Antimicrobial Final

Antimicrobials
Aim of medication Prevention of some important poultry disease:
Prophylactic medication is usually used in the poultry practice

to prevent or reduce the incidence and severity of some
important poultry diseases to which the birds are likely to be at
risk in the future.
- The prophylactic medication may be used continuously or for
a certain period of time.
- In the prophylactic medication, the withdrawal time should be
considered before the collection of the poultry products for the
human consumption.
Basics of antimicrobial therapy
Antimicrobials
The prophylactic medication includes:
1-In feed use of certain macrolides especially the tylosin in the feeds
2-In feed use of different anticoccidial drugs e.g. ionophores, clopidol

and diclazuril in the feeds of chicken
In feed use of Amprolium in the feeds of chicken and turkeys to prevent
or reduce the incidence and severity of coccidiosis through setting up of
immunity by trickle infection or step down program.

Antimicrobials
3-In feed use of certain anti-clostridial drugs e.g. lincosamides,
streptomycin, certain probiotics,
4-In feed use of certain antibiotic e.g. chlortetracycline and
oxytetracycline in the feed of chicken, ducks and turkeys to prevent or
reduce the incidence and severity of E.coli infections and fowl cholera.
5-In feed use of different anti-mycotoxins drugs

6-In feed use of different organic acids in the feeds of chicken and turkeys
to prevent or reduce the incidence and severity of salmonellosis and
fungal infections.
Antimicrobials
B-Treatment of serious treatable diseases:
From the medication point of view, poultry diseases are classified into
three groups, they are:
Non-treatable diseases: The non-treatable poultry diseases are limited
number of diseases and include avian tuberculosis, avian
pseudotuberculosis, avian toxoplasmosis, and avian cryptosporidiosis.
Non-treatable diseases but can be dealt with: as the viral respiratory and
enteric diseases in which the different types of antibiotics can be used to
control the secondary bacterial invasions.

Antimicrobials
C-Improvement of bird's performance:
The medication is sometimes used to enhance the bird's performance e.g.
1-In feed use of certain medicinal products (AGPs) to improve the weight
gain, decrease the feed conversion rate and to increase the feed efficiency
and egg production
2-In feed use of the active dry yeast "Saccharomyces cerevisiae" and other
probiotics (Lactobacillus acidophilus) to improve the weight gain, feed
efficiency, egg production and chick quality.
3-In feed use of the sodium and calcium butyrate to improve the weight
gain, feed efficiency, egg production and chick quality.
Antimicrobials
D-Anti-stress medication:
The stress is defined as the adverse factors to which the birds are exposed and to
reduce the resistance of the affected birds to different infections.
Avian species are usually suffered from multiple types of stressors which include the
transportation, frequent handling, the high ambient temperature, the extreme cold,
post-vaccinations, severe chronic parasitism, frequent noise and over-crowding.
Anti-stress medication is usually applied before, during and/or after the period of
stress to reduce the effects of infections which may result from the reduced resistance.
This anti-stress medication includes multi-vitamins + amino acids + multi-minerals +
antibiotics as tetracycline.
Such anti-stress medication helps to reduce the effects of stress especially where sub-
optimal nutrition is present.
Antimicrobials
From ancient to the future

Penicillin flehming  Bleomycin and anthracycline

Antimicrobials
D igestive flora
Time – types –Location-

Crop & Gizzard
Duodenum & Ileum: 100,000,000 micoroganism /g (small number)
Cecum: the largest count: 100 billions, 200 types, 50 spp.
Clostridium, Eubacterium, peptostreptococcus, Bifidobacterium, bacteriods)
R espiratory flora: trachea 10 000 times less than 1 gram of GIT(102-105)

Types : Gram positive: Micrococcus, Streptococcus, Lactobacillus & Corynebacterium
Gram negative: Pasteurella & Enterobacteriaceae (after 5th week)
Antimicrobials
Medication is mandatory even in presence of immune
system due to:
1- Immune suppression (Under stress)

2- Microbial evasion

Antimicrobials
Definition
 Antimicrobials include:
 Antibiotics – chemical substances produced by bacteria or fungi that
kill or inhibit bacteria at low concentrations
 Semisynthetic
Aminopenicillin – doxycycline – clindamycin
 Antibacterials: completely synthetic chemical substances: many

antibacterials and all
 Sulfonamide – Quinolones- Imidazole – Nitofuran

Antimicrobials
Information No. 1
The success of antimicrobial therapy depends upon many interacting factors,

1- Pharmacodynamics (drug interaction with the pathogen)
2- Pharmacokinetics (drug absorption, distribution, excretion)
3- the components of the host immune system
Basics ofBasics of antimicrobial

antimicrobial therapy therapy Hossam Mahmoud , B.V.Sc, M.V.Sc, Ph.D.
MIC
Information No. 2
T1/2
MIC
MBC (never to eliminate )
OBC

MIC
Information No. 2
The activity of an antimicrobial agent against a particular

microbe is often expressed as the minimal inhibitory
concentration (MIC).
Minimal Inhibitory Concentration (MIC) of the drug needed to
kill the bacteria is too high to achieve safe therapeutic levels in
the patient .
• Small zone of inhibition on the agar disc diffusion test used to
test susceptibility of bacteria to antibiotics
MIC
Information No. 3
AUC
Vd
Cmax
Tmax
Therapeutic index

MIC
Information No. 3

Antimicrobials
Information No. 4
When interpreting antimicrobial susceptibility information, the poultry veterinarian
must keep in mind that this is an in vitro test that does not take into consideration:
1- The drug can reach the site of infection

2- Whether the drug is bacteriostatic or bactericidal for the microbe.
3- Mixed infection, It should also be remembered that the MIC is usually
performed by the laboratory on only one isolate, many infections of poultry are
secondary, so a “sick flock” is often affected by multiple isolates that can have a
wide range of MICs.
4- MIC breakpoint criteria in veterinary medicine are not uniform worldwide and
are often based on standards for human medicine
Antimicrobials
Information No. 6
NB: pharmacokinetic data determined in mammals are not always
applicable to poultry because :
birds have higher body temperatures
higher metabolic rates and Faster elimination half-life times for
medications.
and shorter alimentary tracts,
This frequently leaves the poultry veterinarian with an antimicrobial

therapy decision based upon clinical judgment from previous cases
rather than on the uncertain available science.
Antimicrobials
Information No. 7
The primary criterion for measuring success of treatment under

poultry industry conditions is:
1- Reduction of morbidity and mortality.

2- Return to regular water and feed consumption
3- Normal growth rate, and normal egg production

Antimicrobials
Information No. 8
Antibiotics as AGP
1. Stimulation of intestinal synthesis of vitamins by bacteria.
2. Bacterial related activity :
Reduce :total number, harmful, deamination, urease, cholyltaurine
hydrolase
1. Reduction in total numbers of bacteria in the intestinal tract
2. Inhibition of harmful bacteria
3. Inhibition of bacterial deamination and decarboxylation of AA
4. Inhibition of bacterial urease.
5. Improved energy efficiency of the gut.
Antimicrobials
Information No. 8
7. Nutrient sparing.
8- Reduced the outputs of environmentally important greenhouse gases
and nutrients such as nitrogen and phosphorus.
8. Improved nutrient absorption
9. Modification of intestinal enzyme activity.
10. Reduced immune stimulation
11. Anti-inflammatory effects on intestinal cells.

Philosophy of Antimicrobials
Information No. 9
 Antimicrobial therapy involves a calculated risk that

selective toxicity of the drug for the microorganism
will occur before any toxic effect of the drug on the
host.

Information No. 10
 The aim of antimicrobial therapy is to assist the

host’s defense mechanisms in containing and
eliminating the invading microorganism(s).
 The ability to do this is enhanced when:
 therapeutic drug concentrations are rapidly
produced at the site of infection maintained for
sufficient length of time.
Information No. 10
 In doing so the pathogen’s ability to:

 Replicate is reduced or eliminated,
 Decreasing the production of toxic substances, both
from the host and the pathogen.
 The overall result is elimination of the infection with

a decrease in the disruption of function of adjacent
tissues and acceleration of the host’s return to health
How to select Antimicrobials
Microorganism
Pharmacodynamics
MIC MBC MPC
Cost Pharmacodynamic Time or conc. Dependent
Cost of treatment First pass effect
Value of animal PAE
Information No. 11
Risk
Direct host toxicity Pharmacokinetics
Adverse drug interaction Route of administration
Destruction of normal flora Physicochemical properties
Promotion of drug resistance Distribution and elimination
Impairment of host defense Characteristics of the drug

Selection of appropriate antibiotic
• Microrganisms
• Drug Pharmacokinetics
• Mechanism of action
• Distribution in blood and tissues
• Route of elimination
• Bactericidal vs. Bacteriostatic
• Resistance
• Toxicity
• Convenience of administration
• Availability
• Cost Basics ofBasics of antimicrobial
Bio-availability ORAL drug
Information No. 12
 Systemic availability is influenced by the stability of an

antimicrobial agent in the highly acidic gastric contents (pH 3–4)

 Since absorption takes place by passive diffusion across the mucosal
epithelial barrier, high solubility in lipid is an important property.
 Having passed through the mucosal barrier, drug molecules are
conveyed in hepatic portal venous blood to the liver, the major
organ of drug metabolism, prior to reaching the systemic ( general)
circulation.

