main antibiotic used in poultry

Main antibiotic used in Poultry

It may classified
into:-

1. Synthesized

a. By bacteria
as Colistin & Bacitracin.

b. By Single
celled fungi as G-penicillin & 1^st generation of Cephalosporin.

2. Semi-synthetic as Aminopenicillins,
Amikacillin & doxycycline.

3. Totally synthetic as Quinelones , Sulphonamides
& Trimethoprim.

Targets and mode of action of
antibiotics

1.
The bacterial envelope (wall, cytoplasmic membrane).

The degradation or even the
partial disruption of the bacterial
envelope , weakness the bacterium and can leading to its bursting due to
the effect of the internal pressure as :

·
Betalactams (penicillin and
cephalosporin) inhibit the synthesis of cell wall when the organism divided.
(I.e. they active during the multiplication phase of the bacteria "Septicemic
–type infection").

·
Aminoglycosides (gentamycin , streptomycin ,
spectinomycin) and polypeptides (colistin) disrupt lipoprotein structure in
cytoplasmic membrane causing death of the micro-organism "this
bactericidal effect is active in case of chronic infections"

2. The
bacterial DNA

·
Sulphonamides and Trimethoprim block the synthesis of the
component elements of the DNA leading to inhibition of the micro-organism
multiplication "Bacteriostatic"

·
Qunelones block the replication and transcription of DNA lead to disruption of metabolism and rapid death of the micro-organism.

3. The components of protein
synthesis

·
Aminoglycosides induce
synthesis of abnormal protein leads to malfunction and death of the bacterium
"Bactericidal".

·
Macrolides
and Tetracyclins block
protein synthesis ,interfere with the
multiplication of the micro-organism without killing them
"Bacteriostatic"

According o the
type of action antibiotic can classified into

1. Bacteriostatic antibiotics:-

This activity obtained when an
antibiotic slow or inhibit the growth of the micro-organism, the main
Bacteriostatic antibiotics are: macrolides, Tetracyclins and Sulphonamides.

2. Bactericidal antibiotics:-

This activity obtained when an
antibiotic kill the micro-organism, the main bactericidal antibiotics are:
Aminoglycosides, Beta-lactams, Colistin, Quinolones and Trimethoprim
Sulphonamides combination.

According to the
spectrum of activity antibiotics can classified into

1. Broad spectrum antibiotics:-

Affect on Gram-positive and Gram-negative
micro-organisms as Tetracyclins.

2. Narrow spectrum antibiotics:-

Affect on Gram-positive only as
(Penicillins) or Gram-negative only as (aminoglycosides).

Combination of
antibiotics

The main advantage: is to increase the
antibacterial activity compared with the same molecules used in a single
therapy.

1. Enhancement of the activity of the
treatment.

·
By
broadening the spectrum

For examples:

i.
The combination of Colistin and Amoxicillin or Ampicillin in case of Clostridium
perfringens infection together with Enterobacteria in chickens.

ii.
Combination of Colistin and Spectinomycin in case of ORT infection
together with E.coli in Turkey.

·
By obtaining synergistic effect.

Mainly
used in case of immunosuppressed birds or when the infection located at a point
which the antibiotic cannot easily diffuse.

Note : Synergy is obtained with
each antibiotic being used at the dose at which it is normally administered.

For examples:

i.
Combination of Trimethoprim and Sulphonamides
or Beta-lactams and Aminoglycosides.

ii.
Colistin Flumequine combination on E.coli.

Toxicity of antibiotics

1. Direct
toxicity :-

a.
Hepatic toxicity.

This form
of toxicity is observed with antibiotics which undergo intense hepatic biotransformation
and / or intense elimination via the bile, such as the tetracyclines and
macrolides. Hepatic insufficiency increase the toxicity of these antibiotics
The long – term administration of chlorotetracycline (as feed supplement) can
cause hepatic and renal toxicity.

b.Renal toxicity

ý
With aminoglycosides and colistin (after parenteral
administration) this form of toxicity causes a functional modification of
nephrons with reduced ability to filter and increased albuminurea. However ,
the nephrotoxicity of aminoglycosides ,a lthough well documented in mammals ,
has not been studied in details in poultry , where if mainly affects ducks.

