CA-SFM (France) CRG (The Netherlands) DIN (Germany) NWGA (Norway) SRGA (Sweden) Alasdair MacGowan Fred Goldstein Johan W. Mouton Arne Rodloff Martin Steinbakk Anders Österlund
• •
General Committee rep Olga Stetsiouk (Russia) General Committee rep Francisco Soriano (Spain)
• •
General Committee rep Waleria Hryniewicz (Poland) General Committee rep Pietro Varaldo (Italy) 2005 - 08 2005 - 08 2005 - 08 2005 - 08 2005 - 08 2005 - 08 2005 - 08 2005 - 08 2004 - 06 2004 - 06 2006 - 08 2006 - 08
EUCAST Subkommittéer
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EUCAST svampkommitté (EUCAST AFST)
– Referensmetoder för resistensbestämning av svamp – Brytpunkter för svampmedel (flukonazole) med EUCASTs principiella processer
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EUCAST kommitté ”Expert Rules”
– Utvecklar gemensamma Europeiska expertregler
EUCAST websites are found at
www.eucast.org
The EUCAST websites are accessed via
www.eucast.org
This is a section of the official ESCMID website giving details of all EUCAST activities including - constitution - organisation - committee member lists - meetings - EUCAST documents - clinical MIC breakpoint tables - MIC distributions for wild type bacteria and fungi - epidemiological MIC cut-off values
www.eucast.org
This is the first screen of the EUCAST general website found at www.eucast.org
.
EUCAST definitions of clinical breakpoints
• •
Clinically Susceptible (S)
a microorganism is defined as susceptible if inhibited in-vitro by a concentration of an antimicrobial agent that is associated with a high likelihood of therapeutic success a microorganism is
categorized
defined phenotypic test system.
as susceptible (S) by applying the appropriate breakpoint in a • •
Clinically Intermediate (I)
a microorganism is defined as intermediate by a level of antimicrobial agent activity associated with uncertain therapeutic effect. - It implies that an infection due to the isolate may be appropriately treated in body sites where the
EUCAST has re-defined susceptible, intermediate and resistant and defined the terms ”wild type” and ”non-wild type”
a microorganism is
categorized
defined phenotypic test system
microorganism.
• •
The national breakpoint committees have also agreed on a common format for susceptible (S≤) and resistant (R>).
agent that is associated with a high likelihood of therapeutic failure a microorganism is
categorized
defined phenotypic test system.
as resistant (R) by applying the appropriate breakpoint in a
Clinical breakpoints may be altered with legitimate changes in circumstances Clinical breakpoints are presented as S
EUCAST definitions of epidemiological cut off values
• • •
Wild type (WT)
a microorganism is defined as wild type (WT) for a species by the absence of acquired and mutational resistance mechanisms to the drug in question.
a microorganism is categorized as wild type (WT) for a species by applying the appropriate cut-off value in a defined phenotypic test system.
wild type microorganisms may or may not respond clinically to antimicrobial treatment. • • •
Microbiological resistance - non-wild type (NWT)
a microorganism is defined as non-wild type (NWT) for a species by the presence of an acquired or mutational resistance mechanism to the drug in question. a microorganism is categorized as non-wild type (NWT) for a species by applying the appropriate cut-off value in a defined phenotypic test system.
non-wild type microorganisms may or may not respond clinically to antimicrobial treatment.
Epidemiological cut-off values will not be altered by changing circumstances.
The wild type is presented as WT
This is the first screen of the EUCAST program for the display of wild type MIC distributions in microorganisms. Choose to display in English, French or German. The link to the programme is found on www.eucast.org
www.eucast.org
Specify the drug or the bug (never both) - after a few seconds a table of MIC-distributions is shown. Click on any species in the left hand column to display the data as a bar chart, with EUCAST epidemiological cut-off values and harmonised European clinical breakpoints.
