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Annex 9: Final report Defra project OD2006
Annex 9.1: A summary of international antimicrobial use guidelines
Compiled by Andrew Wales
General
Much of the guideline advice (all of the BVA, OIE and German documents, and the fifteenpoint framework from AVMA) is not species-specific. Much of this general advice is
included below, under species headings because it relates to other, species-specific,
guidelines from other sources. The guidelines outline many general principles and use
concepts subject to veterinary interpretation (such as ‘clinically appropriate/relevant’ and
‘justified use’). The general thrust of the advice is to use narrow-spectrum antimicrobials
whenever possible, as infrequently and for as short a time as possible, under the control of
a veterinarian who has detailed and up-to-date knowledge of the animal production unit.
The importance of hygiene and management procedures, as well as the roles of
vaccination and biosecurity are emphasized in all guidelines.
Specific and detailed advice about the selection and use of antimicrobials in particular
situations is given in the Dutch documents for pigs and poultry, in the AVMA and
Norwegian/Swedish documents for poultry, although fluoroquinolone use is specifically
addressed in several other sources. There is no specific advice on detecting and
assessing prevailing resistance patterns on-farm, on the acquisition and selection for
multiple resistances, nor on the use of antimicrobials in animals with an immature gut flora.
Whilst most documents appear to give veterinarians and farmers fairly wide scope in the
use of therapeutic and preventative antimicrobials, there is also in most cases an initial
emphasis on the importance of sound husbandry and preventive medicine in minimising
the requirements for antimicrobial use. In the RUMA documents, this is expanded into
detailed advice on management, husbandry, vaccination, health testing and dealing with
sick animals.
The OIE document additionally sets out standards for the operation of regulatory
authorities, the veterinary pharmaceutical industry, and veterinary wholesale and retail
distributors. In the process of licensing, regulatory authorities are advised not to attempt to
generalise data from one antimicrobial to another within the same class. Furthermore,
assessment for licensing should include detailed consideration of the potential to select for
resistance, in the context of existing resistance patterns amongst pathogens and
commensals of humans and animals. Pharmacological studies and modelling should be
used to select dosages and regimes that are efficacious and minimise the generation of
resistance. An environmental impact assessment should be performed. Once an
antimicrobial drug is licensed, regulatory authorities have a responsibility to conduct or
direct surveillance, using existing pharmacovigilance reporting and also via specific, active
surveillance of the target pathogen, other food-borne pathogens and commensals. The
veterinary pharmaceutical industry is exhorted to discourage the advertising of
antimicrobials directly to food producers.
Poultry (based upon the BVA, BVPA and RUMA documents)
There should be an integrated disease control policy for each unit/farm, including a
documented preventive medicine programme with policies on specific endemic diseases,
agreed between the veterinarian and farmer. The emphasis should be on good
management, husbandry, vaccination, competitive exclusion where appropriate, identifying
problems at source and reductions in antimicrobial use. There should be a precautionary
principle exercised, prioritising the preservation of efficacy of antimicrobials that are
important for human use. All prescribing is under veterinary care and real, not nominal,
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Annex 9: Final report Defra project OD2006
veterinary care requires a sound knowledge of the management system and health status
of the flock; if this is not in place, the unit must be visited before prescribing. Where
biosecurity limits veterinary visits, formal rules of communication must be established
between vet and farmer. Veterinary prescriptions should precisely state the dose, dosing
intervals, duration, withdrawal periods and total drug used (OIE) and the vet should be
available for follow-up after prescribing (AVMA). There should be regular veterinary
assessment of long-term antimicrobial use in control programmes. There is a veterinary
responsibility for Continuing Professional Development.
Antimicrobials may be used where an infectious agent is known or suspected to be
present (‘when clinically appropriate’, i.e. not in uncomplicated viral conditions - AVMA)
and an accurate diagnosis should be made (with reference to the importance of on-farm
post-mortem and other diagnostic examinations - Norway/Sweden). Some agents
(specifically Salmonella) do not routinely require antimicrobial medication. Use of
antimicrobials in the absence of a specific infection requires clear justification. Do not use
before an exact diagnosis has been established unless symptoms are severe (Germany).
The sensitivity of the infectious agent to the antimicrobial should be established, especially
after the failure of initial treatment or in intensive units (or after recurrence or before
second-line antimicrobial use [OIE] or before changing drugs, regular or repeated use, use
in combination with another antimicrobial or off-label use [Germany], or always
[Norway/Sweden]). The number of animals treated should be minimised, limiting treatment
to ill or at-risk animals (AVMA). Farmers should isolate sick animals and dispose of dead
and dying animals properly (OIE). Preventative treatment should be justified with respect
to the presence or risk of disease and the immune status of the animals, with use in the
absence of disease requiring a clear justification and a written policy on prophylactic use
by each veterinary practice.
When selecting an antimicrobial, consideration should be given to the spectrum of activity
(narrowest possible), pharmacokinetics, immune status of animals and the prognosis of
the condition. The use of fluoroquinolones should be at an absolute minimum
(Norway/Sweden) or only where sensitivity or clinical experience indicates effectiveness.