Information No. 12
 Presystemic metabolism, referred to as the first-pass effect, can

occur in the gut lumen or mucosal epithelium or, most importantly, in
the liver
 The first-pass effect decreases the systemic availability of drugs that

undergo extensive hepatic metabolism.
 Presystemic metabolism activates p. Metabolic conversion (N-

dealkylation) of enrofloxacin to ciprofloxacin
 difloxacin to sarafloxacin is likely to occur
Information No. 12
 The systemic availability of aminoglycoside antibiotics, which are
polar organic bases, is very low following oral administration, whereas
they are rapidly absorbed and completely available systemically when
administered by IM or SC injection.
 It is the absorption process that differs between the gastrointestinal tract
and parenteral sites
 Examples of lipophilic antimicrobial agents include

fluoroquinolones, macrolides and lincosamides, doxycycline,
trimethoprim, metronidazole and chloramphenicol.

F Antibiotic / Antibacterial F Antibiotic / Antibacterial
70-50 OTC 80-70 AMOXY
50-40 CTC 50-40 AMPICILLIN
80-70 DOXY 5 AMINOGLYCOSIDE
90 ENRO 5 AMINOCYCLITIOL
90 CIPRO 75 ERYTHRO
90 DANO 80-70 TYLOSIN
90-80 FLUMEQUINE 70-60 SPIRAMYCIN
90 NOR 100-90 JOSAMYCIIN
90 BIFLOXACINE 80-70 TILIMICOSINE
100-90 OXOLINIC 70-60 TIAMULIN
60-50 NALDIXIC 90-80 SULFADIMIDINE
50-30 FURALTIDONE 50 SULFAQUINOXALINE
80 METRONIDAZOLE 90 SULFA + TRI
Bio-availability
Information No. 13
 While absorption from parenteral sites is mainly controlled by

capillary blood flow at the absorptive surface

Bio-availability
Information No. 14
 Selective binding to a tissue component
e.g., Aminoglycosides to phospholipid-rich tissues of the inner ear and

kidney cortex) may account for only a small fraction of the amount of drug
in the body but could produce an adverse, even toxic, effect or the residue
could limit the use of the drug in food-producing animals
 Some of these drugs (Erythromycin, clindamycin, doxycycline) bind

extensively to plasma proteins, which limits their availability for
extravascular distribution.
 Clindamycin, attain effective concentrations in bone.
BBB
Information No. 15
Of the lipophilic antimicrobials, only certain individual drugs penetrate

the blood-brain and blood-CSF barriers and attain effective
concentrations in cerebrospinal fluid
(e.g., Cefotaxime, ciprofloxacine, sulfamethoxazole, trimethoprim,
metronidazole, chloramphenicol).
 In the presence of meningitis, most intravenously administered third

generation cephalosporins (except cefoperazone) penetrate the blood-
CSF barrier

Absorption
Information No. 15
Gut absorbed Antibiotics

Aminopenicllin
Tertracyclines
Lincosamides
Chloramphenicol
Quinolones
Metronidazole
All sulfonamides except sulfaclozine and sulfaguanidine

Absorption
Information No. 15
Gut non absorbed Antibiotics

Aminoglycoside
Aminocyclitol
Polypeptide
Sulfaguanidine and sulfaclozine

Excretion
Information No. 15
Dropping
Non absorbed
Aminoglycoside
Aminocyclitol
Polypeptide
Sulfaguanidine and sulfaclozine

Excretion
Information No. 15
Urine (kidney)
Amoxycillin (Not ampicillin)

Cephalosporins
Tetracyclines (Not doxycyclines)

Excretion
Information No. 15
Bile (enterohepatic circulation)
Macrolides
Lincosamides

Excretion
Information No. 15
Skin
Macrolides
Lincosamides
Tetracyclines

Sensitivity
Information No. 16
Comparison between two types of data:

MIC & pharmacokinetic
1- Sensitive: site conc. > MIC

2- Intermediate: =
3- Resistant: site conc. < MIC

Spectrum
Information No. 16
Natural and Clinical spectrum
Some antibacterial drugs are considered narrows spectrum in that they
inhibit only Gram-positive or Gram-negative bacteria,
whereas broad-spectrum drugs inhibit both Gram-positive and Gram-

negative bacteria.
However, this distinction is not always absolute, as some agents may be

primarily active against Gram-positive bacteria but will also inhibit some
Gram-negatives
Spectrum
Information No. 16
 Broad spectrum
 Aminopenicillin – cephalosporins – chloramphenicol –
tetracycline
 Sulfa+trimethoprim – Quiolones
 Narrow
Aminocyclitol- Aminoglycoside- Macrolides-
Lincosamide- Polypeptids- Sulfonamide
Spectrum
Broad spectrum Narrow spectrum (Act on either Gram +ve or –ve
Act on both Gram +ve and -ve Gram -ve pathogens Gram +ve pathogens
Aminopenicilins Aminoglycosoides "aerobic" Narrow spectrum penicilins
The 2nd and 3rd generation cephalosoprins The 3rd generation cephalosoprins The 1st generation cephalosoprins
Phenicol group The 1st and 2nd generation of
Macrolides and lincosamides
Florphenicol quinolones
Tetracycline Aminocyclitol "aerobic" Pleuromutilin
Sulfa + trimethoprim Colistin sulphate Rifampicin
Lincomycin + spectinomycin Trimethoprime Metrobidazole "anaerobic"
Clindamycin + spectinomycin Nitrofurans Bacitracine
The 3rd and 4th generation of quinolones -- Fosfomycine
Tylosin + doxycycline -- Glycopeptides "Vancomycin"
Tiamulin + chlorotetracyclin -- Sulfa drugs "aerobic bacteria"
Bacteriostatic or Bactericidal
Information No. 17
Antimicrobials are usually regarded as bactericidal if the

MBC is no more than 4 times the MIC.
Static: when C less than control but higher than original

Cidal: when less than original
No antibiotic completely eliminate the infection
It is always the immune system which finish it
Information No. 17
Bacteriosatatic Bactericidal
Aminocyclitols Penicllins
Tetracyclines Cephalosporins
Macrolides Aminoglycoside
Lincosamides Polypeptids
Chloramphenicol Quinolones
Sulfonamides Sulfa + Trimethoprim
Trimethoprim Linco + spectinomycin
Immune dependent. Immune independent
Concentration dependent
Duration dependent.
Pulse dose
Information No. 17
The Antibiotic which inhibit the growth of bacteria
Immune dependent antibiotics

Macrolide (exception)
Aminocyclitol (exception)
Chloramphenicol
Tetracyclines (exception)
Lincosamide
Sulfonamide
Information No. 17
The Antibiotic which kill the bacteria
Immune in-dependent antibiotics
Penicillins (only active)
Cephalosporins (only active)
Floroquinolones
Aminoglycosides
Metronidazole
Polypeptides
Sulfonamide +trimethoprim
Information No. 17
Exception
Tylosin and Erythromycin on Staph & strept.

Tetracycline on E. coli and Staphylococcus
Spectinomycin on Pasteurella

Information No. 18
Antimicrobial agents are often classified as exerting either:

Time-dependent
The most significant factor determining the efficacy of :
 Beta-lactams
 Macrolide
 Tetracyclines
 trimethoprim-sulfonamide combinations,
 chloramphenicol
is the length of time that serum concentrations exceed the MIC of a given
pathogen (time dependent)
Information No. 18
Increasing the concentration of the drug several-fold above the MIC does not
significantly increase the rate of microbial killing.
Rather, it is the length of time that bacteria are exposed to concentrations of

these drugs above the MIC that dictates their rate of killing.
Optimal dosing of such antimicrobial agents involves frequent administration

MIC
Prophylactic Sub therapeutic

prevention growth promotion
1 hour 10 hours
MIC Therapeutic
1 hour 10 hours time

Conc. Dependent
Information No. 19
. Other antimicrobial agents such as :

 Aminoglycosides
 Fluoroquinolones,
 Metronidazole
 Colistin
exert concentration-dependent killing characteristics.

Conc. Dependent
Information No. 19
Their rate of killing increases as the drug concentration

increases above the MIC for the pathogen and it is not
necessary or even beneficial to maintain drug levels
above the MIC between doses.
Thus, optimal dosing of aminoglycosides and
fluoroquinolones involves administration of high doses
at long dosing intervals (pulsed dose)

Important notes
Information No. 20
. Administration via the drinking water is usually preferable because sick
birds will tend to drink when they will not eat.
However, fluid intake by the birds may vary due to the :

• Weather,
• to the ease of access or hygiene of drinking water dispensers
(‘drinkers’)
• or to the unpalatability of the medicated water.
Care must be taken that the medication does not block the water system.