EUCAST vild typs MIC distributioner
• Referensmaterial för epidemiologiska brytpunkter för resistensövervakning • Referensmaterial för brytpunktskommittéer • MIC-uppslagsverk • Internationell referens för kalibrering av resistensbestämning
S.pneumoniae
vs ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin Ciprofloxacin 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0.002 0.004 0.008 0.016 0.032 0.064 0.125 0.25
0 0 0 0 0 0 1 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 1 1 1 2 80 5 4 197 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 6 3 0 2 0 0 0 0 0 4 0 1 0 0 1 1 3 2 4 2 3 3 0 16 8 20 5 13 22 9 13 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 8 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 13 0 0 0 0 0 0 0 6 0 0 0 0 0 0 0 0 0 0 0 0 9 0 0 0 0 0 0 0 7 0 0 0 0 1 0 3 0 0 2 0 4 8 1 0 0 0 0 0 0 25 8 0 2 1 1 8 20 0 1 3 0 4 4 0 0 0 1 0
0.5
28 55 45 2 256 64 35 251 125 96 92 161 245 225 426 402 75
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52 1191 363 15 61 155 130 41 102 209 69 544 854 917 933 1193 366
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16
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0
8 16 32 64 128 256 512
0 0 0 0 0 0 0 671 101 21 454 119 11 2 0 0 0 2 0 3 0 0 0 0 0 32 11 17 51 10 2 1 4 3 1 0 1 0 0 0 1 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 28 59 10 64 379 401 138 222 182 3 1 3 10 9 16 11 30 0 2 1 0 6 3 5 19 10 4 0 0 0 2 1 2 2 0 0 0 0 0 1 1 4 1 6 0 0 1 0 0 1 1 0 0 2 228 15 10 27 0 10 34 14 66 2 2 2 36 207 302 409 1052 1777 186 225 29 22 786 102 2 1 2 10 130 2195 10500 4618 144 67 10 47 176 95 21 1 1 0 2 6 103 7 4 37 335 100 35 60 58 265 130 16 11 26 51 1 0 5 3 0 1 0 0 0 0 1 0 0 280 122 120 155 50 181 77 120 85 49 99 331 111 544 256 210 272 31 11 28 78 18 149 74 76 96 2 1 3 2 4 23 6 1 1 2 1 2 2 9 18 8 1 0 4 0 0 0 0 0 0 1 2 0 1 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 2 1 41 65 99 150 55 18 11 4 1 0 0 1 0 0 0 422 2706 13072 3987 320 68 31 82 62 1 1 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 0 0 0 0 0 228 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Graph shown in the EUCAST program for display of MIC distributions of wild type bacteria.
V alues >1% show on graph!
(1) To define epidemiological cut-off values
(2) As a template for calibration of methodology (accuracy and imprecision).
”We have defined the result of antimicrobial susceptibility testing!”
(3) Reference MIC database for breakpoint setting - to avoid clinical breakpoints that divide wild type bacteria
(4) As MIC reference database
Examples from the EUCAST wild type MIC distribution program.
1
EUCAST procedure for setting breakpoints
The next 9 slides describe the EUCAST procedure for harmonising European breakpoints.
EUCAST procedure for setting breakpoints
1. Data on dosing, formulations, clinical indications and target organisms are reviewed and differences which might influence breakpoints are highlighted Dosage Most common dose Maximum dose schedule Available formulations BSAC UK CA-SFM France
500 x 2 oral 400 x 2 iv 500 x 2 oral 200 x 2 iv 750 x 2 oral 400 x 3 iv oral, iv 750 x 2 oral 400 x 3 iv oral, iv
CRG Netherlands
250 x 2 oral 200 x iv 750 x 2 oral 400 x 3 iv oral, iv
DIN Germany
500 x 2 oral 200 x 2 iv 750 x 2 oral 400 x 2 iv oral, iv
NWGA Norway
200-400 x 2 oral 400 x 2 iv data pending oral, iv
SRGA Sweden
500 x 2 oral 400 x 2 iv 750 x 2 oral 400 x 3 iv oral, iv
EUCAST procedure for setting breakpoints
2. Multiple MIC-distributions are collected, the wild type MIC distribution is defined and tentative epidemiological cut-off values determined (WT
EUCAST procedure for setting breakpoints
3. Existing national clinical breakpoints are compared Breakpoints prior to harmonisation (mg/L) S< R> General breakpoints Species related breakpoints
Enterobacteriaceae
Pseudomonas
spp.
Acinetobacter
spp.
Staphylococci Streptococci
S. pneumoniae
Enterococci
Haemophilus/Moraxella
spp.
Corynebacteria
N. Meningitidis N. Gonorrhoeae P. Multocida
Anaerobes
Campylobacter
spp.