Using listed criteria, the Dutch ‘formularium’ describes first-, second- and third-choice
antimicrobials for 21 infections, which are expected to be adhered to, with careful
justification required before deviating from the cascade. Three classes of antimicrobials
are determined by AVMA, with a cascade of options, and specific guidelines for the
treatment of colisepticaemia, Pasteurellosis, Necrotic Enteritis, Staphylococcus,
Erysipelas, mycoplasmas and salmonellae. The Norwegian/Swedish document divides
antimicrobials available into (at least) four classes for any indication; classes I, II and III
being ‘labelled use in-country’, ‘labelled use in another EU country’, and ‘licensed for
another species’, respectively, with specific guidelines given for E. coli, necrotic enteritis
and coccidiosis. No off/extra-label use of drugs not licensed for food-producing animals is
permitted in the UK. The off-label use of drugs needs careful justification and such use of
fluoroquinolones is strongly discouraged. The Dutch ‘formularium’ recommends certain offlabel uses. The Animal Medicinal Drug Use Clarification Act (AMDUCA) in USA states that
if a labelled, effective drug exists for a situation, it must be used. Furthermore, extra-label
use of certain drugs, including enrofloxacin, is prohibited (AVMA). All off-label use should
be supported by culture and sensitivity testing (Germany), and requires special permission
in Norway/Sweden.
The use of antimicrobials requires attention to adequate (i.e. not sub-therapeutic) dosages,
using the best available information to limit target and collateral resistance. Check the
stock-keeper understands the schedule, has written instructions (Germany), and avoid
oversupply. Courses should be as short as possible for adequate clinical response (AVMA,
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Germany) and there should be regular veterinary review in cases of long-term or repeated
use. There should be careful attention to all withdrawal periods, particularly following offlabel use of an antimicrobial.
Vets should keep records of all antimicrobials administered to food-producing animals, and
farmers should keep detailed records of antimicrobial use. There should be periodic
veterinary review of farm records (OIE). Outcomes should be recorded (Germany) and
routine monitoring should include screening for Salmonella, especially multi-resistant
subtypes. Trends in antimicrobial sensitivity should be monitored and recorded. Any
suspected microbial resistance should be reported to authorities (Germany); similarly with
suspected adverse reactions. Environmental contamination with antimicrobials should be
minimised where possible (AVMA).
Pigs (based upon the BVA, PVS and RUMA documents)
There should be an integrated disease control policy for each unit/farm, including a written
preventive medicine programme with policies on specific endemic diseases, agreed
between the veterinarian and farmer. The emphasis should be on good management,
husbandry, vaccination, identifying problems at source and reductions in antimicrobial use.
There is a model health planner available from the PVS, and there is specific advice on
enteric and respiratory diseases, plus detailed guidelines for farmers on preventive
medicine and best practice for the handling of antimicrobials on-farm, in the RUMA
document. There should be written procedures for the periodic review of regular or longterm use of antimicrobials, with an emphasis on potential alternatives. Veterinary
prescriptions should precisely state dose, dosing intervals, duration, withdrawal periods
and total drug used (OIE) and the vet should be available for follow-up after prescribing
(AVMA). There is a veterinary responsibility for Continuing Professional Development.
Antimicrobials may be used where an infectious agent is known or suspected to be
present (‘when clinically appropriate’, i.e. not in uncomplicated viral conditions - AVMA)
and an accurate diagnosis should be made, with reference to the importance of postmortem and other diagnostic examinations. Do not use before an exact diagnosis has
been established unless symptoms are severe (Germany). The sensitivity of the infectious
agent to the antimicrobial should be established, especially after the failure of initial
treatment or in intensive units (or after recurrence or before second-line antimicrobial use
[OIE] or before changing drugs, regular or repeated use, use in combination with another
antimicrobial or off-label use [Germany]). Minimise the number of animals treated,
(AVMA). Farmers should isolate sick animals and dispose of dead and dying animals
properly (OIE). Preventative treatment should be justified with respect to the presence or
risk of disease and the immune status of the animals. There should be no preventative use
of fluoroquinolones.
When selecting an antimicrobial, consider the spectrum of activity (narrowest possible),
pharmacokinetics, immune status of animals and prognosis of the condition. Use
fluoroquinolones only where sensitivity or clinical experience indicates effectiveness.
Drugs of importance in treating refractory infections in humans and animals should be
used only after review (AVMA), or under short-term, strict conditions (Germany).
Epidemiological and resistance patterns on the unit should be taken into account (OIE,
Germany). Using listed criteria, the Dutch ‘formularium’ describes first-, second- and thirdchoice antimicrobials for 20 infections, which are expected to be adhered to, with careful
justification required before deviating from the cascade. No off/extra-label use of drugs not
licensed for food-producing animals is permitted in the UK. The Animal Medicinal Drug
Use Clarification Act (AMDUCA) in USA states that if a labelled, effective drug exists for a
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situation, it must be used. Furthermore, extra-label use of certain drugs, including
enrofloxacin, and of any drugs in-feed, is prohibited (AVMA). All off-label use should be
supported by culture and sensitivity testing (Germany)
The use of antimicrobials requires attention to adequate (i.e. not sub-therapeutic) dosages,
written instructions to operators, the avoidance of oversupply and regular veterinary review
in cases of long-term or repeated use. Farmers should ensure feeders or header tanks are
cleaned at the end of each course of in-feed or -water medication. Courses should be as
short as possible for adequate clinical response (AVMA, Germany).
Records for each farm, including permitted antimicrobials, sensitivity results and
withdrawal times, should be held together within the veterinary practice. Vets should keep
records of all antimicrobials administered to food-producing animals, and farmers should
keep detailed records of antimicrobial use. There should be periodic veterinary review of
farm records (OIE). Monitoring of outcomes should include clinical examinations,
diagnostic tests and quarterly post-slaughter checks. Any suspected microbial resistance
should be reported to authorities (Germany) and investigated; similarly with suspected
adverse reactions. Farmers should have written, specific instructions on antimicrobial
residue withdrawal times. Environmental contamination with antimicrobials should be
minimised where possible (AVMA).
