Transcript EUCAST 2003

Antimicrobial susceptibility testing in Europe
- the role of national breakpoint committees and EUCAST
Gunnar Kahlmeter, EUCAST
[email protected]
NCCLS (USA)
BSAC wp
DIN
CA-SFM
CRG
NWGA
SRGA
E.coli vs. cefotaxim
S< / R>
R (%)
2/2
1.8 %
4 / 32
0.6 %
CRG
4/8
0.9 %
DIN
2/8
1.1 %
NCCLS
8 / 32
0.6 %
NWGA
1/2
1.8 %
SRGA
0.5 / 1
2.6 %
ND
-
(WT< 0.5)
5.0 %
BSAC
CA-SFM
EUCAST tentative
clinical brpt
EUCAST
epidemiological cut off
E.coli vs. cefotaxim
S< / R>
R (%)
2/2
1.8 %
4 / 32
0.6 %
CRG
4/8
0.9 %
DIN
2/8
1.1 %
NCCLS
8 / 32
0.6 %
NWGA
1/2
1.8 %
SRGA
0.5 / 1
2.6 %
ND
-
(WT< 0.5)
5.0 %
BSAC
CA-SFM
EUCAST tentative
clinical brpt
EUCAST
epidemiological cut off
E.coli vs. Cefotaxime in EARSS 2002
Austria, Germany, Sweden
300
Simulated local outbreak!
250
200
150
100
50
256
128
64
32
16
8
4
2
1
0,5
0,25
0,13
0,06
0,03
0,02
0,01
0
0
The breakpoint compromise!
Clinical aspects
– breakpoints must have clinical value!
Epidemiological aspects
– breakpoints must allow (early) detection of acquired resistance mechanisms!
Methodological aspects
– breakpoints must allow reproducible S-, I- and R-categorization in the lab!
<2.0
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
•
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
•
EUCAST industry network
- The network consists of all interested manufacturers of pharmaceuticals and
susceptibility testing devices. All are invited to take an active part in EUCAST activities
- Steering Committee proposals are referred to the industry network for comments before
decision
- relevant industry members can apply for inclusion on the email list by contacting the
EUCAST secretariat
EUCAST General Committee 2004
Austria Prof Helmut Mittermayer
Belgium Prof Jan Verhaegen
Bosnia Dr Selma Uzunovic-Kamberovic
Bulgaria Prof Krassimir Metodiev
Croatia Dr Arjana Tambic-Andrasevic
Czech Republic Dr Pavla Urbaskova
Denmark 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
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 Prof Jaques Bille
Turkey Dr Deniz Gür
Ireland Dr Martin Cormican
ISC – Prof Paul Tulkens
Italy Prof Pietro Emanuele Varaldo
Latvia Dr Arta Balode
Lithuania Prof Arvydsa Ambrozaitis
Netherlands Prof John Degener
Norway Dr Martin Steinbakk
Poland Prof Waleria Hryniewicz
FESCI – Prof David Livermore
UK Prof Alasdair MacGowan
Yugoslavia no official representative
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
2002 - 05
2002 - 05
• 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
2002 - 05
2002 - 05
2002 - 05
2002 - 05
2002 - 05
2002 - 05
• General Committee rep Olga Stetsiouk (Russia)
• General Committee rep Francisco Soriano (Spain)
2004 - 06
2004 - 06
EUCAST definitions of clinical breakpoints
available at www.eucast.org
Clinically Susceptible (S)
• a microorganism is defined as susceptible by a level of antimicrobial activity
associated with a high likelihood of therapeutic success
• a microorganism is categorized as susceptible (S) by applying the appropriate
breakpoint in a defined phenotypic test system
EUCAST has re-defined susceptible,
intermediate and resistant and defined the
Clinically Intermediate (I)
terms
wildas type
andbynon-wild
type activity
• a microorganism
is defined
intermediate
a level of antimicrobial
associated with indeterminate therapeutic effect
microorganism…..
• a microorganism is categorized as intermediate (I) by applying the appropriate
breakpoints in a defined phenotypic test system
and agreed…
Clinically Resistant (R)
• a microorganism is defined as resistant by a level of antimicrobial activity associated
with a high likelihood of therapeutic failure.
