Antibiotics

Antibiotics
Classification of Antimicrobials

ANTIMICRO-
BIALS

ANTIVIRAL
Agents
 Antibiotics:

Definition:
They are complex organic chemicals pro-
duced by living organisms as
MOULDS,FUNGI or BACTERIA during their
growth (METABOLITES) and are capable to
antagonise other microorganisms.
 Sources of Antibiotics
( Metabolic extracts from certain Moulds and Bacteria) antagonise bacterial
cells other than animal cells
Penicillum Notatum (MOLDS)

1928 Discovery of Penicillin by

Alexander Fleming
Preparation of Antibiotics from Natural
source
 Assay of Antibiotics
Sensitivity Test and Potency
Assay of Antibiotics
1.Disc or Cup Sensitivity Tests (Qualitative)

Most of biological tests depend on the use of an agar-based medium

seeded with selected strain of Standard sensitive bacteria e. B.Subtlis.
Standard Bacteria and unknown dilutions of antibiotics are placed in
Cups or wells in the agar and the plates are incubated at 37 C. Antibi-
otic diffuses from cups or wells to surroundings, so producing a zone
in which bacterial growth occurs.
The size of zone of inhibition is measured and propotional
 1.Biological Assay Methods

Zone of Inhibition of
Standard

zone of inhibition of
Unknown
 2.Serial Dilution Methods (Quantitative)

2 Tube serial dilution

Method for Antibiotic assay MIC or
MBC
 Definition

Minimum Inhibitory Concentration (MIC):

Lowest concentration which capable to inhibit the growth and multi-
plication of Bacteria ( BECTERISTATIC).

Minimum Bactericidal Concentration(MBC):

Lowest concentration which is capable to kill sensitive Bacteria
(Bactericidal Effects)
 2. Physico-Chemical Assay of Antibiotics

Techniques use for measuring the antibiotic concentration such as Spectropho-

tometry, Spectrofluorimetry, HIGH PERFORMANCE LEQUID CHROMATOGRAPHY
(HPLC) as Sofusticated.
Less sensitive than biological methods.
Used Mainly for detection of Antibiotic residues in food of animal origin as well
as drug evaluation and Pharmacokinetic studies
Safety Test:
Antibiotics must be prepared a pure and sterilized form after manufacturing
and Standardization and be free from any toxic materials
(pyrogen free)
Stability:

 Antibiotics become unstable in high moisture ,High

temperature( more than 25C) and direct light( Tetracyclines).

THEY ARE INFLUENCED BY: pH, Oxidizing agents, Heavy

metals( Iron, copper, magnesium, Mercury etc….), Minerals as cal-
cium and enzymes
Classification of Antibiotics
 Antibiotic Spectrum.1
The field of Abtibacterial Activity of Antibiotics

Narrow Spectrum Antibiotics .1 Broad Spectrum Antibiotics .2

The Antibacterial activity is restricted to They will affect a wide range of G+ve and G-ve,
:limited No. of Bacteria Mycoplasma Spp and even some protozoa.
e.g.Tetracyclines( G+ve,G-
e.g. Penicillin –G on Gram Positive bac-- ve,Mycoplasmas&Anaplasma.
teria as Staph.aureus, Streptococci, Florphenicol (G+ve & G-ve)
.Corynbacterium Spp Amoxycillin and Ampicilln (G+ve and –ve)
e.g Srteptomycin on G-ve- Cephalosporins( G+ve and G-ve)
e.g Tylosin against G+ve and My- Third Generation of Quinolones ( G+ve and G-ve
.coplasma Spp and Mycoplasmas