Sources of Information
OIE (Office internationale des épizooties/World Organisation for Animal Health): OIE
Terrestrial Animal Health Code - 2005
Appendix 3.9.3: Guidelines for the responsible and prudent use of antimicrobial agents in
veterinary medicine. http://www.oie.int/eng/normes/mcode/en_chapitre_3.9.3.htm
Accessed 19/09/05.
Netherlands: Documents from Dik Mevius, Central Institute for Animal Disease ControlCIDC-Lelystad, Dept. of Bacteriology and TSEs, P.O. Box 2004,
8203 AB, Lelystad, The Netherlands. Partially translated.
Norway & Sweden: proceedings of workshop on medical treatment of poultry, Nov 2003
http://www.legemiddelverket.no/terapi/publisert/Fjorfe/fjorfevev.pdf (translated summary)
BVA: http://www.bva.co.uk/members/documents/antimic.pdf
BPVA: http://www.bvpa.org.uk/medicine/amicguid.htm
PVS: http://www.bva.co.uk/members/documents/fin_pig.pdf
Unpublished drafts for latest editions of RUMA guidelines for pigs and poultry. Existing
guidelines at:
http://www.bva.co.uk/members/documents/fin_pou.pdf
http://www.bva.co.uk/members/documents/fin_pig.pdf
USA: American Veterinary Medical Association (AVMA)
http://www.avma.org/scienact/jtua/jtua98.asp
http://www.avma.org/scienact/jtua/poultry/poultry00.asp
http://www.avma.org/scienact/jtua/swine/jtuaswine.asp
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Annex 9.2: Tabulated comparisons of guidelines on prudent use of antimicrobials
Poultry
OIE (not speciesspecific) vet &
farmer
Role of
antimicrobials
Germany (not
species-specific)
Netherlands
Promotion of sound
husbandry methods,
hygienic procedures and
vaccination strategies to
minimise antibiotic use.
Norway / Sweden
UK BVA/BVPA
UK RUMA
guidelines for
farmers
USA AVMA
general / poultry
Environment, hygiene,
husbandry and vaccination
of primary importance.
Used within, not as an
alternative to, integrated
disease control policy
including management,
husbandry & vaccination.
Identify source of problem.
Document preventive
medicine programmes for
all companies/farms.
Precautionary principle
prioritising human
efficacy. Techniques such
as disinfection,
eradication, competitive
exclusion, isolation,
vaccination will minimise
use.
Preventative strategies
emphasised. Use after
other therapeutic options
considered.
All antimicrobials (except
anticoccidials & antibiotic
growth promoters) require
veterinary prescription.
Vet / client partnership, to
agree & review policy +/or
protocols, especially for
endemic conditions. All
prescribing under care of
vet.
Real, not nominal, care of
animal/flock. If not sound
knowledge of management
system & health audit,
must visit before
prescribing. Where biosecurity prevents
inspection, formal rules of
communication with client
needed.
Federal law requires use
under valid ‘Veterinary
client-patient relationship’
(VCPR): a) judgement on
need for use is vet’s
responsibility; b) vet has
knowledge for at least
general or prelim
diagnosis, i.e. either
specific or ‘medically
appropriate and timely’
visits & examinations; c)
vet available for follow-up.
Health plan with vet,
outlining preventative
measures.
Veterinary
control &
responsibilities
Proper clinical
examination before use.
Prescription should
precisely state dose,
dosing intervals,
duration, withdrawal
periods and total drug
used. Correct labelling.
Continuing Professional
Development.
Professional bodies
should develop speciesspecific guidelines.
Farmer
responsibilities
Use, only as per
prescription, on advice
of vet familiar with
animals and unit.
Attention to storage,
expiry dates, disposal of
surplus, withdrawal
times. Advise vet of
recurrent disease. Isolate
sick animals, dispose of
dead and dying animals
properly.
Veterinary control of
prescription, choice and
sale.
Strict guidelines -vets must
justify any deviation.
Initiate treatment only with
formal vet approval.
Provide accurate info to
vet. Comply with QA
schemes. Attention to poss.
interactions with other
medication. (Appendices
with much specific
guidance)
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OIE (not speciesspecific) vet &
farmer
Indications
Prescribe only when
necessary.
Criteria for Use
Diagnostics Particularly
recommended before use
of 2nd-line
antimicrobials, following
treatment failure or
recurrence.
Sensitivity
tests
Germany (not
species-specific)
Keep records of cultures
and sensitivity tests.
Only if infectious agent
present or strongly
suspected. Use before
exact diagnosis only if
symptoms severe.
Proof of agent and its
sensitivity required before:
changing drug, regular or
repeated use, combination
with other antimicrobial or
off-label use.
Netherlands
Norway / Sweden
UK BVA/BVPA
UK RUMA
guidelines for
farmers
USA AVMA
general / poultry
1 +/- 2 +/- 3-choice drugs
listed for 21 indications,
with details of deviations
from label where
considered advisable.
Specific drugs listed for:
coccidia, necrotic enteritis,
E. coli.
Use where infectious agent
known or suspected to be
present.
Colisepticaemia: many
soluble antimicrobials
appropriate. Salmonellae:
usually no treatment.
Mycoplasmas: treat
biosecurity breakdowns.
When clinically
appropriate, e.g. not
uncomplicated viral
conditions.
Necessary to correctly
diagnose.
Investigate problems
including on-farm PM
exam. Encourage further
tests, such as microbiology
& serology.
Ideally use based on
accurate diagnostics. Use
in absence of specific
infection needs clear
justification.
Culture whenever
clinically relevant.