ý
With sulphonamides when the treatement continues for
several consecutive days , the sulphonamides, which are only slightly solube,
precipitate in the kidneys and ureters producing deposites which added to
urinary crystals. The water consuption falls, and is accompanied in layer in
drop in egg production and egg shell fragility. The water consumption must
therefore be monitored, and short – term treatment given (3 days) separated by
1 or 2 days when the treatment is not given.

c. Neuro – muscular toxicity

v
This can be observed with parenteral administration of
streptomycin, at a dose of 100 mg/kg (the usual dosage is 50 mg/kg/day as two
administrations). All species of bird appear to be affected. Turkey, duck,
pigeon, etc. It is expressed by curarizing effects (flaccid paralysis,
respiratory distress, and coma) and may lead to the death of the animal. These
symptoms appear within one hour of administering the product, and their
intensity is proportional to the dose. The pathogenesis of intoxication appears
to be due to Neuro-muscular blockage, attributed to the inhibition of the
release of acetyl-choline.

v
There is very limited oral toxicity associated with
short-term treatments, due to low levels of intestinal absorption.

Note:

i.
The nitrofurans, which have now banded in the
EEC, cause dangerous toxicity due to the production of active metabolites which
initiate chromosomal lesions. After administering a therapeutic dose to
chicken, ducks, and turkey, a dose dependant reduction in feed intake and
weight gain is observed. A supra therapeutic dose causes disorders of
reproduction function : testicular atrophy (young ducks and cocks) or delayed
******ual maturity (turkeys) in immature male poultry ; spermatogenesis disorders
(abnormal sperms, reduced motility) in adult poultry at dose over 100 ppm in
the feed for treatment lasting more than 10 days . In laying hens a reduction
is observed in egg weight, but with no effect on the laying curve as long as
the dose less than 200 ppm . The acute toxicity is expressed by
cardiomyopathies (mainly in turkey in cases of accidental over dosing) or
depression, with death without any warning signs.

ii.
Combining of 2 or 3 sulphonamides which
differing in rate of solubility , the toxicity reduced since the two
sulphonamides with different rates of elimination and solubility are less
dangerous than the double dose of either of the two ; this prevent the crystallizing
in the urinary tract. The S.pyridine, S.dimidin and S.diazine combination is
most commonly used for this purpose.

iii.
When two
nephrotoxic drugs are combined, the risks of intolerance or toxicity specific
to each antibiotic added together, and can even in some cases potentiate
for example colistin should not be injected into animals which are
concomitantly treatment I the form of trimethoprim-sulphonamides combination.

2. Indirect
toxicity of antibiotics :-

a.
Local intolerance

The
intolerance is caused by the irritant nature of the active ingredient and /or
the vehicles. After oral administration the intolerance is expressed by
irritation of gastric and intestinal mucosa (rare in poultry). after parenteral
administration (specially I/M rout) the intolerance expressed by an
inflammatory reaction of variable intensity : edema which develop into
sclerosis, abscess formation or necrosis. 5 to 10% drop in water consumption
observed after drug administration via oral rout.

b.
Incidents of microbial
origin.

§
Endotoxic shock : The bactericidal activity of the
antibiotic can be produce a sudden and massive lysis of bacteria, and
consequently the release of endotoxins contained in the bacterial wall. These
endotoxins cause hyperemia, tachycardia, tachypnoea and may lead to a
state of shock. This phenomena more
intense in beta-lactams, aminoglycosides, and quinolones.

§
Imbalance of intestinal flora : when administered
orally the antibiotic have non - selective effect on all sensitive bacteria in
the digestive flora , pathogenic or not. The imbalance created within this
population can encourage the proliferation of resistant micro-organisms, and
development of pathogenic micro-organism (Candidiasis in crop after treatment
with penicillin).

§
Deficiency of
vitamins B and K : vitamins B and K are
produced in poultry by the micro-organisms of gastrointestinal tract.
Insufficient synthesis occurs when antibiotic treatments are given for long
period (tetracyclines administered via feed).

c. Hypersensitivity

Anaphylactic shock (occur within minutes or
hour of administration) most likely to occur in poultry after parenteral
administration of an antibiotic. so it is advisable to inject 20 bird then to
wait for about 20 min. and to continue
only after checking that this group have not developed any specific signs.