Important notes
Information No. 21
Water contamination and hygiene problems may arise as a result of poor

mixing and preparation, or from fungal proliferation in certain glucose-
containing carriers present in the formulation.
Drinker lines should be sanitized before drug incorporation and especially

after drugs in a sucrose or similar basis have been used.
They should be cleaned regularly as part of the routine terminal house

disinfection
HOW TO CALCULATE THE DOSE
Information No. 22
The most accurate method is to calculate the dose based upon the
total body weight of birds in the house, and then include that dose in
the volume of water or feed the birds are expected to consume
during each dosing interval.

HOW TO CALCULATE THE DOSE
Information No. 23
The drawbacks of dosing based on water consumption

1- Result in a toxic overdose if the ambient temperature increases, or the
amount of drug consumed may drop below the MIC of the bacteria being
treated if the ambient temperature declines
2- the Age Dosing at a constant rate per liter of drinking water can result in
overdosing of young chicks or under dosing of older birds.
3- Production purpose , hens producing eggs will drink more per unit of
weight than non- laying hens

PULSED DOSE
Information No. 24
A short, intensive treatment with certain antimicrobials may be administered

as a pulse dose
This method should only be used with:
1- Bactericidal antimicrobials
2- those with a wide margin of safety.
3- Conc. Dependent antibiotics
Pulse dosing requires that all of the medication to be administered for a 24-
hour period is mixed into the water the birds will consume 8 hours
In feed or water
Information No. 25
Alternatively, the feed may be medicated. This is convenient for the

farmer but it may take time getting feed mixed at the mill and mills may
find making special mixes uneconomical.
Absorption of the drug may be unpredictable because of binding to

feed ingredients.
Because sick birds will tend to drink when they will not eat So Some
birds may have a reduced feed intake and may require adjustment of
the drug concentration in their feed.
Rapid decision
Information No. 26
If possible, the first stage in the decision process is antimicrobial sensitivity tests.
In cases of high mortality, it may be necessary to medicate using the drug most likely to
be effective, while awaiting laboratory results.
Further medication can then be adjusted in the light of these results.
In addition, other factors such as ease of use of the product may be of significance,
especially in relation to the management system in operation. ‘
For example, for birds on a nipple line water system it is essential that a highly
soluble product is used to prevent blockage of the water system.

Take care from nipple system
Information No. 27
For birds on a nipple line water system it is essential that a highly

soluble product is used to prevent blockage of the water system.

Some well known uses
Information No. 28
Amoxicillin and ampicillin are active against Gram-positive micro-organisms and is
the drug of choice in clostridial enterotoxaemia of broilers and turkeys.
Neomycin are not absorbed from the gastro-intestinal tract.
Tylosin attains high bone levels and is reported to be effective in cases of osteomyelitis
associated with femoral head necrosis.
Florfenicol, Sulfaquinoxaline and enrofloxacin appear especially effective against

Pasteurella infections
. Tylosin, tilmicosin, tiamulin, and enrofloxacin have specific activity against
Mycoplasma
. Basics ofBasics of antimicrobial
Toxic combination
Information No. 29
Anticoccidials such as monensin, narasin, or salinomycin

should not be administered concurrently with tiamulin as toxic
effects are often fatal
.
Erythromycin and sulphonamides have also been reported to
cause toxic effects when administered with monensin.

Importance of Drug-Drug interaction
Information No. 30
 1- Combination to increase Drug Efficacy:
 • Sulfonamide + Trimethoprim
 • Tylosin + Doxycycline
 • Amprolium + Ethopabate
 • Lincomycin + Spectinomycin
 • Amprolium + Sulpha
 • sulfonamide + Pyrimethamine or Diaveridine

Information No. 31
2) To Broader the Drug Spectrum

• Doxycycline + Colistin
+ Gentamicin
+ Tylosin
• Amoxycillin + Colistin
• Oxytetracycline + Neomycin

Information No. 31
To Minimize the Drug Toxicity

• Sulphonamide + Trimethoprim

Information No. 32
4) To Avoid Drug Resistance

• Kitassamicin + Amoxycillin
Complete death to bacteria

Information No. 33
5) To Potentiate of the Action of a drug by another not related

• Ampicillin or Amoxicillin + Clavulanic acid

Information No. 34
6) To treatment of Complex diseases (CRD)

• Macrolides Aminoglycosides
Tylosin Gentamicin
Erythromycin Kanamycin
Spiramycin Streptomycin

Mode of Action on Bacterial structure
Information No. 34
• Direct Vs Indirect effect of Antibiotics
• PAE
Aminoglycoside, Tetracycline & Macrolides
• Inhibits adhesion and toxin production
All which inhibits protein synthesis
• Immune modulation
Basics of antimicrobial therapy Hossam Mahmoud , B.V.Sc, M.V.Sc, Ph.D.

Mode of Action on Bacterial structure
Information No. 34
Cell wall •
Gram positive •
Gram negative •
.Wall less bacteria •

Information No. 34
• Cell membrane
• Cytoplasm
• Ribosomes
• Nucleus (not in bacteria)

MECHANISMS OF ACTION OF ANTIMICROBIAL DRUGS
Information No. 35
Inhibition of cell wall synthesis –

Damage to cell membrane function –
Inhibition of protein synthesis –
 Inhibition of nucleic acid synthesis –
Inhibition of metabolic pathways –

Classification OF ANTIMICROBIAL DRUGS
Penicillins Aminoglycoside
Tertracycline
Narrow spectrum Streptomycin
Tetracycline
Semisynthetic Neomycin
Oxytetracycline
Extended spectrum Gentamycin
Doxycycline
Cephalosporins Aminocyclitol
Lincosamide
1st generation Spectinomycin
Lincomycin
2nd generation Apramycin
Clindamycin
3rd generation Macrolides
Polypeptide
Chloramphenicol Erythromycin
Spiramycin Colistin
Chloramphenicol Tylosin Bacitracin
florfenicol Tylvalosisn Fosfomycin
Thiamphenicol Kitassamycin Glycopeptide
Classification OF ANTIMICROBIAL DRUGS
Pleuromutilin Sulfonamide Nitrofuran
Tiamulim Sulfadimidine Furazolidone
Sulfaguanidine Furaltidone
Lincosamide Nitrofurantoin
Sulfaquinoxaline
Lincomycin
Sulfaclozine Ionophores ,
Clindamycin
Polypetide Quinolones Salinomycin
1st generations Lasalocid
Colistin
2nd generation Narasin
Bacitracin
Fosfomycin 3rd generations Nitroimidazole,
Glycopeptide 4th generation Metronidazole
MECHANISMS OF ACTION OF ANTIMICROBIAL DRUGS
Information No. 35

Inhibition of Cell wall synthesis
Information No. 36/1
–Selective
Bacteria cell wall unique in construction
• Contains peptidoglycan
Antimicrobials that interfere with the synthesis of cell wall do not
interfere with eukaryotic cell
• Due to the lack of cell wall in animal cells and differences in cell
wall in plant cells

Betalactams

Very safe
These drugs have very high therapeutic index

• Low toxicity with high effectiveness
– Antimicrobials of this class include
β lactam drugs • Vancomycin • Bacitracin


• Penicillins and cephalosporins are bactericidal.

• Penicillins are more effective against Gram+ bacteria.
This is because Gram + bacteria have penicillin binding
proteins (PBPs) on their walls.

This inactivity against Gram-negative rods was subsequently

found to result from:
(1) Inability to penetrate the Gram-negative cell wall;

(2) lack of available binding sites (penicillin-binding proteins);
(3) enzymatic inactivation in the periplasmic space

Intensive research led to the isolation of the active moiety, 6-

aminopenicillanic acid, in the penicillin molecule. This moiety,
which consists of :
thiazolidine ring (A) attached to a beta-lactam ring (B) that
carries a secondary amino group (R-NH-), is essential for
antibacterial activity

Alexander Fleming’s observation in 1928 that colonies of

staphylococci were lysed on a plate contaminated with a
Penicillium mold was the discovery that led to the
development of antibiotics. In 1940, Chain and Florey
and their associates were the first to produce sufficient
quantities of penicillin from cultures of Penicillium
notatum.
.
HUVEPHARMA B-ACT therapy
Basics of antimicrobial INTERMEDICAVET
Effective combination
These penicillins are combined with beta-lactamse

inhibitors to increase their range of antibacterial
activity.