Sensitivity should always
be established.
Sensitivity test at vet’s
discretion but especially
where treatment has failed
or in intensive units.
Should be ascertained
before, or in parallel with,
use.
Whenever clinically
relevant.
Minimise number treated.
Treat houses/flocks not all
stock.
Treatment
Prevention
Specific guidelines &
drugs for: colisepticaemia,
Pasteurellosis (Fowl
Cholera), Necrotic
Enteritis, Staphylococcus,
Erysipelas, mycoplasmas,
salmonellae.
Justified when animals
may have been exposed
to pathogen.
Needs to be justified in
respect of presence / risk
of disease & immune
status of animals. Not
fluoroquinolones. Use in
absence of disease needs
clear justification. Written
policy on prophylactic use
by each practice.
Minimise & target use of
medication for very young
birds.
Limit use to ill or at-risk
animals. Minimise number
treated.
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Drug
selection
OIE (not speciesspecific) vet &
farmer
Germany (not
species-specific)
Netherlands
Norway / Sweden
UK BVA/BVPA
UK RUMA
guidelines for
farmers
USA AVMA
general / poultry
Clinician’s experience of
efficacy, activity against
the pathogen, appropriate
route of administration,
pharmacokinetics,
epidemiological and
resistance patterns on the
unit.
Clinical experience
initially; spectrum
(narrowest preferred);
known resistance patterns;
therapeutic margin;
pharmacokinetics;
Bacteriocidal versus
-static;
immunocompetence of
animals; optimal
antimicrobial
combinations. Human
reserve drugs only for
strict indication for shortterm.
Considerations of efficacy
(bioavailability,
pharmacokinetics,
sensitivity, disorder,
clinical experience),
spectrum (narrowest
possible) and likelihood of
resistance developing.
Drugs useful against multiresistant human infection
must be rarely used.
Class I: labelled use.
Consider: spectrum
(narrowest possible),
pharmacokinetics, immune
status of animal(s),
prognosis.
Fluoroquinolones only
where sensitivity tests or
clinical experience
indicates suitability.
Fluoroquinolones
generally restricted by cost
to young/valuable stock.
Narrow-spectrum
whenever appropriate.
Bacteriostatic may be
inappropriate in chronic
infection or with immunosuppressed birds. 3 classes:
(III) no/min human use. 1st
line if possible; (II) human
use but alternatives; (I)
important human use.
Cascade is: labelled then
off-label use of III → same
for II → labelled use of I,
only after careful review &
other intervention options
have failed.
Justify all such use,
requires culture &
sensitivity
Deviation from 1, 2, 3
cascade must be carefully
justified, although
information for certain offlabel uses is provided.
Mode of Use
Combination treatment
may be necessary but the
decision and selection
should be scientifically
supported.
Off/extralabel use
Dose
In accordance with
national legislation.
Sufficiently high, especial
care with dose and
duration for oral herd
treatment. Written
instructions to owner.
Use requires consideration
and specific indication.
Absolute minimum use of
quinolones.
Three groups
1: effective, narrowspectrum, low risk of
resistance development &
spread; 2: effective,
broader spectrum, higher
resistance risk; 3: rare use,
when agent resistant to 1 &
2 isolated.
In line with data sheets,
except for certain
indications & off-label use.
Class III (?): drug
approved for a different
species, requires
‘permission’.
Class IIII: ?
Cannot use drugs not
licensed for foodproducing animals. Careful
justification. Strongly
discourage
fluoroquinolone use.
Check stock-keeper
understands dose. Don’t
use sub-therapeutic doses.
Use best available
information to minimise
target or collateral
resistance.
Some details in diseasespecific listings
Route
In compliance with law
(Animal Medicinal Drug
Use Clarification Act). No
off-label use of class I
(enrofloxacin)
Attention to dose
Water better then food for
mass medication as
consumption less affected
by disease.
Check stock-keeper
understands schedule. Use
best available information.
Schedule
Duration
Class II: labelled use in
another EU country.
As short as possible but
sufficiently long.
Avoid oversupply. Use
best available information.
Attention to course
Only as long as needed for
clinical response.
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Monitoring
Recording
OIE (not speciesspecific) vet &
farmer
Germany (not
species-specific)
In accordance with
national legislation.
Quantity, drug,
withdrawal times,
sensitivities, adverse
reactions, including lack
of response. Periodic
veterinary review to
ensure efficacy &
compliance.
Record: diagnostics,
reasons for departure from
guidelines, outcome, agent
and resistances in treated
stock.
Effects of
treatment
Record outcomes
Resistance
Report decreasing
sensitivity to authorities.
Netherlands
Norway / Sweden
UK RUMA
guidelines for
farmers
USA AVMA
general / poultry
Vets to record all
antimicrobials
administered to food
producing animals.
Farmer to record particular
and overall use, e.g. mgs
per kg birds treated per kg
birds on premises.
Record treatment and
outcomes.
Report any suspected
failure of treatment.
Sensitivity trends should
be monitored & recorded.
Monitor Salmonellae,
especially multi-resistant
types e.g. DT104.
Regular assessment of
long-term antibiotic use in
control programmes.
Regular/longterm use
Residues
Comply with withdrawal
periods.
Adverse effects
Record, and report to
authorities.
Others
UK BVA/BVPA
Off-label use requires
minimum withdrawal of 28
days for meat, 7 days eggs
in Norway. Government
discretion in Sweden.
Attention to withdrawal
times, especially when offlabel use.
Report any suspected.
Minimise environmental
contamination where
possible.