Combination with anticoccidial agents and ionophore
growth promoters

Ionophore
anticoccidial agents often cause adverse reactions in poultry when they are
used at the same time as certain anti-infectives : in fact, the therapeutic
index of ionophores is often low and when it combined with other medicinal
products, their elimination can be inhibited , leading to abnormally high
concentrations and risks of intoxication by ionophores.

With tiamulin
and monensin whose clinical effects are particularly marked in turkey, it is
advisable:

*** To wait for at least 5 days after the last
administration of monensin before using tiamulin.

*** To wait for at least 1 day after the last
administration of tiamulin before distributing a feed supplemented with
monensin.

Ant-infective	Should not be used with	Clinical signs
[ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة]Oleandromycin (Macrolide) 2.2-4.2mg/kg [ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة]Tiamulin (250mg/l) [ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] Sulphonamides [ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] Sulphadimethoxine (500 ppm) Erythromycin 200 ppm [ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة]Furaltadone (200 mg/l) [ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة]Furazolidone 800 ppm [ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة]Furazolidone (200-400 ppm) [ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة]Chlortetracycline (30 ppm)	Monensin (ionophore antibiotic 80-100 ppm) Ionophore anbicoccidia (Monensin, narsin, salinomycin) Monensin 120ppm Lasalacid (125 ppm) Monensin (120 ppm) Lasalacid 125 ppm Monensin 120 ppm Monensin (120-240 ppm) Lasalacid (125-250 ppm) Amprolium (125 ppm) Clopidol (125 ppm)	Acutemyopathy of the feet muscles Reduced consumption, weight loss, muscular necrosis. Reversible lesions. Drop in yield, apathy, dose not resolve after the end of the treatment Drop in yield, apathy Apathy, drop in yield Loss of growth, reduced water consumption Excitation, drop in yield, reduced consumption Weight loss, balancing difficulties Anatomical and biochemical changes to the bones

[ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة]Dosage

The term
'dosage' converse not only the daily dose (expressed in mg or IU of active
ingredient per Kg of live weight) but also the administration regimen (duration
of each administration and interval between them), for a total duration which
is usually between 3 and 5 days).

1. determining
the dosage:-

§
The dosage must be sufficient to reduce the bacterial
population to a size which is small enough to be destroyed by the animal's
immune defense system. According to classical pharmacology, the optimal dosage
is the dosage which ensured that the tissue concentrations achieved for the
entire duration of interval between any two administrations are maintained at a
level which is greater than MIC of the targeted micro-organism. If a
bactericidal antibiotherapy is required, the objectives are higher, and
attempts should be made to attain concentrations near to the MBC.

§
The dosage indicated by the manufacturer is the one
which was proved to be efficacious in the proposed indications and then
validated by the Marketing Legal Authorization in these indications. However
the dosage is not fixed, for many reasons linked to the progress of
pharmacology science , changes in legal requirements , evolution of microbial
sensitivity. The veterinarian must know how to adapt the dosage, if required,
based on the information eventually available: MIC, tissue concentrations, dose
or time dependant mode of action of antibiotic, etc. The tissue and serum
concentrations classically attained by the antibiotic are compared with the MIC
obtained in vitro for the isolated strain.

§
The dosage is expressed in milligrams or international
units (colistin, gentamycin, spiramycin, etc), of active ingredient per Kg body weight per day.

2. Adjusting
the dosage to suit the type of antibacterial action:-

·
For bacteriostatic or bactericidal time-dependent
antibiotic.(penicillin, cephalosporins, macrolides & related molecules and
fluroquinelones 'on Gram positive micro-organisms'), the optimum therapy is
provided by achieving the longest possible contact time, at a concentration
above the MIC, between the antibiotic and the bacterium. Consequently, there
advantages to giving continuous administration via the feed or via the water
using dosing pump. Continuous lighting favors this type of therapeutic regimen.