Mode of Action
Beta-lactam antibiotics prevent the bacterial cell wall from forming by
interfering with the final stage of peptidoglycan synthesis. They inhibit
the activity of the transpeptidase and other peptidoglycan-active enzymes
called penicillin binding proteins (PBPs; transpeptidases,
carboxypeptidases), which catalyze cross-linkage of the glycopeptide
polymer units that form the cell wall.
The drugs exert a bactericidal action but cause lysis only of growing cells,
that is, cells that are undergoing active cell-wall synthesis.
.
.
Optimal antibacterial efficacy is time- and not
concentration-dependent and therefore requires that
serum concentrations exceed MIC of the pathogen for
essentially the entire dosing interval, so that these drugs
are best administered frequently or by continuous
infusion
.
Group of Extended-Spectrum Penicillins: Amoxicillin

Amoxicillin have the advantage of achieving higher tissue concentrations because of
better absorption from the intestine.
 These broad-spectrum drugs,, have considerably great activity against Gram-negative

bacteria such as E. coli, P. mirabilis, and Salmonella.

The basic pharmacokinetic properties of Amoxicillin
1- Amoxicillin are relatively stable in acid.

2- The systemic availability of amoxicillin (60–70%)
3- The absorption of amoxicillin is unaffected by feeding,
unlike ampicillin.

Activity against Anaerobes
Penicillins (penicillin G, amoxicillin, ampicillin, ticarcillin) are effective against most
anaerobes,
Metronidazole
Chloramphenicol
Clindamycin,
Some second- (cefoxitin) and third-generation cephalosporins (ceftizoxime)
. Macrolide (Tylosin) and tetracyclines have some activity against anaerobes but
they are rarely indicated as first line therapy for infections caused by anaerobes

Effect of B Lactam
The reportedly short half-lives of both amoxicillin

when administered to poultry species is a desirable
characteristic from the perspective of managing
withdrawal times in broiler flocks, where this can
be a factor limiting the options available for
treatment.
.
Effect of B Lactam
One potential factor that may limit the use of these

products is the reportedly poor stability of
amoxicillin in aqueous solution.
The only cephalosporin used in poultry production
is ceftiofur,

Effect of B Lactam
The only cephalosporin used in poultry production

is ceftiofur
It is commonly administered along with Marek’s

disease vaccine to day-old chicks either
subcutaneously or by in-ovo injection at
approximately 18 days of incubation
Aminopenicillin
* Group: Belongs to the group of extended spectrum beta-lactams
• MOA: Destroys the bacterial cell wall or prevents its formation

so it is a killer of bacteria
Basics ofBasics
of antimicrobial
Difference
Amoxy is Better than ampicillin in:
1- More effective than ampicillin on Gram negative bacteria

( it easily penetrate the Gram Negative Bacterial Cell Wall)
2- Higher systemic availability (twice)
3- Amoxycillin absorption is not affected by the feed
Basics ofBasics
of antimicrobial
Amoxyveto 50 S extra
Buffer Chelating agent

Traditional Amoxy
Glidant
Taste improver
Others
Manufacturing tech.
Basics ofBasics
of antimicrobial
Amoxy disadvantage
* Acidic (PKa = 2.7)
• Traditional Amoxycillin has the following disadv.:

1- Average solubility in fat
2- Found on trihydrate salt - non palatable
• Bad Stability in drinking water (6 hours)
• It has a moderate degree of solubility especially in pulsed dose
Basics ofBasics
of antimicrobial
Amoxy.
* Low binding with plasma protein (30 %)
* The rate of availability (F) mouth = 70-80%
* Circulate less during the portal circulation
• It is excreted mainly by the kidneys
Basics ofBasics
of antimicrobial
Amoxy
* Effect:
- Bacteria, especially E. coli - Salmonella - Pasteurella - -Hemophilus -
ORT- intestinal spirochetosis- staph and strept
- Used to treat (NE)
^ Has no effect on mycoplasma…… why ??
Basics ofBasics
of antimicrobial
Amoxy.
* Effect:
-
Masking effect :There is a synergism with Colistin ;
sterptomycin or neomycin
They Eliminates the protective effect of flora around
C. perfringens and facilitate the access of Amoxy for
treatment
Basics ofBasics
of antimicrobial
Amoxy.
* Dosage:
- Drinking water: 20 - 40 mg / kg / day / 5 days
A dose of 200-400 ppm (200 mg / L ) in drinking water is used
- Injection (IM / SC): 10 - 20 mg / kg / every 12 hours / 3-5 days
Basics ofBasics
of antimicrobial
Amoxy.
- Synergism with metronidazole - colistin - aminoglycoside - quinolone
^
Addition of Clavulanic acid (betelactamase inhibitor) to amoxicillin (1: 4) increases the
effective and effective effect of amoxicillin against bacteria which produces the
betelactamase enzyme such as staphylococcus; E. coli; Salmonella; Pasteurella and
Hemophius
-
Compatible with macrolide
Antagonistic with with sulfa-tetracycline-florfenicol
* Period of withdrawal:
- Meat: 3 - 7 days
- Eggs: 9 days (not used in layers *)
Basics ofBasics
of antimicrobial
Amoxy.
Amoxycillin Ampicillin
Absorption 75 % 50 %
Affected by feed Not affected Severely affected
Excretion Kidney Bile , little by kidney
Gut activity Less More
Enterohepatic circulation - +
Anti-Clostridium ++ +++
E coli & Salmonella +++ ++
Systemic High Low

Effect on bacteria Rapid bactericidal Slower
Basics ofBasics
of antimicrobial
Amoxy.
Cefotaxime Cefopyrazone
Absorption after inj. Very good
Enteric and systemic +++ +++
E.coli
Systemic High Low
Basics ofBasics
of antimicrobial
25 IU / kg for 2 days Penicillin G sodium =
avian spirochetosis
Acid sensitive Gram positive
- 1 mg = 1670 IU
25 IU / kg for 2 days Procaine penicillin

avian spirochetosis
Acid sensitive Benocaine penicillin
- .Long acting
Phenoxy methyl
penicillins = Penicillin
ACID STABLE 35 IU / kg for 2 days NE Oral active V
penicillin
"Ospen"

20 mg / kg 3-4 days Salmonella E.coli
NO INCOMPATIBILITIES
Orally NE Cefradin
10 mg / kg IM 2 days Salmonella E.coli

injection NE Cefadroxil
Antibetalacamase 2 mg / kg IM 2 days
Can not be mixed with injection Salmonella E.coli
streptomycin NE Ceftifur
Spectinomycin
Gentamycin
Kanamycin . 10 mg / kg IM 2 days Salmonella E.coli
injection NE cefotaxime
10 mg / kg IM 2 days Salmonella E.coli

injection NE Cefoperazone
Amoxy.
Cefopyrazone Cefotaxime
Absorption 75 % 50 %
Affected by feed Not affected Severely affected
E coli & Salmonella +++ ++
Systemic High Low

Effect on bacteria Rapid bactericidal Slower
Basics ofBasics
of antimicrobial
Damage to Cell wall (bacitracin )
Information No. 37 /5
.
Its effect is local, as it essentially not absorbed when administered
orally in poultry.
Bacitracin is a very effective antimicrobial for treatment of Gram-
positive enteric infections such as necrotic enteritis caused by
Clostridium perfringens.
Drinking water and feed additive formulations
BMD =1 gram / 3 liters /12 hrs / 4 days – only NE (Not others)
Damage to Cell membrane
Basics ofBasics
of antimicrobial
Damage to Cell Membrane Function

• Cytoplasmic membrane beneath cell wall controls flow of materials
into and out of cell; if damaged, contents leak out and results in cell
damage or death
• Outer (LPS) membrane of G- cell wall

• Polymyxins –effects phospholipids of G- cell & outer membrane
only
Basics ofBasics
of antimicrobial
Polypeptide :
Polymyxins,, bacitracin, and fosfomycin and glycopeptid
are peptide antibiotics with a variety of actions against bacteria.

. There is increasing use of these “last resort” drugs in veterinary
medicine as well as human medicine
Basics ofBasics
of antimicrobial
Polymyxin E (colistin) and polymyxin B are the only polymyxins used

clinically.
When first developed in the 1940s they were of great interest for their activity
against Pseudomonas aeruginosa. They were limited mainly to oral (colistin) or
topical (polymyxin B) use due to their systemic toxicity.
But more recent studies suggest that they are far less toxic
Basics ofBasics
of antimicrobial
1 mg of Colistin = 24000 IU
They are stable, highly water-soluble drugs
Basics ofBasics
of antimicrobial
Colistin
Basics ofBasics
of antimicrobial
Colistin
Belongs to the family polypeptide has been discovered in 1950, where it was extracted
from Fermentation Bacillus polymyxa var. colistinus is also known as polymyxin
*Polymyxins are cationic, surface-active agents that displace Mg2+ or Ca2+

To disrupt the structure of cell membrane
Unique action:Polymyxins disorganize the outer membrane of Gram-negative bacteria

by binding lipopolysaccharides (LPS, endotoxin) through direct interaction with the
anionic lipid A region. This action neutralizes the endotoxin capacity of LPS
Basics ofBasics
of antimicrobial
Colistin
he bactericidal activity of polymyxin B is concentration

dependent
• Uses sulfate -base salt (pKa = 10.4) - soluble in water
^ 1 mg of colistin sulfate = 24 thousand IU
* Resistance against it is slowly formed (uncommon)
* The rate of availability (F) mouth = 0 - 5% -
Basics ofBasics
of antimicrobial
Colistin
Absorption is very weak of the digestive tract So when given in drinking water,
it treats the intestinal infection, but when given Injectable (IM - SC) it treats the
systemic infection
^ Colistin absorption is related to the age of birds where it can be absorbed at
ages (less than a month) by up to 5%
* excreted through stool when given in drinking water and through the kidney
(slowly)At injection
Basics ofBasics
of antimicrobial
Colistin
Effect:
- Negative bacteria - E. coli - Salmonella – Pasteurella - Hemophilus
* Dosage:
- Drinking water: 75 - 100 thousand international units / kg / day / 3-5 days
- Injection (muscle: subcutaneous): 50 thousand international units / kg / for a period not
exceeding 3 days
^ High toxicity on the kidneys when administered by injection **
Basics ofBasics
of antimicrobial
Colistin
Is Colistin against Clostridium?