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Pigs
OIE (not speciesspecific) vet & farmer
Role of
antimicrobials
Germany (not speciesspecific)
Netherlands
Promotion of sound husbandry
methods, hygienic procedures
and vaccination strategies to
minimise antibiotic use.
Health plan with vet, outlining
preventative measures.
Veterinary
control &
responsibilities
Prescription should precisely
state dose, dosing intervals,
duration, withdrawal periods
and total drug used. Correct
labelling. Continuing
Professional Development.
Professional bodies should
develop species-specific
guidelines.
Veterinary control of
prescription, choice and sale.
Strict guidelines - vets must
justify any deviation.
UK BVA / Pig Vet
Society (PVS)
UK RUMA guidelines
for farmers
USA AVMA pigs
Used within integrated disease
control policy including
management, husbandry &
vaccination. Identify source of
problem. Written preventative
medicine programme,
emphasising antimicrobial
reduction.
Importance of management,
vaccination (erysipelas &
parvovirus as routine),
biosecurity and hygiene.
Specific guidelines on
prevention & management of
enteritis & respiratory
infections.
Preventative strategies
emphasised, i.e. husbandry,
hygiene, health monitoring,
vaccination. Use after other
therapeutic options considered.
Vet / client partnership, to agree
& review policy +/or protocols,
especially for endemic
conditions. Vet commitment to
Continuing Professional
Development. Ensure written
on-farm instructions covering:
storage, administration,
recording and withdrawals. Use
of PVS Health Planner.
Awareness of other treatments
being used. Reference to PVS
guidelines.
Federal law requires use under
valid ‘Veterinary client-patient
relationship’ (VCPR): a)
judgement on need for use is
vet’s responsibility; b) vet has
knowledge for at least general
or prelim diagnosis, i.e. either
specific or ‘medically
appropriate and timely’ visits &
examinations; c) vet or
colleague available for followup.
Vets should work closely with
farmer even for over-thecounter (OTC) antibiotics
(licensed pre-1988).
Farmer
responsibilities
Use, only as per prescription, on
advice of vet familiar with
animals and unit. Attention to
storage, expiry dates, disposal
of surplus, withdrawal times.
Advise vet of recurrent disease.
Isolate sick animals, dispose of
dead and dying animals
properly.
Draw up & review heard health
plan with vet. Accurate info to
vet. Comply with QA schemes
within constraints of animal
health & welfare. Clear
instructions to all involved.
Training in early identification
of problems. Literature on drugs
used should be available onfarm. Specific recommendations
on many aspects including:
quarantine, mixing stock,
lameness, parasite control, air
quality, manure management,
all-in/all-out, cleaning &
disinfection, pest control, injury
prevention, isolation of sick
animals, disposal of carcasses
(illegal to bury).
Work within VCPR
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Criteria for use
OIE (not speciesspecific) vet & farmer
Germany (not speciesspecific)
Indications
Prescription only when
necessary.
Diagnostics
Proper clinical examination
before use. Diagnostic tests
particularly recommended
before use of 2nd-line
antimicrobials, following
treatment failure or recurrence.
Only if infectious agent present
or strongly suspected. Use
before exact diagnosis only if
symptoms severe.
Sensitivity
tests
Keep records of cultures and
sensitivity tests.
Proof of agent and its sensitivity
required before: changing drug,
regular or repeated use,
combination with other
antimicrobial or off-label use.
Netherlands
UK BVA / Pig Vet
Society (PVS)
1 +/- 2 +/- 3 +/- ‘remaining’choice drugs (plus some
subdivisions) listed for 20
indications, with details of
relevant pharmacokinetics,
potentially problematic drug
combinations and resistance
patterns. As narrow spectrum an
absolute requirement for 1stchoice, some indications have
no 1st-choice.
Use where infectious agent
known or suspected to be
present. Population-wide
treatment must be strategic,
fewest animals possible,
shortest duration possible, and
justified either to protect
susceptible animals or minimise
excretion of infectious agent.
Necessary to diagnose correctly.
Ideally use based on accurate
diagnostics. Accurate, specified
diagnosis should be made.
Importance of post-mortem and
other diagnostic examinations.
Needs to be justified in respect
of presence / risk of disease &
immune status of animals. Not
fluoroquinolones.
Culture whenever clinically
relevant.
Whenever clinically relevant.
Early treatment of sick animals.
Justified when animals may
have been exposed to pathogen.
USA AVMA pigs
When clinically appropriate,
e.g. not uncomplicated viral
conditions. Consider
predisposing factors.
Sensitivity test at vet’s
discretion but especially where
treatment has failed or in
intensive units. Should have
prior or current sensitivity data,
plus records of previous
responses.
Treatment
Prevention
UK RUMA guidelines
for farmers
Minimise number treated.
Limit use to ill or at-risk
animals. Minimise number
treated.
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Annex 9: Final report Defra project OD2006
Drug
selection
OIE (not speciesspecific) vet & farmer
Germany (not speciesspecific)
Netherlands
UK BVA / Pig Vet
Society (PVS)
Clinician’s experience of
efficacy, activity against the
pathogen, appropriate route of
administration,
pharmacokinetics,
epidemiological and resistance
patterns on the unit.
Clinical experience initially;
spectrum (narrowest preferred);
known resistance patterns;
therapeutic margin;
pharmacokinetics; bacteriocidal
vs -static; immunocompetence
of animals; optimal
antimicrobial combinations.
Human reserve drugs only for
strict indication for short-term.
Considerations of efficacy
(bioavailability,
pharmacokinetics, sensitivity,
disorder, clinical experience),
spectrum (narrowest possible),
likelihood of resistance
developing, toxicity, residues,
environmental effects used to
classify. Drugs useful against
multi-resistant human infection
must be rarely used.