e.g Colistin against G-ve bacteria -

 Antimicrobial agents grouped accord-. 2
ing to anti-bacterial action

Bactericidal Bacteriostatic

Penicillins Tetracyclines
Cephalosporins Chloramphenicol
Amino glycosides Florphenicol
Bacitracin Marcolides
Polymyxin B and E(colistin) Lincomycin
Trimethoprim / Sulphonamide Spectinomycin
Quinolones Sulphonamides
Trimethoprim
 Antibiotics and Other Antibacterials.3
1. Penicillins 4.Tetracyclines 7. Polypeptides
1.Narrow spectrum
-Tetracycline. Colistin.
e.g. Penicillin-G
-Oxytetracycline. Polymyxin B
2. Semisyntectic
-Doxycycline.
-B-Litanies resistance
-Cloxacillin
-Dicloxaciln 5.Chloromphnicol 8. Aminocyclitol
3. Broad Spectrum
-Ampicillin .Florphenicol- Lincomycin.
-Amoxycillin. Apramycin.
6. Macrolides
2. Clephalosporins
9. Spectins
-Josamycin.
3. Aminoglycosides -Tylosin.
Spectinomycin.
-Spiramycin.
-Streptomycin. -Erthromycin.
-Neomycin. -Taimulin.
-Gentamycin Telmocosin
-Kanamycin. azthromycin
Synthetic Antibacterials
• Sulphonamides • Quinolones
- Sulphadimidine. - Nalidixic acid.
- Sulphadiazine. - Oxolinic acid.
- Sulphaquinoxaline. - Flumequine
- Sulphadimethoxine. - Enrofloxacin
- Silphamethoxypyridazine. - Danofloxacin
- Pefloxacin
• Trimethoprim • Furan derivatives
• TMP+S (1:5) - Furazoldone.
- Nitrofuazone.
- Furaltidone.

22
Bacterial Cell
Antibiotic Mechanism of Action
1. Antibacterial or Antibiotics inhibit Nucleic acid Synthesis
The replication of nucleic acid is inhibited by

Indiect or Metabolic effect

Direct effect ON RNA ON DNA
• Sulphonamides and
• Rifamycin specifically Trimethoprim decrease the
imhibits the enzymes synthesis of nucleic acid
concerned with Replica- • Quinolones e. g En-
rofloxacin ,Danofloxacin in-
tion of RNA (transcrip-
terfere with the replication
tion) of DNA by Inhibiting DNA
GYRASE enzyme responsible
for DNA REPLICATION
 Chemical Structure of sulphonamides

NH2 COOH NH2 SO2-NH2

Para-aminobenzoic acid Para-amino-benzene

similarity )PAPA(
sulphonamide
)sulphanilamide(
Nucleus is essentail for
THE ANTIBACTERIAL
ACTIVITY
Sulphonamides: These are derivatives of sulphonamide radical
(para amino benzene sulphonamide(sulphnilamide) to which
other radicals are attached(Sulphonamides or sulpha drugs)
They have the same structure of para amino benzoic acid(PABA)
.needs for bacterial growth

PABA FOLIC ACID

S

DIHYDROFOLATE
T
dihydrofolate reductase

TETRAHYDROFOLATE
Thymine Thymidine nuclotide
Oxyribose or dioxyribose RNA or DNA +
 Aminoglycosides Antibiotics: streptomycin, Neomycin,Gentamicin and
Kanamycin etc…
 Tetracyclines: Oxytetracycline, Doxycyline etc..
 Macrolide- Antibiotics: Tylosin,Erythromycin,
spiramycin,Azthromycin,etc…
 Lincosamide(lincomycin) and Spectinomycin.
Mechanism:
They can interfere with normal development of protein synthesis and
combination necessary for bacterial growth:
The process of linking together of Amino acids(condensation) or cyclic
combination attachment of Amino acids + Ribosomal Messengers( 30-
subunits or 50-sununits) are interrupted by Antibiotics and therefore
the protein of bacterial cell is not formed and the growth is stopped .
NORMAL BACTERIA

l wall
ce l
al
a c te ri
B
tRNA binds to the mRNA
ribosome complex
mRNA
30S

Ribosome tRNA

Elongation of the
peptide chain
Cyto- = Protein synthesis
plasma
 PHARMACODYNAMICS

ce ll
c t e ria l
Ba Binds to receptors
Tetracyclines wal
l
on the 30 S
Aminoglucosides 30S
mRNA