It it must be used in NE ?
Basics ofBasics
of antimicrobial
Colistin
Why resistance against against

colistin is very uncommon ?
Basics ofBasics
of antimicrobial
Colistin
Drug Interactions:
- synergistic with penicillins - macrolide - tetracycline - sulfa - quinolone
- Compatible with aminoglycoside
- Antagonistic with florfenicol - bivalent and trivalent salts
- Meat: 3 days (in drinking water) and 21 days (at the injection)
- Eggs: 0 days (in drinking water) and more than 8 days (injection)
Basics ofBasics
of antimicrobial
Inhibition of protein synthesis
Basics ofBasics
of antimicrobial
 Structure of prokaryotic ribosome acts as target for many

antimicrobials of this class
 Differences in prokaryotic and eukaryotic ribosomes
responsible for selective toxicity
 Drugs of this class include
30S: 1. Aminoglycosides 2. Tetracyclines
50S: 1. Macrolides 2. Chloramphenicol 3. Lincosamides
Basics ofBasics
of antimicrobial
Aminoglycoside
Aminoglycosides must penetrate bacteria to assert their effect.

Penetration can be enhanced by the presence of a drug that
interferes with cell wall synthesis, such as a beta-lactam
antibiotic.
Basics ofBasics
of antimicrobial
Aminoglycoside
Susceptible, aerobic Gram negative bacteria actively pump the

aminoglycoside into the cell. This is initiated by an oxygen-dependent
interaction between the antibiotic cations and the negatively charged ions
of the bacterial membrane lipopolysaccharides. This interaction displaces
divalent cations (Ca++, Mg++), which effects membrane permeability.
Basics ofBasics
of antimicrobial
Aminoglycoside, why it is cidal rather than static ?
- Induce an abnormal protein production rather than

inhibit the synthesis
- The abnormal protein form channel affecting
permeability additional uptake death
- Irreversible binding to ribosomal subunit
- Mature side of long chain rather than elongated side of
amino acid chain
Aminoglycoside
THE ONLY BACTERICIDAL PROTEIN SYNTHESIS INHIBITOR

Once inside the bacterial cell, aminoglycosides bind to the 30S ribosomal
sub-unit and cause a misreading of the genetic code, interrupting
normal bacterial protein synthesis.
This leads to changes in the cell membrane permeability, resulting in
additional antibiotic uptake, further cell disruption, and ultimately, cell
death
.
Basics ofBasics
of antimicrobial
Aminoglycoside
The bactericidal effect is through the formation of abnormal cell

membrane channels by misread proteins
Basics ofBasics
of antimicrobial
Aminoglycoside
Aminoglycosides Irreversibly binds to 30S ribosomal

subunit
• Causes distortion and malfunction of ribosome
• Blocks initiation translation
• Causes misreading of mRNA Not effective against anaerobes
HUVEPHARMA B-ACT therapy

Basics of antimicrobial INTERMEDICAVET
Aminoglycoside
Aminoglycosides are poorly absorbed from the normal gastrointestinal tract, but are
well absorbed after IM or SC injection.
Following parenteral administration, effective concentrations are obtained in synovial,

perilymph, pleural, peritoneal, and pericardial fluid
When given to animals with enteritis, oral absorption may be significantly

increased and result in tissue residues in food animals.
Basics ofBasics
of antimicrobial
Gentamicin
 the most widely used aminoglycoside, and it is used primarily as
a day-old subcutaneous injection or in ovo injection in chickens
or turkeys
A dose of 5 mg/kg body weight in broiler chickens has been
reported to be a suitable therapeutic dose when administered
either intravenously, intramuscularly or subcutaneously.
Aminoglycoside
Gentamicin
Subcutaneous administration was associated with the best absolute
bioavailability (100%), while oral administration had an absolute
bioavailability of zero
. Because gentamicin is a highly basic compound, it can damage cell-
associated Marek’s disease vaccine if used at too high a dose (greater than
0.2 mg/chick) or improperly mixed with the vaccine)

Aminoglycoside
Information
. No. 38/6
Neomycin
 commonly used to treat enteric infections, administered either in the
feed or water. Interestingly
despite poor absorption from the gastrointestinal tract there are reports
that administration of neomycin has resulted in clinical efficacy in the
treatment of colibacillosis in poultry, likely due to a local effect
Basics ofBasics
of antimicrobial
Aminoglycoside
Spectinomycin
A relatively safe antimicrobial in poultry that when administered
once orally, at doses of 50–100 mg/kg body weight, has limited
absorption from the gastrointestinal tract with absolute
bioavailability reported as 11.8% and 26.4%, respectively
Basics ofBasics
of antimicrobial
150 mg / kg E coli Salmonella
IM 2 days .Pasteurella Streptomycin
500mg / liter DW
UE Least toxicity
4 days
60-70 g / ton Rapid resistance
UE Propylaxis
Continuous
5 mg / kg E coli Salmonella
IM 2 days Pasteurella GENTA
10 mg / kg E coli Salmonella ‫مثل‬
IM 2 days Pasteurella KANAMYCIN
10 mg / kg E coli Salmonella ‫مثل‬
IM 2 days Pasteurella AMIKACIN
NEOMYCIN
10 -20 / liter DW
.Non-specific enteritis Most toxic
3 days
Least resistance
Aminoglycoside
• Not more than 5 days  severe effects on microflora
• Synergistic effect with aminopenicillin due inhibition of wall
 great uptake
• Aminoglycoside + linosamide + aminocyclitol
• Neomycin is very stable and can be used due to non specific
bacterial enteritis
• It is not recommended to use any of aminoglycoside with 3rd
generation cephalosporins
Aminocyclitol
• Separated from aminoglycoside due to
1- The CHO radicle is galactose not glucose
2- Bacteriostatic not bactericidal
3- Much less toxic than aminoglycoside

Aminoglycoside
• Apramycin:
• Low absorption
• 22-25 mg / Kg IM 2 days
• Orally: 50 mg 5-7 days in DW
• Side effect is diarrhea , and treated with addition of
liquid mineral

Spectinomycin

Spectinomycin
• Belongs to the family of aminocyclitol (which are similar chemically with
aminoglycoside)It has been extracted from Streptomyces spectabilis
• * Although it belongs to the family of aminoglycoside, it is given a bacteriostatic

effect to Except Pasteurella where it gives a bactericidal effect
• * Does not have ototoxic and nephrotoxic effect
• * Inhibits protein synthesis as a result of inhibition of 30 S of ribosome
(bacteriostatic)
• * Found on salt (sulfate - hydrochloride)
• basic (7.PKa = 8) – dissolved In water - stable
•
Spectinomycin
• The rate of availability (F) mouth
For dose of 50 mg / kg 11% absorption
with a dose of 100 mg / kg 26 % absorption 26%
• * The resistance is developed rapidly
• *eliminated by stool when given in drinking water and through the kidneys
When given injections
• * Effect:
• - Has a limited-term effect against Gram negative bacteria and some
positive bacteria And mycoplasma
• - Used for the treatment of E. coli - Salmonella - Pasteurella – Rimerella -
Mycoplasma

Spectinomycin
• Dosage:
• - Used 15 - 30 mg / kg / 12 hours / IM or SC for a period of 3 – 5
days
• - 100 - 125 mg / kg / day in drinking water for 3 - 5 days
• Mixing spectinomycin / lincomycin by 2: 1
• (40-50 mg / kg) spectinomycin and 20-25 mg / kg lincomycin) is
given a broad spectrum / Bactericidal effect against bacteria

Spectinomycin
• * Drug Interactions:
• - synergistic with lincosamide - macrolide
• - Compatible with colistin (addition)
• - Contradicts with penicillins - florfenicol - Quinolone - Tetracycline
•
• * Period of withdrawal:
• - Meat: 5 - 7 days (in drinking water) and 15 days (at the injection)
• - Eggs: 0 days (in drinking water) and more than 9 days (at the
injection