Consider: spectrum (narrowest
possible), pharmacokinetics,
immune status of animal(s),
prognosis. Fluoroquinolones
only where sensitivity tests or
clinical experience indicates
effectiveness.
Narrow-spectrum whenever
appropriate. Use of those
important in refractory human
or animal infections only after
review.
Cannot use drugs not licensed
for food-producing animals. No
use of fluoroquinolones for
growth promotion.
In compliance with law (Animal
Medicinal Drug Use
Clarification Act). Specifically,
must use labelled, effective drug
in appropriate form if it exists;
only vet or human-licensed
drugs and only under vet
supervision; in face of disease
or threat only, not for growth
promotion; appropriate
withdrawal times. No extralabel use of certain drugs (e.g.
enrofloxacin, chloramphenicol,
vancomycin). Off-label use
in/on animal feed is illegal.
Mode of use
Combination treatment may be
necessary but the decision and
selection should be
scientifically supported.
UK RUMA guidelines
for farmers
USA AVMA pigs
Three groups
1: effective, narrow-spectrum,
low risk of resistance
development & spread; 2:
effective, broader spectrum,
higher resistance risk; 3: rare
use, when agent resistant to 1 &
2 isolated. ’Remaining’ drugs:
specific licences but low
(<50%) in vitro sensitivity.
Off-label
use
In accordance with national
legislation.
Justify all such use, requires
culture & sensitivity
Deviation from 1, 2, 3 cascade
must be carefully justified.
OTC antimicrobials require
VCPR.
Dose
Sufficiently high, especial care
with dose and duration for oral
herd treatment. Written
instructions to owner.
In line with data sheets, except
for certain indications & offlabel use.
Check stock-keeper understands
dose. Written instructions.
Don’t use sub-therapeutic
doses.
Attention to correct dose
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Annex 9: Final report Defra project OD2006
OIE (not speciesspecific) vet & farmer
Germany (not speciesspecific)
Mode of use
Route
Duration
Monitoring
Some details in disease-specific
listings
Written instructions.
UK RUMA guidelines
for farmers
USA AVMA pigs
In accordance with national
legislation. Quantity, drug,
withdrawal times, sensitivities,
adverse reactions, including
lack of response. Periodic
veterinary review to ensure
efficacy & compliance.
As short as possible but
sufficiently long.
Avoid oversupply. Regular
reviews with a view to
minimising duration of use.
Give full course. Clean feeders /
header tanks at end of course.
Only as long as needed for
clinical response.
Record: diagnostics, reasons for
departure from guidelines,
outcome, agent and resistances
in treated stock.
Vets to record all antimicrobials
administered to food producing
animals. Centralise information
on each farm within vet
practice, including drugs
allowed, withdrawals &
sensitivity tests.
Record identity of pigs treated,
condition treated, drugs,
amount, expiry dates, duration,
and withdrawal period. Legal
requirement to keep 5 years.
Record vaccination & parasite
treatments.
Record treatment and outcomes.
Monitor effectiveness. Clinical
observation, serology, nasal
swabs. Quarterly post-slaughter
checks.
Record outcomes
Effects of
treatment
Record outcomes
Resistance
Report decreasing sensitivity to
authorities.
Regular/long
-term use
Residues
UK BVA / Pig Vet
Society (PVS)
Check stock-keeper understands
schedule. Written instructions.
Schedule
Recording
Netherlands
Comply with withdrawal
periods.
Adverse effects Record, and report to
Investigation of any suspected
resistance.
Regular assessment of longterm antibiotic use in control
programmes. Written
procedures for regular periodic
review of medication.
Review use regularly, especially
in respect of alternatives.
Written instructions on
withdrawals.
Attention to withdrawal times.
Reference to NOAH
Withdrawal Periods for Animal
Medicines.
Investigation of any suspected.
Farmer to report any suspected.
For extra-label use, refer to
Food Animal Residue
Avoidance Databank, i.e. no
standard withdrawal times.
authorities.
Others
Minimise environmental
contamination where possible.
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Annex 9: Final report Defra project OD2006
OIE: Responsibilities of regulatory authorities in respect of antimicrobials.
1. Marketing authorisation. Specify the terms of marketing authorisation and provide
appropriate information for veterinarians
2. Submission of data for the granting of marketing authorisation. Assess data for
marketing authorisation within criteria of safety, quality, efficacy, and risks/benefits of use.
Not to generalise data within classes of antibiotics
3. Market approval. Expedite marketing approval when a specific need for treatment exists
4. Registration procedures. Where a country’s resources do not permit an efficient
registration procedure and supplies are principally imported:
a) ensure efficient administration of imports
b) check validity of registration in manufacturing and exporting country(ies)
c) develop technical cooperation with experienced authorities to check quality and
validity of recommended use
5. Quality control, including demonstration of purity, quality, and stability under specified
storage and when mixed with water or feed
6. Assessment of therapeutic efficacy including:
a) Pre-clinical trials, demonstrating range of activity against pathogens and nonpathogens, generation of resistance in vitro and in vivo (taking into account existing
resistances), appropriate dosing regimes for efficacy and minimising resistance,
including pharmacodynamic and pharmacokinetic data and models.
b) Clinical trials, to confirm the validity of pre-clinical data. Account should be taken of
clinical diversity in multi-centre trials, compliance with good clinical practice and
parameters for assessing efficacy of treatment.