• a microorganism is categorized as resistant (R) by applying the appropriate
breakpoint in a defined phenotypic test system
Clinical breakpoints may be altered with legitimate changes in circumstances
Clinical breakpoints are presented as S<x mg/L; I>x, <y mg/L; R>y mg/L
EUCAST definitions of epidemiological
cut off values
available at www.eucast.org
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<z mg/L and non-wild type as NWT >z mg/L
EUCAST publications
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
European Committee on Antimicrobial Susceptibility Testing. (2000). Terminology relating to
methods for the determination of susceptibility of bacteria to antimicrobial agents. EUCAST
Definitive Document E.Def 1.2. Clinical Microbiology and Infection 6, 503-8.
European Committee on Antimicrobial Susceptibility Testing. (2000). Determination of
antimicrobial susceptibility test breakpoints. EUCAST Definitive Document E.Def 2.1. Clinical
Microbiology and Infection 6, 570-2.
European Committee on Antimicrobial Susceptibility Testing. (2000). Determination of
minimum inhibitory concentrations (MICs) of antibacterial agents by agar dilution. EUCAST
Definitive Document E.Def 3.1. Clinical Microbiology and Infection 6, 509-15.
European Committee on Antimicrobial Susceptibility Testing. (2001). Linezolid breakpoints.
EUCAST Definitive Document E.Def 4.1. Clinical Microbiology and Infection 7, 283-4.
European Committee on Antimicrobial Susceptibility Testing. (2003). Determination of
minimum inhibitory concentrations (MICs) of antibacterial agents by broth microdilution.
EUCAST Discussion Document E.Def 5.1. Clinical Microbiology and Infection 9 (issue 7
insert) 1-10.
Ridgway, G.L., Bébéar, C., Bébéar, C.M, et al. (2001). Antimicrobial susceptibility testing of
intracellular and cell-associated pathogens. EUCAST Discussion Document E.Dis 6.1. Clinical
Microbiology and Infection 7 (issue 12 insert),1-10.
Rodriguez-Tudela, J.L., Barchiesi, F., Bille, J. et al. (2003). Determination of minimum inhibitory
concentrations by broth microdilution of fermentative yeasts. EUCAST Discussion Document
E.Dis 7.1. Clinical Microbiology and Infection 9 (issue 8 insert), 1-8.
Drobniewski, F. (2002). Antimicrobial susceptibility testing of Mycobacterium tuberculosis.
EUCAST Discussion Document E.Dis 8.1. Clinical Microbiology and Infection 8 (issue 10
insert),1-10.
Kahlmeter G, Brown DFJ, Goldstein FW et al. (2003) European harmonization of MIC
breakpoints for antimicrobial susceptibility testing of bacteria. Journal of Antimicrobial
Chemotherapy 52, 145-148.
Kahlmeter G & Brown D. Harmonisation of European breakpoints – can it be achieved?
Clinical Microbiology Newsletter, in press.
Published documents, discussion documents and tentative
decisions are posted on the EUCAST website.
Tentative decisions and discussion documents - after a
period of consultation they will be submitted for publication
and/or be made available on the EUCAST website as final
documents or decisions (www.eucast.org).
EUCAST Subcommittee on Antifungal
Susceptibility Testing
(EUCAST AFST)
• develop reference methods for antifungal susceptibility testing
• set breakpoints for antifungal drugs
Financed through EUCAST
EUCAST processes for breakpoint setting, decisions and consultation
EUCAST collaborations
• EMEA – SOP being developed which renders EUCAST the official
European breakpoint committee (EUCAST breakpoints in the SPCs).
• Expert groups and reference laboratories (Neisseria, Salmonella,
European Veterinary working group, NEQAS)
• EARSS
– EUCAST permanently on the EARSS advisory board
• NCCLS
– NCCLS/EUCAST broth dilution method for the determination of MIC-values
harmonised through CEN and ISO; finished document end of 2004.
– NCCLS/EUCAST common QC type strain MIC-target values and ranges
– NCCLS/EUCAST harmonised FQ breakpoints for staphylococci.
– Collaborative process for revision of cephalosporin and carbapenem MIC
breakpoints (first joint meeting in Tampa, January 2005).
•
Pharmaceutical industry information and consultation network
Liaison with NCCLS
Breakpoints for new antimicrobials
• Daptomycin
• Tigecycline
EUCAST procedure for setting
breakpoints
The next 9 slides describe the EUCAST procedure
for harmonising European breakpoints.