·
For dose dependant antibiotics (amoxicillin,
aminoglycosides, fluroquinelones on Gram negative micro-organism), however the
highest possible dose should be administered so as to obtain concentrations
rapidly, and with lower administration frequency (pulsed administration): the
extreme example is parenteral administration. when administering via drinking
water , the product should be given for 3 – 6 hours per day, and with due to
consideration given to the fact that the first hour of the day are when the water consumption
reach it highest and that sicker birds require
longer daily treatment periods 6 – 8 hours, to cater for their reduced
rate of water consumption.

3. Treatment
duration

Three to
five days are generally recommended when treating an infection. This is a very
short period especially in view of general maxim for effective antibiotherapy
(strike quickly , strike hard and for a long time).

A
longer duration may be required when:-

i. The MIC of
the causative micro-organism is close to the tissue and serum concentration.

ii. The
antibiotic cannot easily access the site of infection, e.g. in mucus of
respiratory tract (infections due to Paseurella.), or in joint (infections due
to staphylococcus- aureus).

iii. In case of
chronic infection (presence of fibrin, pus or absence of vascularization).

iv. When the
objective is eradicating the Mycoplasma or Salmonella infection in breeder,
treatment period of 10 days to several weeks these bacteria are difficult to
eliminate due to these organisms are located intracellular).

Reducing the treatment duration hazardous:-

Increases
the risks of relapse and the transition to chronic state.

Risks and limits to antibiotherapy for layers and
breeders

1. Risks on
egg production

The
administration of antibiotics via drinking water can cause a slight reduction
in egg yield, ad often following on from an insufficient consumption of water.
For breeders, more eggs are laid on the ground and the percentages of eggs that
can not be incubated are rise (due to deformation, discoloration, and
granulation). This phenomenon is observed when sulphonamide treatments given
via the feed above a dose of 500 ppm, or occasionally with quinelones in
breeder turkeys.

2. High
demand on the liver.

Hepatic
insufficiency frequently occurs after peak of laying, particularly in the
second half of the laying period. Since antibiotics are primarily metabolized
by the liver, this organ should be protected by giving birds the appropriate
nutritional supplements (lipotropic, choleretic or cholagogue factors) after
the treatment.

3. Risk of
inducing antibioresistance in the offspring.

The
bacteria in the gastrointestinal tract which come into contact with the
antibiotic when treating breeders are readily found on the surface of eggshells
when they are laid. The resistant strains are thus easily spread amongst the
chicks.

Analysis of therapeutic failure

1. What's the
therapeutic failure?

a.In clinical terms.

The
treatment did not improve the symptoms

·
Intolerance reaction to the treatment.

·
No improvement in the clinical condition.

·
Improvement, but transition to a chronic condition.

·
Cure followed by a relapse shortly after.

b. In
bacteriology term.

The
aim of the treatment was not to treat a disease but to eliminate bacterial
carriage: in this case a failure is declared if the micro-organism are
re-isolated a few weeks after treatment. The animals continue to be
asymptomatic carrier. And build up a reservoir of the micro-organism which may
then trigger a future clinical outbreak in the same grow-out, or contaminate
the offspring (or eggs) in the case breeders or layers.

c. In
economic terms.

The
condemnation of the production may be the result of the lesion caused by the
infection, lesions at the site of injection, or the presence of residues in the
tissues and / or the production (eggs).

.

2. Possible
causes of therapeutic failure.

a. Erroneous
or incomplete diagnosis:-

·
Errors relating to the etiology :

-
Non-infectious aetiology.

-
Bacterial aetiology, where the bacterial component is
aggravated by environmental factors.

-
Multi-factorial aetiology, where the bacterial
component is aggravated by environmental factors (air, water) and / or
nutritional factors which were not thought to be significant.

-
Simultaneous presence of Mycoplasma and / or viruses
which aggravated the condition.

·
Incorrect interpretation of the antibiogram.

-
The bacteriological examination was carried put too
early: the pathogenic flora was not sufficiently well developed at that time to
be isolated by routine techniques.

-
Poor isolation techniques: media insufficiently
enriched which did not allow the incriminated micro-organism to grow, pollution
at the instant when the sample was taken or at seeding.

