When There Are No Breakpoints Guidance 1 Dec 2021

Antimicrobial susceptibility tests on groups of organisms or agents for
which there are no EUCAST breakpoints

Updated 1 December 2021
There are some bacterial groups and antimicrobial agents for which EUCAST has not determined
breakpoints. Breakpoints for new agents will be set as the agents go through the marketing approval
application to the EMA and are released if the agent is granted approval. Breakpoints for some older agents
may be set when a convincing need is established (e.g. nitroxoline and temocillin). There are also some less
common organism groups (e.g. Streptomyces spp, Burkholderia cepacia group, many anaerobic bacterial
species) and agents for which breakpoints may or may not be determined. This may be the case for older
agents replaced by more modern agents with clear advantages (greater activity, improved pharmacokinetics
or reduced toxicity). For example, this is the case for the aminoglycoside kanamycin, the quinolone
sparfloxacin, the macrolide josamycin and several cephalosporins. It is also less likely that breakpoints will be
set for rarely isolated species such as E. rhusiopathiae, Campylobacter spp. other than C. jejuni and C. coli,
and groups for which there are difficulties in devising reproducible testing conditions such as Acinetobacter
spp. for cephalosporins and Stenotrophomonas maltophilia for many agents. In the absence of a breakpoint,
it will not be possible to proceed with assessment based on phenotypic testing unless a trustworthy and
reproducible MIC value can be obtained for the isolate.
If an MIC can be reliably determined, then guidance can be given. Disk diffusion cannot be used unless
correlation with MIC values has been established. Gradient tests cannot be used unless the manufacturer
states that it has been validated for use with the species in question. In some cases, it is relevant to search
the literature to obtain advice on which antimicrobials to include in the testing. However, note that
reporting bacteria “Susceptible” means that there is clinical evidence that the agent will work in infections
caused by the species - if such evidence is lacking, the report can at best state that the isolate exhibits an in
vitro susceptibility that is within the range of typically susceptible species.
For aerobic and facultative aerobic bacteria

When there are PK/PD breakpoints for the agent, guidance on interpretation of the MIC is available from
the EUCAST rationale document and the EUCAST breakpoint table (www.eucast.org), where PK/PD-based
breakpoints and dosages are listed. When PK/PD breakpoints are not available, reliable PK/PD data have not
been identified. On occasion there may be a discrepancy between the rationale document and the
breakpoint table – the latter is updated yearly and takes precedence over the former.
• An MIC which is less than or equal to the PK/PD susceptible breakpoint, suggests that the agent can
be used with caution. Include a note that the guidance is based on PK/PD breakpoints and include
the MIC and dosage on which PK/PD breakpoint is based.
• If the MIC is greater than the PK/PD breakpoint for resistance, advise against use of the agent.
Categorical reporting should be avoided when there are no specific breakpoints.

Reporting should instead be in the form of guidance (see below).
When there are no PK/PD breakpoints but wild type MIC distributions are available, it is useful to
determine whether the MIC for the isolate is consistent with or higher than those of the wild type MIC
distribution for the species. Access the EUCAST MIC distribution website and enter either the name of the
species or of the agent. If there is a distribution for the relevant species and agent, you will be able to decide
whether the MIC you have obtained from testing belongs to the wild type or not. If the MIC is inside the wild
type, comparison can be made with other species for which a clinical categorisation of the wild type already
exists (i.e. breakpoints have already been determined). Categorical reporting should be avoided when there
are no specific breakpoints. Reporting should instead be in the form of guidance (see below).
When there are neither PK/PD breakpoints nor wild type MIC distributions.
Assume you aim to find out whether or not an isolate of Arcanobacterium haemolyticum is susceptible to
erythromycin. The MIC is determined as 0.5 mg/L. There is no PK/PD breakpoint for erythromycin and there
is no MIC distribution for the species. However, from the breakpoint table you will discover that the MIC
value of the isolate would for other gram-positive bacteria have been categorised as “Susceptible”. In your
report, note that guidance is based on the comparison of the isolate with organisms of the same or similar
species. Categorical reporting of S, I and R should be avoided, and reporting should instead be in the form of
guidance (see below).
For anaerobic bacteria