1. Data on dosing, formulations, clinical indications and target
organisms are reviewed and differences which might influence
breakpoints are highlighted
Example: ciprofloxacin
National breakpoint committees
BSAC
UK
CA-SFM
France
CRG
Netherlands
DIN
Germany
NWGA
Norway
SRGA
Sweden
Most common dose
500 x 2 oral
400 x 2 iv
500 x 2 oral
200 x 2 iv
250 x 2 oral
200 x iv
500 x 2 oral
200 x 2 iv
200-400 x 2
oral
400 x 2 iv
500 x 2 oral
400 x 2 iv
Maximum dose schedule
750 x 2 oral
400 x 3 iv
750 x 2 oral
400 x 3 iv
750 x 2 oral
400 x 3 iv
750 x 2 oral
400 x 2 iv
data pending
750 x 2 oral
400 x 3 iv
oral, iv
oral, iv
oral, iv
oral, iv
oral, iv
oral, iv
Dosage
Available formulations
Clinical data
There is clinical evidence for ciprofloxacin to indicate a poor response in systemic infections caused by Salmonellae
with low-level fluoroquinolone resistance (MIC>0.064 mg/L) EUCAST has suggested that the epidemiological cut off
value (S<0.064/R>0.064 mg/L) be used in Salmonellae systemic infections. These strains are best found using a
nalidixic acid 30 µg screen disc in routine susceptibility testing.
There is agreement in EUCAST that ciprofloxacin activity against Enterococci and Streptococci, including
S.pneumoniae, is insufficient to categorize wild type bacteria “susceptible”.
2. Multiple MIC-distributions are collected, the wild type MIC
distribution is defined and tentative epidemiological cut-off values
determined (WT < X mg/L)
Epidemiological
cut off: WT<2.0
3. Existing national clinical breakpoints are compared
Ciprofloxacin was used in this example:
Breakpoints prior to harmonisation (mg/L) S< / R>
General breakpoints
BSAC
CA-SFM
CRG
DIN
NWGA
SRGA
ND
1/2
1/2
1/2
0.125/2
1/2
Species related breakpoints
not yet
NCCLS
no
Enterobacteriaceae
1/1
0.12/2
0.12/1
1/2
Pseudomonas spp.
1/4
ND
1/1
1/2
1/1
1/2
0.12/2
0.06/2
1/2
Acinetobacter spp.
Staphylococci
1/1
Streptococci
1/1
excluded
0.12/2
0.12/2
excl
2/2 (I)*
excluded
0.12/2 (I)*
0.12/2 (I)*
excl
excluded
excluded
0.12/2
0.12/2
1/2
0.12/0.5
0.12/0.25
1/-
S. pneumoniae
Enterococci
Haemophilus/Moraxella spp.
1/1
Corynebacteria
N. Meningitidis
N. Gonorrhoeae
excl
1/1
0.06/-
0.06/1
0.06/0.12
0.03/0.25
0.06/0.12
0.06/0.25
P. Multocida
ND
ND
0.12/0.25
Anaerobes
excluded
ND
excluded
no
no
Campylobacter spp.
1/1
Helicobacter pylori
2/2
no
no
0.06/0.5
4. Using available PK/PD data, Monte Carlo simulations
are performed and a tentative breakpoint calculated
”Minimum requirement for Scategory” is that the high MIC
value of the wild type MICdistribution is consistent with
the MIC derived from the
PK/PD index needed for
optimal efficacy based on free
drug”.
5. Clinical data relating outcome to MIC-values
and resistance mechanisms are assessed in
relation to the tentative breakpoint
….and you´ve just heard
Professor MacGowan adress
that issue
6. Tentative breakpoints are checked against target species wild
type MIC distributions to avoid splitting the wild type
…it was decided to set the
break-point at S≤0.125
and R>2 mg/L, rendering
wild type S.pneumoniae
inter-mediately
susceptible to
ciprofloxacin.