7. Assessment of the potential of antimicrobials to select for resistance in the target
species, including:
a) concentrations of the active form in the intestines
b) routes and level of human exposure to resistant organisms
c) degree of cross-resistance within and between antimicrobial classes
d) pre-existing level of resistance in pathogens of human health concern, in both
humans and animals
8. Establishment of acceptable daily intake, maximum residue level and withdrawal
periods, taking into account effects of residues on human intestinal flora and methods for
testing residues.
9. Environmental impact assessment, aiming to minimise effects.
10. Establish a summary of the product characteristics, forming reference data for
labelling.
11. Post-marketing surveillance
a) existing pharmacovigilance
b) general epidemiological surveillance, according to OIE Terrestrial Code
c) specific surveillance of target pathogen, food borne pathogens and commensals
12. Supply and administration of veterinary antimicrobial agents. Ensuring that all
antimicrobials are prescribed by authorised persons, supplied via the authorised systems,
administered under veterinary supervision, and destroyed properly
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Annex 9: Final report Defra project OD2006
13. Control of advertising, ensuring it complies with the authorised use and is restricted to
authorised professionals according to national legislation
14. Training of antimicrobial users (including vets, pharmaceutical industry and animal
owners) in disease prevention and management, selection for resistance in foodproducing animals and observing responsible use recommendations.
15. Encouraging research
OIE: Responsibilities of the veterinary pharmaceutical industry in respect of
antimicrobials.
1. Marketing authorisation. Supply of quality information to regulatory authorities,
implementation of general and specific pharmacovigilance.
2. Marketing and export. Only market licensed and approved antimicrobials, through
licensed/authorised distribution systems. Certify quality for export.
3. Advertising. Advertise only within terms of licence and ensure that advertising directly to
food animal producers is discouraged.
4. Training, in responsible use of antimicrobials
5. Research
OIE: Responsibilities of veterinary wholesale and retail distributors in respect of
antimicrobials.
1. Supply. Only supply on prescription of vet or other authorised person
2. Records. Retailers should keep detailed records of supply
3. Training, in responsible use of antimicrobials
Annex 9.3: Possible additions to RUMA guidelines
A) Poultry
Role of antimicrobials


Every farm should be working in accordance with a written Preventative Medicine
Plan drawn up by the vet and farmer that emphasises practical measures towards
minimising antimicrobial usage on that farm
Consider other treatment options before using antimicrobials
Veterinary control and responsibilities
 Policies and protocols for the use of antimicrobials on each farm should be agreed
between vet and farmer. Deviations from this agreement require specific justification
 Importance of Continuing Professional Development for vets and farmers
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Annex 9: Final report Defra project OD2006
Farmers’ responsibilities
 Proper disposal of dead and dying stock
 Accurate information to vet, especially in respect of recurrent disease
 The administration of an accurate dose
 Attention to storage, expiry, withdrawal times and disposal of surplus antimicrobials in
accordance with written instructions from a veterinary surgeon
 Accurate records to be kept of all antimicrobial drugs purchased, used and disposed
of
 Illegal (UK) to use drugs that have not been prescribed by a veterinary surgeon
Indications for use
 Where an infectious agent, or agents, are known or strongly suspected to be present
and to be associated with the existing clinical problem
 Only when clinically relevant, e.g. not in uncomplicated viral conditions or in many
cases of salmonellosis
 Use in the absence of a specific infection requires clear justification
Diagnosis
 Health problems must be investigated at an early stage, including the use of postmortem examinations, microbiology and serology
 In the event of treatment failure or disease recurrence the appropriate diagnostic tests
and sensitivities must be repeated when embarking on second line treatment.
Culture and sensitivity testing
 Whenever possible ascertain the susceptibility of the infectious agent to the
antimicrobial before, or in parallel with, the start of its use
 Always establish sensitivity before changing antimicrobial, repeated use, off-label use,
or the use of an antimicrobial combination
 Maintain records on-farm and at veterinary practices of the results of sensitivity tests,
and refer to them when considering treatment options.
Use in treatment
 Limit treatment to affected flocks
Use in prevention
 Administering antimicrobials to birds in the first few days of life may enhance the
establishment of resistant bacteria in the immature gut flora and act to eliminate
antibiotic-sensitive bacteria from the flock throughout the whole of the growing period
until processing. Therefore, dosing chicks upon entry to the farm should be avoided
wherever possible. In some diseases, e.g. mushy chick disease and high mortality in
first week of life, it may be necessary.
 Limit flocks treated to those that are ill and at-risk, with justification needed for the risk
status of clinically unaffected birds
 No prophylactic use of fluoroquinolones
 There should be a written policy on prophylactic use for each farm and this should be
reviewed at least annually.
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Annex 9: Final report Defra project OD2006
Antimicrobial selection
 Two options:
 EITHER use narrowest-spectrum antimicrobial possible, considering agent,
product licences for species and indication, prevailing resistance patterns,
pharmacokinetics, mode of action, formulations available, routes of administration
and importance for human treatment.
 OR Dutch approach through the development of a formulary: detailed, prescriptive
list of 1st, 2nd, 3rd choice antimicrobials for 21 conditions, including some off-label
recommendations. Likely to produce most consistent usage on farms (if followed)
and based on detailed considerations by experts. May help vets resist pressures
to prescribe favourite/new/‘stronger’ antimicrobials. Deviations from list may be
necessary according to local resistance patterns. UK product licenses likely to lead
to significant differences from Dutch recommendations. Risk of over-use of a few
antimicrobials country-wide, and repeated use on insensitive organisms unless
frequent review of sensitivities is performed.