Aminoglycoside
• Spectinomycin
• Low absorption : 11-26 %
• 50 mg /Kg bwt orally
• 25-30 mg / Kg IM 2 days
• Side effect is diarrhea , and treated with addition of liquid mineral
• Very well known to be used with lincomycin to control CCRD

Streptomycin
Basics ofBasics
of antimicrobial
Streptomycin
The beginning of the family of aminoglycoside was discovered in 1944
where it was
Extract it from the actinomycete species of streptomyces erythreus
* Protein synthesis is inhibited by inhibition of 30 S of the ribosomal
subunits, so it is lethal
Bactericidal
It also affects the permeability of the bacterial cell wall
* Basic (PKa = 8.7) - dissolved in water (water-soluble)
* the aminoglycosides of least toxicity to kidneys
Basics ofBasics
of antimicrobial
Streptomycin
The percentage of availability (F) mouth = 1-2%
Intestinal absorption is very weak when given in drinking water it treats the
local intestinal infection, but when injected (SC-IM) it can treat the systemic
infection
In general, use of this family by injection is very useful in the treatment of

resistant bacteria to another
antibiotics (less toxic - less withdrawal period)
Basics ofBasics
of antimicrobial
Streptomycin
* The resistance is developed rapidly against streptomycin

* It is eliminated by stool when given in drinking water and 85 % through
kidneys in case of injection
* Has a toxic effect in the pigeons and ducks when given injecting more than
two days
Basics ofBasics
of antimicrobial
Streptomycin
Drug Interactions:
- Synergistic with with Penicillins - florfenicol * - Macrolide - Tetracycline
– spectinomycin
- Compatible with colistin - quinolone - clindamycin - amprolium
- Antagonistic with sulfa compounds as the chances of occurrence of renal
toxicity increase
- Meat: 4 days (in drinking water) and 30 days (at injection)
- Eggs: 0 days (in drinking water) and more than 9 days (at the injection)

Basics ofBasics
of antimicrobial
Tetracycline
Tetracyclins (Chlorotetracycline, Oxytetracycline) –

Reversibly bind 30S ribosomal subunit
Blocks attachment of tRNA to ribosome
Prevents continuation of protein synthesis
Effective against certain Gram + and Gram
Newer tetracyclines such as doxycycline (Semi-synthetic)
have longer half-life
Basics ofBasics
of antimicrobial
Tetracycline
MOA
The tetracyclines are pleiotropic drugs that classically are used as
protein synthesis inhibitors. Upon binding to the 16S RNA (rRNA)
and S7 protein of the 30S bacterial ribosome, they allosterically
inhibit the binding of aminoacylated transfer RNA (AA-tRNA) to
their site (A-site) on the ribosome.
Basics ofBasics
of antimicrobial
Tetracycline
MOA
Overall, they exert a bacteriostatic effect on susceptible bacterial
pathogens, with time dependent antibacterial activity
Basics ofBasics
of antimicrobial
Tetracycline
MOA
The tetracyclines possess an adjunct anti-inflammatory activity
that is valuable in controlling infectious disease.
They inactivate the matrix metalloproteinases by interacting with

the structural (not catalytic) Zn2+ and/or Ca2+ of these proteins,
and they scavenge the reactive oxygen species (antioxidant)
Basics ofBasics
of antimicrobial
Tetracycline
 The tetracyclines are the class of antibiotics with the highest use in
veterinary medicine
 They were the first discovered broad-spectrum antibiotics, acting against
Gram-positive and Gram-negative bacteria, mycoplasmas, some
mycobacteria, most pathogenic alpha-proteobacteria, and several
protozoan and filarial parasites.
 . This second generation of semisynthetic congeners (e.g., doxycycline)
has better pharmacokinetic and pharmacodynamic properties.

Tetracycline
The spread of tetracycline resistance and the

introduction of new large spectrum antibiotics limited
their medical use .
Basics ofBasics
of antimicrobial
Tetracycline
Their multivalent cation-chelating properties cause their deposition

in teeth and at sites of new bone formation. This feature has
toxicological consequences Poultry
Therefore the dosage of tetracyclines to laying hens on a high-
calcium diet should be increased.
Basics ofBasics
of antimicrobial
Oxytetracycline
• Belongs to the family tetracycline and has been derived from Streptomyces
rimosus
•
• MOA: Inhibits protein synthesis as a result of inhibition of 30 S of
ribosome (bacteriostatic)
• In therapeutic doses but at high doses has an effect on the 50 S part of

Ribosome
• * It is used on the form of hydrochloride salt - yellow powder – odorless –
stinging A little –
• alkaline (PKa = 9.1) – moderate fat solubility"
•
Oxytetracycline
• * Unstable (more stable than chlorotetracycline ) – chelating with
divalent cations
• - has an immune suppressive effect when injected
• * The percentage of availability (F) in the mouth = 50
• ^^ The use of acidifier-vitamin c improves its available ratio (F) for
tetracyclines
• Especially oxytetracycline and chlortetracycline which have a low
availability ratio compared to Doxycycline
Oxytetracycline
• Because of its low availability of oxytetracycline, it is required to be used at
high doses
• May be up to 100 mg / kg in severe cases
• * excreted through enterohepatic circulation in the bile (less than

• Chlorortracycline) and thus has high intestinal activity
• * Used in the field of veterinary medicine for more than half a century and
therefore there are many Resistant bacteria; Is still considered a good tool in
treatment
Tetracycline
• * Cross-resistance is common among family members but is less common with
doxycycline Minocycline
• The effect of tetracycline (especially oxytetracycline and chlortetracycline)

within the body are superior than in vitro, where tetracycline was found in diets
Poultry (200-400 ppm) infected by a pathogenic strain of E. coli-resistant
teracycline has limited pathogenicity of these bacteria by inhibition of Its GIT
attachment
• * It is eliminated by the bile and to some extent by the urine

• * Expired tetracyclines have a severe toxic effect on kidneys
Tetracycline
• Effect:
• - Has a wide-ranging effect against Gram negative and positive bacteria, either
aerobic or anaerobic
• ; Rickettsia; chlamydia; mycoplasma
• It is used for the treatment of Pasteurella – Hemophilus E. coli, Mycoplasma
has less effect against salmonella
• - Used for the treatment of gangrenous dermatitis (Gangrenous Dermatitis)
Oxytetracycline
• * Dosage:
• - 40 - 60 mg / kg / day for 3 - 5 days in drinking water
• For 5 - 8 days in feed
• - Inject dose 50 - 200 mg / kg for 3 - 5 days under the SC or IM
• ^ LOng acting products are injected with a 1 - 2 day interval between doses
• - Used in a dose of 400 - 800 ppm, whether in water or feed

oxyTetracycline
• - synergistic action with macrolides - aminoglycoside – colistin - metronidazole -
Lincosamide – Tiamulin - acidifier - bromohexine
• - Compatible with sulfonamide (additive )
• - Antagonistic with penicillins - Cephalosporin - Phenicol - Quinolone - Mineral
solutions
• Divalent and trivalent cations - vaccines - Vitamin B group
Tetracycline
• ^ Prolonged use causes the death of intestinal flora in addition to
deficiency For vitamin B and K
• - Meat: 3 - 7 days according to the dosage used (14 - 21 days at
the injection)
• - Eggs: 3 - 7 days according to the dosage used (12 days at
injection)
Doxycycline hyclate
Doxy
• Belongs to the family of tetracycline - semisynthetic - is derived from
chlorotracycline
• * Inhibits protein synthesis as a result of inhibition of the 30 S part of
the ribosome (bacteriostatic) in doses The therapeutic but at high doses
has an effect on the 50 S part of the ribosome
•
• * Doxycycline is alkaline (PKa = 9.5) - yellow powder – odourless -
A little tingling
* Used in salt (HCL), making it more stable and soluble in water
Doxy.
* The rate of availability (F) in the mouth = 60 - 85%
• Cross-resistance is less common with doxycycline

•
• * It is excreted by up to 75% by stool and the rest by urine

Doxy
• * Doxycycline is distinguished from other tetracyclines:
1. Less calcium chelation and more stable in water solutions

2 – More fat solubility (High Fat - Soluble) and therefore the spread of
tissues higher
3 – higher absorption oral dose
4- longer half - life (t1 / 2)
5- extensive plasma binding

Doxy
• Effect:
• - has a wide-ranging effect against Gram negative and positive
bacteria, whether air or anaerobic; Rickettsia;Chlamydia; Mycoplasma
- Used to treat Salmonella - E. coli – Pasteurella – Hemophilus and
Mycoplasma
• - Used for the treatment of (Gangrenous Dermatitis)

Doxy
• * Dosage:
• - It is used 15-20 mg / kg twice a day for 4 - 5 days in
drinking water and for the period 5-8 days in feed
• - It is used for the treatment and control of Mycoplasma

synoviae 100 - 200 mg / L

doxy
Drug Interactions:
• - Synergistic with macrolides - aminoglycoside - colistin -
metronidazole - lincosamide -tiamulin
• - Compatible with sulfonamide (additive)
• - antagonistic with penicillins – florfenicol - Quinolone –
divalent and trivalent cations
• - Meat: 5 - 6 days - Eggs: 28 days (not used in layers)
OTC 50 mg /kg bwt
3 days
Chelate divalent and trivalent
.DW
cation
15 mg / kg bwt Immune suppressive
.IM 2days
E. coli
CTC
Salmonella Chelate divalent and trivalent
Cholera 50 mg /kg bwt cation
coryza 3 days Immune suppressive
.DW Less absorptive
So higher gut activity
doxy
10-40 mg /kg bwt high absorption-
3 days Low chelation
.DW .Less immune suppressive
Type
DOXY CTC OTC
90-100 % 30-50 %
60-80 % F
low High
low Gut activity
High Moderate
High Systemic
Nil Moderate
Very strong chelation
In debate Moderate Immune
Very high
suppressive
Nil High Moderate Effect on flora
Very good Good
Good Efficacy
Precautions
In High dose of tetracycline ?