<2 mg/L
Epidemiological
cut off: WT<2.0
To permit reproducible
susceptibility testing,
splitting of the wild type
must be avoided:
0.5 and 1 mg/L were not
acceptable….and 2 mg/L
was considered too high…
7. Consultation process on tentative breakpoints
- national committees
- EUCAST general committee
- pharmaceutical industry, AST device manufacturers
- others via EUCAST website
8. Re-appraisal of tentative breakpoints following comments
9. Further consultation if required
EUCAST has now finalised breakpoints for fluoroquinolones,
glycopeptides, aminoglycosides and linezolid and is now
EUCAST
breakpointcarbapenems
tables areand
published
working
on cephalosporins,
aztreonam.
at www.eucast.org
EUCAST websites are found at
www.eucast.org
The EUCAST website is a section of the official ESCMID
website – it gives details of all EUCAST activities including
- constitution and organisation
- committee member lists
- meetings
- EUCAST documents
- EUCAST power-point presentation
- 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.
Choose to display in English, French or German
First screen of the EUCAST program for the display of wild
type MIC distributions in microorganisms.
www.eucast.org
EUCAST aggregated wild type MIC
distributions
- the fact that wild type microrganisms of the same species
exhibit identical MIC (and inhibition zone) distributions
irrespective of origin provides an opportunity to aggregate
multiple distributions and define a reference.
•
Data from scientific papers, breakpoint committees, reference laboratories,
pharmaceutical industry, surveillance networks (EARSS, Sentry, Alexander
Project, National surveillance networks)
•
All submitted full-range MIC distributions accepted
•
To date no systematic exclusions.
•
October, 2004 – 3500 MIC distributions
0
512
16
256
52
128
28
64
4
32
1
16
0
8
0,125
0
4
0,064
0
2
0,032
0
1
0,016
0
0,5
0,008
0
0,25
0,004
S.pneumoniae
0,002
S. pneumoniae and ciprofloxacin MIC distributions
0
0
0
0
0
0
0
S.pneumoniae
0 0 0 0 0 0
1191 671 101 21 2 0 2 3
This0 slide
shows a portion0 of55the
data set for
S.pneumoniae
0
0
0
0
0
0
0
4
45
363
454 119 11 0 0 0 0
S.pneumoniae and ciprofloxacin.
S.pneumoniae
0 0 0 0 0 0 0
2
2
15 32
2 0 1 0 0 0
S.pneumoniae
0 0 0 0 0 0 3 80 256
61 11
1 1 0 0 0 0
Each
MIC
distribution
is
from
a
different
investigator,
S.pneumoniae
0 0 0 0 0 0 1
5 64 155 17
4 0 0 0 0 0
surveillance
program, breakpoint
committee
or
S.pneumoniae
0 0 0 0 0 0 1
4 35 130 51
3 0 0 0 0 0
pharmaceutical company.
S.pneumoniae
0 0 0 0 0 0 1 197 251
41 10
1 0 1 0 0 0
S.pneumoniae
0 0 0 0 0 0 1 16 125 102 28
3 0 0 0 0 0
The
median
of
the
unior
of
the
first
part
of
the bi- or multiS.pneumoniae
0 0 0 0 0 0 1
8 96 209 59
1 2 0 0 1 0
modal
distribution has been marked
in blue.
S.pneumoniae
0 0 0 0 0 0 3 20 92
69 10
3 1 0 0 0 0
S.pneumoniae
0 0 0 0 0 0 2
5 161 544 64 10 0 2 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
S.pneumoniae
S.pneumoniae
S.pneumoniae
S.pneumoniae
S.pneumoniae
S.pneumoniae
S.pneumoniae
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
6
3
0
2
0
0
0
4
0
1
0
0
0
0
4
2
3
3
0
0
0
13
22
9
13
2
2
2
245 854 379
225 917 401
426 933 138
402 1193 222
75 366 182
36 409 186
207 1052 225
9 6 1
16 3 2
11 5 2
19 10 0
30 4 0
29 2 1
22 2 10
1
4
1
6
0
1
0
1
1
0
0
2
1
1
0
0
2
0
0
0
0
Aggregated S.pneumoniae ciprofloxacin MIC-data.
Values of >1% are shown in graph as bars.
Choose to display in English, French or German
www.eucast.org
Specify the drug or the bug (never both) - after a moment 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.
(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
EUCAST wild type MIC distributions – templates for calibration of
MIC determinations
Laboratories which cannot fit their own MIC data to the the EUCAST
reference distribution should look into the following possibilities:
•
The method used for MIC
determination in the local set of
data is not adequately standardised
or calibrated,
•
The species identification is
incomplete
•
There are too few determinations to
allow identification of the part of
the distribution that constitutes the
wild type microorganisms (which
usually corresponds to the four
lowest dilution steps).