Nano particles diffusion

Ribosome tRNA
Active
carrier-medi-
ated INHIBITING BACTE-
transport RIAL PROTEIN SYN-
Cyto- THESIS
plasma
 PHARMACODYNAMICS
Mechanism of action

ce ll
c t e ria l
Ba Binds to receptors
l
wal on the 50 S
Macrolides and Flourphenicol mRNA
50S

Ribosome tRNA
Active
carrier-medi-
ated INHIBITING BACTE-
transport RIAL PROTEIN SYN-
Cyto- THESIS
plasma
 Linezolid

Daptomycin

Linezolid
 Antibiotics inhibit the cell wall formation e. g. .3
Penicillins and Cephalosorines
Peptidogylcan sheets are formed from Acetylmu-
ramic acid +acetylglucosamide and fixed by
Glycine
 Disruption of cell membrane function .4
e.gPoypeptides(
Surface-active Polymyxin B & Colistin)
polymixins
leads to escape of )detergent dissolving the cell membrane =(
cytoplasmic contents and bacterilysis
 Neutralizes endotoxins of several Gram- negative bacteria

O rg an igram titel

FAS T

In h ibits ox id a tiv e m e ta bo lism

D e s tro ys th e p erm e ab ility o f the b ac te ria l c yto p la sm ic m e m b ra ne

 MODE OF ACTION
:COLISTIN
binds to the bacterial cytoplasmic membrane 
reacts with phospholipids 
penetrates into cell membranes 
 disrupts the structure of the membranes

Bacterilysis !!!  Bacteria are killed

 -Entero
Toxins
HLT
HST
Cholera
like

E.Coli
Under
..Elect
Microscope

.E.coli
colonies
 no effect
Side effect
Toxicity
- Potentiates
- Spectrum
- Mechanism Broaden the spectrum
- Decrease Changes static to cidal
Toxicity effect
Minimizing resistance
Possible Interactions with Antibiotics
Objectives of Antibiotic combination
 1.They are widely used in Veterinary and human Medicine,
 2. To broaden the spectrum of activity against mixed infections e.g
Penicillin-G + Streptomycin , Colistin + Tylosin , Neomycin +
cloxacillin
3.To reduce antibiotic the toxicity of single administration required
in large dose.
 4. to subside the induction of drug resistance by bacteria ( Amoxy-
cillin + clavulanic acid “Agumentin”.
 5. to achieve drug addition e.g. Colistin + Amoxicillin , Sul-
phadimidine + sulphadiazine .
To achieve drug synergism e.g Sulpha + Trimethoprim
Rules regarding Antibiotic combination
are as follows:
Possible Therapeutic Combination Between An-
timicrobials
• Addition ; (+) (1+1=2)
- Potentiates
* spectrum
* mechanism
* decrease toxicity
Examples;
• Sulpha + sulpha or tetracycline
• Colistin + amoxycillin (cidal + cidal)
• Lincomycin + spectinomycin (static + static)
• Erythromycine + colistin
• Tylosin + colistin
• Doxycycline + colistin
• Lincomycin + colistin
• Amoxycillin + clavulinic acid

44
 Synergism (+) (1+1 = 4 or 8
 Broaden the spectrum
 Changes static to cidal effect
 Minimizing resistance
 Examples;
 - Sulpha + trimethoprim
 -Erythromycine + trimethoprim
 - Penicillin G + streptomycin
 - Josamycin + trimethoprim
 - Oxytetracycline + neomycin
 - Gentamycin + carbencillin
 - Amoxycillin + kitasamycin
 Antagonism
of Antibacterial combination( Types):
1.Inhibition of bactericidal activity by Bacteristatic agents e.g.
Penicillins # Sulpha drugs,Tetracyclines,macrolide-antibiotics
and Florphenicol.
2. Competition for drug binding sited e.g. Macrolides # chlo-
ramphenicol( 50-s ribosomal Messenger).
3.Inhibition of cell permeability mechanism. e.g. Chloram-
phenicol and spectinomycin # Aminoglycosides.
Chelating agent such as Calcium and Magnesium antagonise
the absorption of tetracyclines
Antagonism ; (-)
Examples
 Tetracycline * Chloramphenicol
Penicillins , Erythromycine
 Magnesium + Calcium with Tetracyclines
 Pencillins * spectinomycin
Sulpha or trimethoprim
 Gentamycin * sulpha
 Tiamulin * Monensin {ionophores} … Toxicity
 ++ chlorine * inactivates fluroquinolones
 Rusted or galvanized containers * inactivate neomycin and Furans *
Quinolones gentamicin, apramicin
 Chelation of Calcium with tetracycline leads to minimizing their in-
testinal absorption
 Bacterial Resistance
Is the ability of bacteria to resist the antibacterial activity of An-
tibiotics and other Antibacterial agents
 Natural or constitutive Resistance.1
 Certain bacteria are naturally resist some antibiotics as they lack the
cellular mechanism required for Antibiotic action e.g the resistance of
Gram negative bacteria (E.coli, Salmonella Spp, etc…)to Penicillin-G as
Penicillin-G is not able to penetrate the highly complicated cell wall of
Gram-ve bacteria and Stretomycin can not penetrate the cell wall of
Gram +ve bacteria.