Precautions
• Depression of flora
• Clortracycline and oxytetracycline are used with copper sulphate to
increase efficiency and control the growth of fungi associated with their
use.
• Flourishing of flora
• After treatment with CTC and OTC it is preferable to add the yeast to the
feed and add a mixture of B K choline vitamins to the water to
compensate for the lack of vitamins resulting from the effect on intestinal
flora

Precautions
• Hard water
• Clortracycline and oxytetracycline are not recommended in hard water as
they affect their solubility and absorption.
• Chelation
- We should reduce as much as possible the addition of chlorortracycline
and oxytracycline to the feed as they affect the absorption of poly-valent
cations such as calcium, magnesium and iron, showing problems of bone
softness and weak egg shell.

doxy
Neomycin or colistin: When using CTC and OTC in the treatment, it is
preferable to use them with neomycin or colistin to increase the absorption
• The effectiveness of tetracyclines can be increased by either excluding the
calcium added to the mixture and replacing it with sodium sulfate with
13.6 kg per ton of feed. The latter excludes the dissolved calcium in the
intestine by forming calcium sulfate instead of calcium union with
oxytetracycline or by adding terephthalic acid acid at 3.6 kg / ton feed.
- Add acid terephthalic to increase the effectiveness of Clortratcellin to
four times and increase the effectiveness of oxytracycline to double.
Oxytetracycline is immunosuppressive, so it is recommended not to use it
before or after vaccines 24 hours.
Macrolides
Basics ofBasics
of antimicrobial
Macrolide
Basics ofBasics
of antimicrobial
Macrolide
MOA
Macrolides inhibit protein synthesis by reversibly binding to 50S subunits of
the ribosome. They inhibit the transpeptidation and translocation process,
causing premature detachment of incomplete polypeptide chains.
Basics ofBasics
of antimicrobial
Macrolides
Macrolids – Reversibly binds to 50S ribosome
• Prevents continuation of protein synthesis
Effective against variety of Gram + organisms and those responsible for atypical
pneumonia
Often drug of choice for patients allergic to penicillin
Macrolids include • Erythromycin, Spiramycin and Tylosin
– Resistance can occur via modification of RNA target
• Other mechanisms of resistance include production of enzyme that chemically modifies
drug as well as alterations that result in decreased uptake of drug
Basics ofBasics
of antimicrobial
Macrolide
Composed of factors
A B C D
Basics ofBasics
of antimicrobial
Macrolide
Anti-inflammatory and Prokinetic Activities of Macrolides

Macrolides have immunomodulatory effects
Recent studies suggest an effect of macrolide on adaptive immunity as well.
Basics ofBasics
of antimicrobial
Lincosamides, pleuromutilins, and streptogramins
are structurally distinct but share many common properties.
 They are basic compounds

 High lipid solubility
 Wide distribution in the body
 Capacity to penetrate cellular barriers. share overlapping
binding sites on the 50S subunit of the ribosome.
Mycoplasma
Mycoplasmas are often both hard to isolate and slow growing.

As a consequence, treatment of mycoplasmas infections is usually empirical rather than
based on in vitro susceptibility. Elimination from tissues is often slow
since most antibiotics have only a bacteriostatic effect against mycoplasma.
Despite excellent activity in vitro, treatment of established mycoplasma infections
in animals has sometimes been disappointing, perhaps because effective treatment
may require a 2- to 3-week rather than a shorter course.

Mycoplasma
It is difficult to ascertain susceptibility since in vitro testing of isolates is difficult, and is

usually not performed except by specialized laboratories. There are currently no MIC
testing control standards for veterinary mycoplasmas and breakpoints have not yet been
determined by the CLSI; as a result; MIC data cannot be defined as susceptible,
intermediate, or resistant. There is need to examine in vitro activity of animal-derived
mycoplasma more frequently than has been done in the past.

Tiamulin
Tiamulin, a semisynthetic macrolide available outside the United States for poultry,
has excellent efficacy against Mycoplasma spp. infections
It is important to note, however, that with the exception of lasalocid, tiamulin is

incompatible with the ionophore anticoccidials; monensin, salinomycin, narasin,
maduramicin, and semduramicin.
Administration of tiamulin with these ionophores results in clinical signs consistent

with ionophore toxicity, and seems to interfere with metabolism and excretion of these
compounds

Tylosin
Basics ofBasics
of antimicrobial
Tylosin
* The product of fermentation for Streptomyces fradiae and belongs to the macrolide
family
It is considered one of the best known antibiotics in the field for treatment of Mycoplasma
in birds
* Inhibits protein synthesis as a result of inhibition of 50 S of ribosome (bacteriostatic) In
therapeutic doses but at high doses has (Bactericidal ) effect
* Consisted with a core of Factor A with a small amount of 3 other molecules:
Desmycosin (factor B), Macrocin (factor C) and relomycin (factor D)
* Tylosin base (PKa = 7.1) - White powder - Dissolve in fat
Tylosin
Associated with organic or inorganic acids to form more soluble salts like
tartrate and Phosphates
^ tartrate salt is best absorbed when given in drinking water

Products prepared for injection (Intra muscle or subcutaneous) typically
contain 50% Propylene glycol and tend to precipitate when mixed with
other drugs (causes Temporary irritation and pain at the injection site)
^

Tylosin
*Phosphate salt has a high stability so it is used in the Premix but The
dosage should be increased
* The percentage of availability (F) in the mouth = 40 - 70% (variable)
Like erythromycin, tylosin has good circulation in the tissues (liver-lung-

trachea - air sacs - ovaries - muscles - kidneys) up to 3 – 5 Times more
than its concentration in plasma
* It is also excreted by the kidneys and in large amounts in bile reach to
cecum
* Has PAE up to 6 hours
Tylosin
* Effect:
- Chicken Mycoplasma has a high sensitivity to Factor A
- Tylosin is generally effective against Gram positive bacteria; and special effect against
Mycoplasma gallisepticum and some Gram negative bacteria
^ Mycoplasma gallisptecum; synoviae, and meleagridis
Also effective against streptococcus, clostridia, hemophilus , Pasteurella,Chlamydia,
Rickettsia also has a inhibitory effect on Eiemria tenella

Tylosin
The bacteria that resist tylosin also resist erythromycin
- The resistance of Mycoplasma and Staphylococcus against tylosin is very

small
Cross-resistance arises in a variable manner with erythromycin , spiramycin ;
lino-spectinomycin
Dosage:
- 80 - 100 mg / kg / day for 3-5 days in drinking water or 5-7 days in feed
- For the treatment of mycoplasma
Tylosin
* Drug Interactions:
- synergistic with tetracycline - sulfonamide - aminoglycoside - colistin -
spectinomycin – Apramycin - Fluorquinolone
- compatible slightly with aminopenicillin (amoxicillin - ampicillin)
- antagonistic with penicillins - lincosamide - phenicol - other macrolides
- Meat: 1 - 3 days
- Eggs: 3 - 5 days