-
Poor seeding techniques: pollution by micro-organisms
from internal abdominal organs.

i.
The isolated bacterium is only partly
responsible for the disorders: it is an opportunistic micro-organism.

ii.
The isolated micro-organism is responsible for
the disorders, however, the antibiogram is invalid (the disks poorly preserved)
or was incorrectly interpreted (incorrect reading of inhibition diameter, MIC
too close to the critical concentration, etc).

b. Incorrect
practical implementation of the antibiotherapy:-

i.
Non-respect of the dosage: calculation errors,
incorrect estimation of water consumption, the live body weight not taken in
consideration, interval between administrations is too long, or the treatment
duration is too short.

ii.
Insolubility
of the treatment : use of
insufficient soluble products, non-respect of the dissolving orders (mixing
orders, temperature of the stock solution), problems of compatibility between
medicinal products, with the water itself (pH, hardness), deficient maintenance
of the pipe work (lime scaling, biofilm, rust, leaks, etc).

iii.
Insufficient treatment intake: Insufficient
number of drinkers, located too high up, incorrectly arranged in building or in
poor condition: Blocked or leaked, or water supply cut off.

c. Inefficacy
of the antibiotic in the animal.

i. Antibiotic
not suited to the causative micro-organism, in terms of its spectrum or ability
to diffuse through the tissues.

ii.
Interactions between the medicinal products:
antagonism of the mode of action (combination of a bacteriostatic with a
bactericidal which is active only on micro-organisms in their active
multiplication phase), Toxicological risk (tiamulin-monensin).

iii.
Obstacles preventing the antibiotic from
reaching the site of infection: by an abscesses or natural physiological
barriers (eye, CSF, etc) insufficient vascularization (fibrin, necrosis),
inactivation at the site of infection (acidic pH, pus, anaerobiosis).

iv.
Site of
infection reached , but the MIC is too high and/or the antibiotic
concentrations are too low.

v.
Immune suppressed animals whose immune defense
cannot finish off the remaining micro-organisms once the antibiotherapy has
ended.

Methods for
administration of antibiotics

Method	Advantages	Disadvantages
Drinking water	¨ Easy ¨ Allow rapid reaction in emergency. ¨ The product acts quickly, immediately reach the site of absorption. ¨ Dosage flexibility (double dose attack can be given followed by normal dose). ¨ Animals which have lost their appetite generally continue to drink. ¨ Well suited to products which have dose- dependant action.	¨ The water consumption must be controlled. ¨ Some products suffer from solubility related problems (esp. sulphonamide in acidic water). ¨ Risk of water consumption reduction. ¨ Some of the product may be lost with certain species (wastage with ducks) or due to defective equipment (leakage). ¨ Specific installation is required (dosing pump).
Feed	¨ Substances which are not soluble can be used. ¨ No preparation required on the farm. ¨ Offers benefits for preventive long-term treatments, or as a complement to curative treatments initiated via the drinking water. ¨ The birds appetite and water consumption are not affected as much as with an administration via the water.	¨ Difficult to react quickly to an emergency. ¨ Risks of under dose. ¨ Not well suited to molecules which have dose-dependant action. ¨ Only suitable for subjects which have not lost their appetite. ¨ The active ingredient may interact with the feed (chelating, inactivation) , or be inactivated by heat process. ¨ Specific instillation is required. (double silo).
Injection 1 - S/C 2 – I/M	¨ The administration dose can be matched to the live body weight. ¨ Quickly acting. (first line treatments) ¨ Antibiotics which are poorly absorbed can be used. (colistin, amino-glycosides) ¨ Can be used in treatment of badly affected animals which are no longer eating.	¨ Only few preparation are specifically for poultry. ¨ Problem to determine the withdrawal period. ¨ Suspensions and oily solutions are difficult to be injected. ¨ Risk of irritation, necrosis, and abscesses formation (tetracycline, Sulphonamide) ¨ Stress of handling. ¨ Risk of endotoxic shock. ¨ The product is eliminated rapidly so the re-administration is required with 24 to 48 hours. ¨ High labour cost.
Injection 1 - S/C 2 – I/M	¨ The injection sites have a low economic value (small impact in the event of this meat being condemned. ¨ Easy to performed. ¨ Rapid resorption than S/C route	¨ Technically difficult. ¨ High risk of self injection. ¨ Risk of residues in site of injectionand condemnation of meat. ¨ Danger of damaging nerves and tendons when injected in the thigh.

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