For anaerobic species where breakpoints have not been established* and where MIC distributions may be
lacking or are incomplete, EUCAST proposes that an MIC value can be cautiously interpreted using the values
in the table below. These are based on breakpoints for other species and breakpoints previously used for
anaerobic bacteria. They are often overlapping with PK/PD breakpoints.
Determine the MIC using agar dilution or following the instructions of the manufacturer of the MIC
product/device. If the MIC is above the values presented in the table, advise against the use of the agent for
treatment (alternatively “report as resistant”). If the MIC is equal to or below the value, interpret with
caution and avoid categorical reporting. Reporting should instead be in the form of comments to guide (see
below).
Antimicrobial agent relevant for the Resistance (R>) for species lacking
treatment of anaerobic bacteria specific breakpoints*
Benzylpenicillin 0.5
Piperacillin-tazobactam 8
Meropenem 2
Vancomycin 2
Clindamycin 0.5
Metronidazole 4
*These breakpoints should not be used for species with specific breakpoints: Bacteroides spp, Prevotella spp,
Fusobacterium necrophorum, Clostridium perfringens, Cutibacterium acnes, Clostridioides difficile – see the
EUCAST breakpoint table.
The following anaerobic gramnegative and grampositive bacteria do not currently have species specific
breakpoints and are eligible for interpretation with the values in the table. Among gramnegative anaerobic
bacteria are Bilophila, Mobiluncus, Parabacteroides and Porphyromonas. Among grampositive anaerobic
bacteria are Actinomyces, Bifidobacterium, other clostridia, Eggerthella, Eubacterium and Lactobacillus. The
group also includes a number of anaerobic Gram-positive cocci, including Staphylococcus saccharolyticus.
Anaerobes are most frequently defined by no growth when incubated in a CO2 enriched atmosphere, but
several species may grow to some extent in atmospheres that are not strictly anaerobic. For all these
species, susceptibility testing should be performed in anaerobic environment.
Reporting susceptibility when there are no breakpoints

Once one of the techniques proposed above have been used to evaluate whether an isolate is or is not likely
to respond to therapy with a specific agent, the result should be reported.
If you failed to develop a reasonable recommendation, add a comment:

• Categorising the susceptibility of the organism is not possible. There is no approved method and
breakpoints have not been determined.
• Categorising the susceptibility of the organism is not possible. The MIC is X mg/L.
If the aim is to discourage the use of an agent, you may or may not want to add an R to the report with a
comment:
• Formal categorising of the susceptibility of the organism is not possible. The MIC (of X mg/L)
suggests that the agent should not be used for therapy.
If the aim is to encourage the use of an agent, you can add a comment:
suggests that the agent may be used for treatment.
Is the species an anaerobic bacterium?
No Yes
Are there PK/PD breakpoints? See the ANAEROBE table of R> values and
interpret cautiously
No Yes
Interpret according to the

Is there an MIC distribution?
PK/PD breakpoint
No Yes
Compare the MIC with those of

Compare with other species with
related bacteria and when these
similar wild type distribution and when
have clinical breakpoints,
these have a clinical breakpoint
interpret with caution.
If no recommendation can be achieved, report:

• Categorising the susceptibility of the organism is not possible. There is no approved method
and breakpoints have not been determined.
• Categorising the susceptibility of the organism is not possible. The MIC is X mg/L.
If the aim is to discourage the use of an agent, you may or may not want to add an R to the
report with a comment:
suggests that the agent should not be used for therapy.
If the aim is to encourage the use of an agent, you can add a comment:
suggests that the agent may be used for treatment.

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Antimicrobial susceptibility tests on groups of organisms or agents for

which there are no EUCAST breakpoints

For aerobic and facultative aerobic bacteria

Categorical reporting should be avoided when there are no specific breakpoints.

For anaerobic bacteria

Reporting susceptibility when there are no breakpoints

If you failed to develop a reasonable recommendation, add a comment:

Interpret according to the

Compare the MIC with those of

If no recommendation can be achieved, report:

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