Helicobacter pylori
BSAC ND 1/1 1/4 1/1 1/1 2/2 (I)* excluded 1/1 1/1 0.06/ ND excluded 1/1 2/2 CA-SFM 1/2 not yet excluded excluded excluded no CRG 1/2 0.06/1 no DIN 1/2 no NWGA 0.125/2 0.12/2 ND 0.12/2 0.12/2 0.12/2 (I)* 0.12/2 0.12/0.5
0.06/0.12
0.06/0.12
ND ND no SRGA 1/2 0.12/1 1/1 1/1 0.06/2 0.12/2 0.12/2 (I)* 0.12/2 0.12/0.25
excl 0.03/0.25
0.06/0.25
0.12/0.25
excluded no NCCLS 1/2 1/2 1/2 1/2 excl excl 1/2 1/ 0.06/0.5
4. Using available Pk/Pd data, Monte Carlo simulations are performed and a Pk/Pd breakpoint calculated based on conventional dosing regimens
200 180 160 140 120 100 80 60 40 20 0 0.25
ciprofloxacin 500 mg q12h oral 0.5
1 2
MIC mg/L
99% CI Average 4 8 S = 0.5 mg/L Pk/Pd 200 180 160 140 120 100 80 60 40 20 0 0.25
levofloxacin 500 mg q24h oral 0.5
1 2
MIC mg/L
99% CI Average 4 8 S = 1 mg/L
EUCAST procedure for setting breakpoints
5. Clinical data relating outcome to MIC-values, wild type and resistance mechanisms are assessed in relation to the tentative breakpoint
6a. Tentative breakpoints are checked against target species wild type MIC distributions to avoid splitting the wild type to obtain tentative breakpoints …the breakpoints were set at S≤0.125 and R>2 mg/L, rendering wild type S. pneumoniae intermediate in susceptibility to ciprofloxacin. Epidemiological cut off: WT<2.0
Splitting the wild type must be avoided to permit reproducible susceptibility testing
<2 mg/L
6b. Tentative breakpoints are checked against target species wild type MIC distributions to avoid splitting the wild type to obtain tentative breakpoints - example levofloxacin … a break-point of 2 mg/L was acceptable with a footnote that this relates to high dose therapy. Epidemiological cut off: WT<2.0
Splitting the wild type must be avoided to permit reproducible susceptibility testing!
<2 mg/L
EUCAST procedure for setting breakpoints
7. Tentative breakpoints proposed by the EUCAST Steering Committee are referred to the national breakpoint committees for comments.
When Steering Committee and national committees agree the tentative breakpoints are subjected to the EUCAST consultation process: 8. Consultation process on tentative breakpoints: - EUCAST General Committee - Expert groups (eg Neisseria, anaerobes) - Pharmaceutical industry, AST device manufacturers - Others via EUCAST website 9. Rationale document prepared and published on website
EUCAST breakpoint tables available at http://www.eucast.org
Click on name to directly access MIC distributions ”Dashed” – laboratories are recommended not to test against this species Insufficient evidence
Rationale documents
• The rationale for decisions on breakpoints (for new drugs or as a result of harmonising breakpoints for existing drugs) are made available as ”EUCAST rationale documents” on the EUCAST website.
An abbreviated version of the rationale documents will be published as ”EUCAST Technical Notes” in CMI, either on the drug in question (new drugs) or the class of drugs. The first which describes daptomycin will be published in 2006.
• The next slides shows a rationale document.
How to implement EUCAST breakpoints
• The national breakpoint committees have committed themselves to implementing EUCAST breakpoints breakpoint system.
– which means that anyone using either of the European national systems will gradually adhere to the European • Breakpoints as presented in EUCAST tables can be directly applied to MIC distributions (local and national surveillance, EARSS, etc) • • Systems for automated susceptibility testing can be set up with EUCAST MIC breakpoints (from 2007 at the earliest).
Through an agreement between EMEA, EUCAST and the pharmaceutical companies, new antimicrobials will be given breakpoints through EUCAST as part of the registration process. The SPC for these drugs will contain only EUCAST breakpoints.
EMEA SOP for setting breakpoints through EUCAST
Available from the EUCAST (www.eucast.org) and EMEA websites
•
EMEA SOP for setting breakpoints through EUCAST
Co-ordinated process between the Company, EMEA (rapporteurs and co-rapporteurs) and EUCAST • •
–
Where the Company applies for registration of a new agent
EMEA decides on indications – EUCAST decides on breakpoints.
EUCAST breakpoints for new drugs are included as the only breakpoints in the SPC (Summary of Product Characteristics).
Further EUCAST activities 2006/2007
• EUCAST workshop on ”The need for speciation in antimicrobial susceptibility testing” at ECCMID 2006 – 10.30-12.30 Sat 1st April 2006 – Calliope Room, International Conference Centre, Nice • EUCAST business meeting at ECCMID 2006 – 13.30-15.30 Sat 1st April 2006 – Calliope Room, International Conference Centre, Nice • EUCAST Symposium on ”Implications of low-level antimicrobial resistance” at ECCMID 2006 – 13.00-15.00 Tue 4th April 2006 – Hermes Room, International Conference Centre, Nice
EUCAST
The EUCAST presentation can be freely downloaded from the www.eucast.org to be used by anyone wanting to present EUCAST to colleagues, students, committees, administrations etc. Comments and suggestions are invited: [email protected]