 Antibiotic-Enzymatic inactivation: Enzymatic degradation of Antibi-

otics by naturally produced Bacterial Enzymes as Staph .aureus pro-
duce B-lactamases( Penicillinase or Cephalosprinase “ B-Lactam An-
tibiotics” . Acetylase and phosphorylase inactivate the Aminoglyco-
side Antibiotics
 Acquired or mutant resistance .2

Some bacteria which are originally susceptible

to Antibiotics become after excessive use in
sub-therapeutic doses or for long tem become
: resistant due to the following mechanisms
 Antibiotic Resistance
Four mechanisms of Aquired resistance
 1)Blocks antibiotics (blue spheres) because the bacterial cell mem-
brane is now impermeable to the drug e.g Tetracyclines
 2)Target modification: alters the proteins inhibited by the antibiotic,
so the drug cannot bind properly with 30-s sub unites of Ribosomal
messenger (aminoglycosides) and or 50-S subunits of Ribosomal mes-
senger ( Tylosin)
 3)Antibiotic modification produces an enzyme that inactivates the an-
tibiotic. As beta-lactamses and others
 4 )Efflux employs genes coding for enzymes that actively pump the
antibiotic out of the cell e.g. tetracyclines
 5.some Microorganisms develop and altered metabolic pathway e.g
Sulphonamides
 Antibiotic Resistance

2
1

4
3
3.Transmissible Resisitance
3. Transmissible Resistance
 Antibiotic resistance can be acquired in two basic ways. In vertical trans-
mission, a bacterium accumulates errors or mutations in its genome during
replication; some of those changes (red) give the ability to resist antibiotics
and are passed on to subsequent generations. In horizontal transmission,
resistant genes are swapped from one microbe to another.
 This can occur via three mechanisms:
 Transformation, when bacteria scavenge resistance genes from dead bac-
terial cells and integrate them into their own genomes( Genotype of naked
DNA transferred from bacteria to other by Transposons ( From Plasmid to
plasmid or from plasmid to chromosome and vice versa
 Transduction, when resistance genes are transferred by bacteriophages
(viruses that infect bacteria), Plasmid DNA is incorporated by bacterial cell
id transferred to another bacterium e.g. transfer of beta-lactamase gene
from resistant Staph .Spp to Susceptible Staph.aureus
 conjugation, when genes are transferred between bacterial cells through
tubes called pilli between E.coli and Salmonella Spp and vice versa
conjuga-
tion
 Importance of Transmissible Resistance
( therapeutic failure due to transmissible resistance)