Staph
20 mg / kg bwt /12 hrs/ 4 days Strept
No injection Mycoplasma Erythromycin
Low effect on clostridium
.
Tylosin
50-100 mg / kg bwt /12 hrs/ 4 days
No injection .Tartrate –Phosphate-thiocyanate
.Compatible with doxy Mycoplasma
Staph strept
Good on Clostridium
25 mg / kg bwt / 12 hrs / 4 days Tylvalosin
No injection Acetyl isovaleryl tylosin tartarate
Compatible with doxy
.
Mycoplasma
64000-128000 IU / kg /bwt /12 hr
.Injectable
Staph strept Spiramycin
Low on Clostridium
9 M IU / kg /bwt /12 hr
Injectable Josamycin
. Mycoplasma
50 mg / kg bwt /12 hrs/ 4 days Staph strept
.No injection ..Good on Clostridium Kitassamycin
20 mg / kg bwt /12 hrs/ 4 days
No injection
Tilmicosin
Lincomycin
lincomycin
• Belongs to the family of lincosamide and has been extracted from
Streptomyces lincolnensis
• It was discovered in 1950 and was introduced for veterinary use in 1967
•
• * Inhibits protein synthesis as a result of inhibition of 50 S of ribosome
(bacteriostatic)
• * Lincomycin weak base (6.PKa = 7) - Crystal white powder with odorless
soluble in fat - stable even when reacting with light and Air
• * Must be kept at a temperature not exceeding 40 degrees Celsius (15 - 30
degrees)
• * Has a cross-resistance with macrolide - clindamycin as well as
streptogramin
lincomycin
• * Its absorption is affected by the presence of feed in the intestines
• * The percentage of availability (F) by mouth = 40 - 50%
• It distributed within the cells and is concentrated in the tissues up to 8 times
its concentration in plasma blood
• * Activates the cells of the alveolar sacs in the lungs (alveolar macrophages)
• * Has a good PAE allowing to extend the interval between doses to 10 - 12
hours
• * It is excreted by bile most often (it is re-absorbed from the duodenum
through enterohepatic circulation) and sometimes by kidney

lincomycin
• It is also excreted through the skin so it is used to treat
gangrenous dermatitis (GD)
• * Effect:
• - has a similar effect to the action of erythromycin and also to
penicillin G and phenoxy Methyl Penicillin (Penicillin V) as it has a
high activity against positive and anaerobic bacteria
• - Has little effect (or no effect) against the majority of negative
bacteria

lincomycin
• Dosage:
• - 2 - 4 mg / kg feed is used as a growth promoter
• -for necrotic enteritis

• A therapeutic dose A dose of 10 - 50 mg / kg in drinking water
• Prophylactic :With a dose of 2 - 8 parts per million (in feed as premix)
and in a dose 15 - 20 mg / liter water / day / for 7 days

lincomycin
• - synergistic with spectinomycin ** - tetracycline - aminoglycoside

• - antagonistic with penicillins - florfenicol - quinolone - Tiamuline -
macrolide – amprolium- acidifier
• - Meat: 3 - 7 days
• - Eggs: 5 days (not used in layers)

Affected by feed Mycoplasma
15-22 mg / kg
Mixed with Clostridium
bwt / 3-4 days Lincomycin
speectinomycin Staph
.
.against CCRD .
Mycoplasma
Clostridium
Not Affected by 15-22 mg / kg Staph strept
feed bwt / 3-4 days Better on clostridium Clindamycin
especially in systemic
condition and in
cholangiohepatitis
Antibiotic abuse in Veterinary
medicine

Antibiotic abuse in Veterinary medicine
Mistake No 1
1-Mixing of cephalosporins such as, cefotaxim,

cephopirazone or ceftiofur with gentamicin sulfate,
streptomycin sulphate, sapetinomycin sulphate and
lincomycin hydrochloride due to chemical damage to
all blended materials

Mistake No 1
because the second or third generation of cephalosporins carried on

with sodium salt while others are Salt of sulphate or hydrochloric
acid
Sodium known as the most powerful metal , sulfate or
hydrochloride. Non-metals.
So the result of mixing strong metals such as sodium with strong
such as sulfate or hydrochloride just to destroy each other
chemically.
Mistake No 2
Use of sulfadamidine in the treatment of coccidia birds
because sulfadimidine is highly absorbable up to 90% from the

duodenum, while most of the types of dangerous coccidia occur
after post-duodenal, that the sulfadamidine disappear
sulfaquinoxaline or sulfaclozine OR sulfaguanidien are should be

used
. Basics ofBasics of antimicrobial
Mistake No 3
The use of amoxicillin along with sulfonamide
the binding of amoxy with plasma protein in the blood is higher

than that of sulfa compounds in blood proteins. This means the
release of a large number of sulfa compounds in the blood, which
leads to the destruction of kidney tissues. That if we have to treat
necrotic enteritis with coccidiosis, we can use ampicillin with
sulfaqininoxaline or sulfaclozine safely.
Mistake No 5
Use of spectinomycin alone for the treatment of Chronic

Respiratory Syndrome (CCRD)
where there is an immunosuppression due to concurrent infection
with mycoplasma, coliform bacteria and spectinomycin.
Bacteriostatic inhibitor, which depends on the immune condition
Immune dependent, which cannot be used alone during
immunosuppression.
spectinomycin with lincomycin as they give together a bactericidal
combination which is Immune independent.
Mistake No 6
Inject the birds with antibiotics once and not to

repeat the injection the next day immediately
because the conc. of antibiotics used will not
reach the MIC causing the occurrence of
microbial resistance used antibiotics.

Mistake No 7
antibiotics Injection the birds followed by

drinking water administration

Mistake No 8
Doxycycline when mixed in very high doses with

tylosin
in this case doxycycline works on 50 s of ribosome

rather than on 30 s of ribosome, which leads to the
occurrence of competitive inhibition between them.
Folic acid synthesis inhibition
Mistake No 9
Mixing doxycycline with doses much lower than doses

with tylosin
because in this case the mixture will not be converted
into a bactericidal of Bactericidal. The mixture will
continue to act as Bacteriostatic bacteria, which
depends on the immune condition.
Mistake No 10
Use of immunosuppressant antibiotics

immediately before or after immunization
Mainly oxytetracycline, chlorotracycline and

sulfa compounds

Mistake No 11
Use tetracyclines or OTC +K citrate or Na

citrate or NaHCO3,
reducing the absorption of tetracyclines

.

Mistake No 12
the use of tetracyclines group "Bc +

compound, which caused the gradual
inhibition of tetracyclines

Mistake No 13
The use of quinolones, especially norfloxacin and

difaloxacin in doses higher than the doses of
quinolone will act as Bacteriostatic and not
Bactericidal bacteria.

Mistake No 12
Use of quinolones + with K citrate or Na citrate or

NaHCO3,
because of the contrast between them leads to the

precipitation of quinolones in the kidneys with the
formation of crystals
Information No. 1
Use of quinolones +sulfa and trimethoprim

because of the antagonism
Use of quinolones + bacitracin, which reduces

the absorption of quinolones.

Mistake No
Use of macrolides +lincosamides + pluromothelins

with each other or with phenicols because this is
because of:
competitive inhibition and the liver burden

Thank you

Antimicrobial Final

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Antimicrobials

Aim of medication Prevention of some important poultry disease:

Prophylactic medication is usually used in the poultry practice

2-In feed use of different anticoccidial drugs e.g. ionophores, clopidol

Basics of antimicrobial therapy

5-In feed use of different anti-mycotoxins drugs

Basics of antimicrobial therapy

From ancient to the future

Basics of antimicrobial therapy

Time – types –Location-

R espiratory flora: trachea 10 000 times less than 1 gram of GIT(102-105)

1- Immune suppression (Under stress)

Basics of antimicrobial therapy

 Antibacterials: completely synthetic chemical substances: many

Basics of antimicrobial therapy

The success of antimicrobial therapy depends upon many interacting factors,

Basics ofBasics of antimicrobial

Basics ofBasics of antimicrobial

The activity of an antimicrobial agent against a particular

Basics of antimicrobial therapy

Basics ofBasics of antimicrobial

1- The drug can reach the site of infection

This frequently leaves the poultry veterinarian with an antimicrobial

The primary criterion for measuring success of treatment under

1- Reduction of morbidity and mortality.

Basics ofBasics of antimicrobial

Basics ofBasics of antimicrobial

 Antimicrobial therapy involves a calculated risk that

Basics ofBasics of antimicrobial

 The aim of antimicrobial therapy is to assist the

 In doing so the pathogen’s ability to:

 The overall result is elimination of the infection with

Basics ofBasics of antimicrobial

 Systemic availability is influenced by the stability of an

Basics ofBasics of antimicrobial

 Presystemic metabolism, referred to as the first-pass effect, can

 The first-pass effect decreases the systemic availability of drugs that

 Presystemic metabolism activates p. Metabolic conversion (N-

 Examples of lipophilic antimicrobial agents include

Basics ofBasics of antimicrobial

80-70 DOXY 5 AMINOGLYCOSIDE

 While absorption from parenteral sites is mainly controlled by

Basics of antimicrobial therapy

 Selective binding to a tissue component

e.g., Aminoglycosides to phospholipid-rich tissues of the inner ear and

 Some of these drugs (Erythromycin, clindamycin, doxycycline) bind

Of the lipophilic antimicrobials, only certain individual drugs penetrate

 In the presence of meningitis, most intravenously administered third

Basics ofBasics of antimicrobial

Gut absorbed Antibiotics

Basics ofBasics of antimicrobial

Gut non absorbed Antibiotics

Basics ofBasics of antimicrobial

Basics ofBasics of antimicrobial

Amoxycillin (Not ampicillin)

Basics ofBasics of antimicrobial

Bile (enterohepatic circulation)

Basics ofBasics of antimicrobial

Basics ofBasics of antimicrobial

Comparison between two types of data:

1- Sensitive: site conc. > MIC

Basics ofBasics of antimicrobial

whereas broad-spectrum drugs inhibit both Gram-positive and Gram-