 Antimicrobials important in refractory human conditions (particularly fluoroquinolones
and extended-spectrum cephalosporins) only to be used for a short period with strict
justification. Absolute minimum use of fluoroquinolones
Off/extra-label use
 Illegal (UK) to use drugs not licensed in the UK for food-producing animals
 Culture and sensitivity testing of the agent required
 Strongly discourage off-label use of fluoroquinolones
 No use of drugs off-label for growth promotion or non-specific prophylaxis
Dosage/route/schedule/duration
 Sub-therapeutic dosing should not be practised
 Use best available data for doses and regimes to minimise resistance and review
available data regularly (this would logically be incorporated into a regularly-updated
formulary, if such an option were pursued)
 Vet should leave written instructions stating dose, intervals, duration, withdrawal
periods, storage conditions, recording, total drug to be used and instructions for
disposal of unused drugs
 Avoid oversupply of antimicrobials
Recording
 Vet to record diagnosis, reasons for any deviation from written policy, outcome and
any identified resistances
Monitoring
 Vet to monitor and record sensitivity trends as part of the records for each farm clients
 Report any decrease in sensitivity to SARS – suspect adverse reaction scheme run
by Veterinary Medicines Directorate
Long-term use of antimicrobials
 Regular reassessment of long-term use, including clinical efficacy and bacterial
sensitivities, by vet and farmer
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Annex 9: Final report Defra project OD2006
Other
 Minimise any environmental contamination by antimicrobials
B) Pig
Role of antimicrobials
 Every farm should be working in accordance with a written Preventative Medicine
Plan drawn up by the vet and farmer that emphasises practical measures towards
minimising antimicrobial usage on that farm
 Consider other treatment options before using antimicrobials
Veterinary control and responsibilities
 Policies and protocols for the use of antimicrobials on each farm should be agreed
between vet and farmer and reviewed at least annually. Deviations from this
agreement require specific justification
 Importance of Continuing Professional Development for vets and farmers
Farmers’ responsibilities
 Attention to storage, expiry, withdrawal times and disposal of surplus antimicrobials
 Maintain accurate records of drugs purchased, used and disposed of.
 Illegal (UK) to use drugs that have not been prescribed by a veterinary surgeon
 Only administer accurate doses of antimicrobials by the correct route in accordance
with written veterinary instructions.
Indications for use
 Where an infectious agent is known or strongly suspected to be present
 Only when clinically relevant, e.g. not in uncomplicated viral conditions
 Use in the absence of a specific infection requires clear justification
Diagnosis,
 Ideally, a specific diagnose should be sought and AM use should be based upon
accurate diagnostic information.
 Accurate diagnosis is especially important in the event of treatment failure, disease
recurrence, or if second-line treatment including combination or off-label use is being
contemplated
Culture and sensitivity testing
 Whenever possible ascertain the susceptibility of the infectious agent to the
antimicrobial, before, or in parallel with, the start of its use
 Routine sensitivity testing of target pathogens particularly recommended in intensive
units
 Always establish sensitivity before changing antimicrobial, repeated use, off-label use,
or the use of an antimicrobial combination
 Maintain records on-farm and at the veterinary practice of the results of sensitivity
tests, and refer to them when considering the choice of antimicrobial therapies
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Annex 9: Final report Defra project OD2006
Use in treatment
 Minimise number of animals treated
 Treatment of populations should be strategic, treating the fewest possible animals
either to protect vulnerable individuals or reduce excretion by infected stock
Use in prevention
 Minimise the number of animals treated, justifying use in respect of exposure to
infectious agent and immune status of animals
 No prophylactic use of fluoroquinolones
 There should be a written policy on prophylactic use for each farm
Antimicrobial selection
Two options:
 EITHER use narrowest-spectrum antimicrobial possible, considering agent, product
licences for species and indication, prevailing resistance patterns, pharmacokinetics,
mode of action, formulations available, routes of administration and importance for
human treatment
 OR Dutch approach: detailed, prescriptive list of 1st, 2nd, 3rd choice antimicrobials for
20 conditions, including some off-label recommendations. Likely to produce most
consistent usage on farms (if followed) and based on detailed considerations by
experts. May help vets resist pressures to prescribe favourite/new/‘stronger’
antimicrobials. Deviations from list may be necessary according to local resistance
patterns. UK product licenses likely to lead to significant differences from Dutch
recommendations.
 Antimicrobials important in refractory human conditions (particularly fluoroquinolones
and extended-spectrum cephalosporins) only to be used for a short period with strict
justification
Off/extra-label use
 Illegal (UK) to use drugs not licensed in the UK for food-producing animals
 Careful justification of use required
 Culture and sensitivity testing of the agent required
 No use of drugs off-label for growth promotion
Dosage/route/schedule/duration
 No sub-therapeutic dosing
 The therapeutic aim should be to achieve a clinically effective but not excessive
duration of treatment
 Vet should leave written instructions stating dose, intervals, duration, withdrawal
periods, storage conditions, recording, total drug to be used and method of disposing
of unused drug
 Avoid oversupply of antimicrobials
 Review the long-term use of antimicrobials annually or more frequently
Recording
 Vet to record diagnoses, reasons for any deviation from written policy, outcomes, any
identified resistances
 Such information to be held in the vet practice alongside other relevant information for
the farm, such as agreed drugs, withdrawal periods, sensitivity patterns
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Annex 9: Final report Defra project OD2006
Monitoring
 Vet to monitor and record sensitivity trends for each farm client
 Investigate any suspected increases in resistance
 Report any decrease in sensitivity to authorities
Long-term use of antimicrobials
 Written procedures for the regular reassessment of such use, by vet and farmer
Other
 Minimise any environmental contamination by antimicrobials.
19