 Transmission can be occured between species as well

as species from non pathogenic strains of E.coli to Sal-
monella spp.
Transmission of single plasmid may carry resistance to a
wide variety of unrelated antibiotics and also transmit the
virulence determinants such as the ability to produce tox-
ins.
Certain individuals may acquire a population of Bacteria
which would resist treatment through the host has not re-
ceived antibiotic treatment
Discovery of Penicillin by Alexander Flem-
ing 1928
Penicillins
 Penicillin-G
A narrow spectrum antibiotic acting on gram +ve bacteria.
Manufactured from Mould” Penicillum notatum” in a powdered for
unitage of Penicillin-G ( 1 Unit = 0.6 ug)
Chemistry

unstable Stable

site of action
of Amidase

R- 6-amino penicillionic site of action of B-lactamase Penicillionic acid

1928
 First pro-
duction of
Penicillin
Sodium and
used in WW
II
 ..… Penicllins
Other Simple peniciilins:
Penicliin K : Less effective
Penicillin V : PHENOXYMETHYL PENICIIIN ( stable
against gastric acidity and can be given orall)
Penicillin O : Has less allergic effect.
Penicillins : Are unstable and insoluble in water but solu-
ble in salting form (with Na+ and K+, procaine and
Stearate.
Stability of penicillin –G
:Is affected by

Others .5
Penicillins are af-
fected by Heavy
metals as
copper,Mecury,
Iron, zinc
:Pharmacokinetics of Penicillin-G( Benzyl Penicillin)
Absorption:
-- Inorganic salts of Benzyl Penicillin (Na+&K+) is absorbed only by I.M .
and when is given orally it is destroyed in stomach dur to gastric acidity.
--- It can be given I.V. or S/c routes
-- It is rapidly absorbed and rapidly excreted
Phenoxy Methyl Penicillin resists the gastric acidity and can be given orally
 Blood level : Bacteristatic con. 0.02 to 0.03 ug/ml
Bactericidal con. Over 0.5 ug/ml

 Barriers :
It is poorly diffused to cerebrospinal fliud, Placenta, intestine and
serous membrane ,
 Milk Barrier:
Benzyl penicillin is poorly diffused into milk, but when is given via
i.v. route it can rech the mammary cell. So it used locally in cases
of mastitis due to G+ve bacteria by Intrammary route.
 Excretion:
Following i.m. or i.v. penicillin –G is rapidly excreted via kidneys in
urine( 50 – 80%) within few hours
Antibacterial Spectrum:
It has a bactericidal action. It is a narrow spectrum, acts against Gram
+ve ( ( Staphylococcus Spp. Steptococcal Spp. Corynebacterial Spp.
Listeria Spp. And Closteridia and Paseurella Spp.
Resistance:
1. Natural resistance , can not act against G-ve bacteria
2. Enzymatic degradation due to B-Lactamases produced by
Staph.aureous
3. Transduction of R-Plasmides for the production of B-Lactamases
from Staph.aureous from Staph. to Staph.
Mechanism of Action: penicillin-G interferes will cell wall forma-
tion of immature cell during multiplication ,lead to osmotics destruc-
tion of cells (Bacterilysis).
 Dosage: Penicillin-G Sodium ( 15 – 20000 IU/kg) every 6 – 8
hrs
Procaine Penicillin ( 25000 IU/kg i.m. every 24 hrs
Phenoxy methyl penicillins 8 mg/kg Orally

Toxicity:
Little in Veterinary Practice from Benzyl Peni-
cillin, Allergic reaction may occure in small
animals and can treated with Anti-allergic
drugs .
Mechanism of action of penicillins (in-
hibits cell wall formation)
2.Semi-synthetic Penicillins
New Penicillins
Comparative features of Various Penicillins

Name Oral absorp- -B Antibacterial

tion Lactamase Spectrum
resisitance
PenicillinG Poor No Narrow
Penicillin V Good Gram +ve
Phenoxymethyl Good only
penicillin
Injectable

Methicillin Poor Yes narrow

Oxacillin Good
Cloxacillin Good
Naficillin vairiabel

Ampicillin Good
Amoxycillin Excellent No Wide
Carbencillin poor
d
 These types of Penicillin can resist the Betalactamese enzymes pro-
duced by certain Bacteria(Staph.Aureus,E.,Coli, Samonell SPP and
Klebsiella Spp. Attack ing B-lactum ring of penicllins.