Examples from the EUCAST wild type
MIC distribution program.
1
The objectives of EUCAST are
•
to form in EUCAST, under the auspices of the European Society of Clinical Microbiology and
Infectious Diseases", a professional network of
- the national breakpoint committees and experts on antimicrobial susceptibility testing and
- industry involved in the production and marketing of antimicrobial agents or of in-vitro diagnostic
medical devices used in antimicrobial susceptibility testing;
•
to set common European breakpoints for surveillance of antimicrobial resistance;
•
to identify national differences in clinical breakpoints and to harmonise breakpoints for existing and
new antimicrobial drugs;
•
to produce, disseminate and update a series of documents on the technology of in-vitro antimicrobial
susceptibility testing, promoting standardisation of methods used in different parts of Europe and
comparability of results obtained by different technologies;
•
to encourage internal and external national and international quality assessment schemes;
•
to collaborate with European and international groups concerned with antimicrobial susceptibility
testing and/or the epidemiology of antimicrobial resistance;
•
to advise European Community Institutions on the technology and interpretation of antimicrobial
susceptibility testing;
•
to work with groups outside Europe (eg NCCLS) to achieve international consensus on
susceptibility testing;
•
to devise and participate in educational and training programmes for antimicrobial susceptibility
testing (workshop with EARSS in 2005, two workshops for national breakpoint committees in 2005 &
2006).
The End
E.coli and ciprofloxacin in ECO•SENS
Wildtype distributions do not vary with geographical origin!
25
25
Canada
20
15
15
10
10
5
5
0
0
5
10 15 20 25 30 35 40 45 50 55 60 65 70
25
0
0
15
10
10
5
5
0
0
5
10 15 20 25 30 35 40 45 50 55 60 65 70
E.coli ATCC 25933 vs Ciprofloxacin 10 µg
20
15
0
5
25
Spain
20
Sweden
20
10 15 20 25 30 35 40 45 50 55 60 65 70
0
5
10
15
G Kahlmeter, JAC, 2003.
20
25
30
35
40
45
50
55
60
65
70
Wildtype distributions do not vary with geographical origin!
S.p n e u mo n iae
vs.
o xacillin 1 µg
% strains
Kronoberg county, Sw eden
Pondicherry, India
0
6
10
20
Zone diameter (mm)
C.Lars s on et al, Clin Mic robiol Infec t, 1999
30
40
E.co li v s. Co tr imo xazo le
Origin
% strains
E.coli, pig and poultr y (n=100)
20
0
E.coli, cons ecutive hum an
is olates (UTI, n=100)
-2 0
6
10
15
20
zone diameter (mm)
30
40
Origin
S.au r e u s v s. clin d amycin
Veterinary v s human isolates
% isolates
Human strains (consec clinical)
Veterinary strains
0
6
8
10
12
14
16
18
20
22
24
26
28
Zone diameter (mm)
30
32
34
36
38
40
42
44
46
Summary of EUCAST procedure for setting
clinical breakpoints
1.
Data on dosing, formulations, clinical indications and target organisms are
reviewed and differences which might influence breakpoints are highlighted.
2.
Multiple MIC-distributions are collected, the wild type MIC distribution is
defined and tentative epidemiological cut-off values determined (WT < X mg/L).
3.
Existing national clinical breakpoints are compared.
4.
Using available PK/PD data, Monte Carlo simulations are performed and a
tentative breakpoint calculated. ”Minimum requirement for S-category” is that
the high MIC value of the wild type MIC-distribution is consistent with the MIC
derived from the PK/PD index needed for optimal efficacy based on free drug”.
5.
Clinical data relating outcome to MIC-values and resistance mechanisms are
assessed in relation to the tentative breakpoint.
6.
Tentative breakpoints are checked against target species wild type MIC
distributions to avoid splitting the wild type.
7.
Consultation process (national committees, EUCAST general committee and
pharmaceutical industry and AST device manufacturers).
8.
EUCAST clinical breakpoint tables are published on the internet
(www.eucast.org) with links to tables and graphs of wild type distributions of
MIC values.
How to implement EUCAST breakpoints
• The national breakpoint committees have committed themselves to
implementing EUCAST breakpoints – which means that anyone
using the national European systems will gradually adhere to the
EUCAST breakpoint system
• 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.
EUCAST wild type MIC distributions and
epidemiological cut-off values – the concept
JAC 2003; 52: 145-148
EUCAST developed the concept of antimicrobial wild type MIC
distributions and epidemiological cut-off values (JAC 52:145-148, 2003).
Software was created to receive and display large volumes of MIC data
for bacteria and fungi over the Internet. It is freely available at
http://www.eucast.org.
Distributions are displayed in an aggregated format. Tables and graphs
show the part of the MIC distribution which, when EUCAST defines the
”epdemiological cut-off value”, is defined as the ”wild type distribution”.
The epidemiological cut-off value separating microorganisms without
(wild type) and with acquired or mutational resistance (non-wild type) and
clinical breakpoints are, if defined, shown on the bottom line of the
graph.
The epidemiological cut-off value (left hand lower corner) is shown as WT≤ X mg/L.
The clinical breakpoints (right hand lower corner) are shown as S≤ Y mg/L and R> Z mg/L.
EUCAST wild type MIC distributions and epidemiological cut-off
values – methods and data
Origin of MIC data
Each distribution is comprised of aggregated MIC data including individual MIC distributions
from
- publications in international journals
- breakpoint committees
- antimicrobial surveillance systems such as EARSS, SENTRY, the Alexander Project
- pharmaceutical companies and susceptibility testing device manufacturers.
Thus, unless otherwise specifically stated, distributions include results obtained with
different methods. These methods do not give exactly the same results but the results
rarely vary by more than one doubling dilution step. In this way the aggregated EUCAST
MIC distributions contain the random variation between different investigators and the
systematic variation seen between different methods.
Origin of the organisms included in the MIC distributions
The data are from tests on bacteria and fungi collected from man and animals, of any
geographic origin and over a wide timeframe.
MIC methods represented
Species-specific distributions of MIC values collected from all over the world are included in
the database. The distributions shown represent full range MIC values determined with
methods described by EUCAST, BSAC (UK), CA-SFM (France), CRG (The Netherlands),
DIN (Germany), NCCLS (USA), NWGA (Norway), and SRGA (Sweden) or methods
calibrated to these methods (eg. commercial methods which give full range MIC values).
EUCAST wild type MIC distributions – templates for calibration of
MIC determinations
Exclusion of data
All submitted full-range MIC distributions have been accepted. There has been no
systematic exclusion of data from one contributor or from one method. The
contributions are screened by the EUCAST Steering Committee and less than 10%
have been excluded from the aggregated distributions. However, all data are held in
the database and are accessible to the Steering Committee. The most common
reason for exclusion has been that the data were not full-range MICs so that a
significant proportion of MICs were outside the tested range.
Laboratories which cannot fit their own MIC data
to the the EUCAST reference distribution should
look into the following possibilities:
•
The method used for MIC determination in the
local set of data is not adequately calibrated,
•
The species identification is incomplete,
•
There are too few determinations to allow
identification of the part of the distribution that
constitutes the wild type microorganisms. This
usually corresponds to the four lowest dilution
steps.
EUCAST wild type MIC distributions
– why are only the MICs of wild type microorganisms displayed?
The distributions consist of MIC-values
determined over 30 years or more.
Resistance frequencies obtained through
the aggregated MIC distributions would not
be representative of current antimicrobial
resistance frequencies and would be
confusing and misleading.
When the epidemiological cut-off value has
been determined by the EUCAST Steering
Committee it blocks display of the non-wild
type microorganisms (red bars, upper
figure) and shows only the part
representing the wild type (lower fig).
EUCAST wild type MIC distributions
– how to contribute data
Everyone is invited to contribute data
All who have full-range MIC data for bacteria or fungi are invited to
contribute data as long as MICs are determined with an accepted
standardised method, which should be named. Once entered on the
database the data will not be identifiable as separate distributions but will
help build the aggregate reference distributions. The biologically resistant
(non-wild type) part of the distribution will be seen only by the EUCAST
Steering Committee.
Submitting data to the EUCAST database does not interfere with
publication of data.
Where can I get more information?
Contact EUCAST – email addresses and information can be obtained
through the EUCAST website at http://www.eucast.org