 Cloxacillin and Oxacillin.:

 They are stable against penicillinase or B-Lacatamase enzymes
 Of only narrow spectrum activity against Gram +ve bacteria
 Resist Gastric acidity ,therefore can be given orally or injection in con-
trast to penicillin G given only by injection
 They have higher bactericidal activity than penicillin G
 Pharmacokinetics: highly absorbed from Intestine or site of I.M.injection
with high blood level concentration and highly distributed in tissues,
cerprosapinal fluid , Milk and urine.
 Uses. Bovine mastitis (chroni9c and acute) local or by injection and
some time given locally in combination with Neomycin or colistin in
cases of acute mastitis duo to infection with streptococci, staph. And
complicated with E.coli.
 B-Broad spectrum Penicillins
(Aminobenzyl penicillins)
 Ampicillin Amoxycillin
 They are the most important and common semisynthetic penicillins
used in Veterinary Practice as they have broad spectrum activity
against Gram positive and Gram negative bacteria.
 Have bactericidal activity in Vitro and in vivo against Streptococci,
Staphylococci, corynebacteria , clostridium spp., E.coli,, Salmonella,
klebsiella, Shigella, pasteuralla,
 Resistance :beta-lactamase producers bacteria are resistant to
Ampicillin and to less extent to Amoxycillin.
 Kinetics : they are rapidly absorbed from G.I.T and distributed in all
tissues and body fluids as well as after i.m. injection. They are
highly excreted in Urine, milk.
 Uses : 1. Poultry : Necrotic enteriitis, colienteritis
salmonelosis,colisepticaemia .
 Animals , Mastitis, pyogenic infections, pylonephritis ,pneumonia
 -Lactamase Inhibitor Combos
(Unasyn, Augmentin, Timentin, Zosyn)
Developed to gain or enhance activity against -lac-
tamase producing organisms (some better than oth-
ers). E.g Calvulanic acid or Sublactam Provides
some or good activity against:
Gram-positive Gram-negative
S. aureus (MSSA) H. influenzae
E. coli
Anaerobes Proteus sp.
Bacteroides sp. Klebsiella sp.
Neisseria gonorrhoeae
Moraxella catarrhalis
 Cephalosporins
• They also owe their activity to b-lactam ring and
are bactericidal.
• Produced from a fungus Cephalosporium acremo-
nium.
• Good alternatives to penicillins when a broad -
spectrum drug is required
• should not be used as first choice unless the or-
ganism is known to be sensitive
Classification and Spectrum of
Activity of Cephalosporins
• Divided into 4 major groups called “Gen-
erations”
• Are divided into Generations based on
 antimicrobial activity
 resistance to beta-lactamase
 Cephalosporins
• BACTERICIDAL- modify cell wall synthesis
• Interfere at the final step of peptidoglycan synthe-
sis ( Transpeptidation)
• CLASSIFICATION- first generation are early
compounds
• Second generation- resistant to β-lactamases
• Third generation- resistant to β-lactamases & in-
creased spectrum of activity
• Fourth generation- increased spectrum of activity
 First Generation Cephalosporins
Best activity against gram-positive aerobes,
with limited activity against a few gram-
negative aerobes
Gram-positive Gram-negative
meth-susc S. aureus E. coli
pen-susc S. pneumoniae K. pneumoniae
Group A/B/C/Gstreptococci P. mirabilis
viridans streptococci
FIRST GENERATION- eg cefadroxil, cefalexin, Cefadrine -
most active vs gram +ve cocci. An alternative to penicillins
for staph and strep infections; useful in UTIs
 Second Generation Cephalosporins
Spectrum of Activity(mainly against G-nega-
tive
Gram-positive Gram-negative
meth-susc S. aureus E. coli
pen-susc S. pneumoniae K. pneumoniae
Group A/B/C/G strep P. mirabilis
viridans streptococci H. influenzae
M. catarrhalis
Neisseria sp.
e.g cefoxitin and cephamandol
Second Generation Cephalosporins
Spectrum of Activity
The cephamycins (cefoxitin and cefotetan)
are the only 2nd generation cephalosporins
that have activity against anaerobes
Anaerobes
Bacteroides fragilis
Bacteroides fragilis group
Third Generation Cephalosporins
Spectrum of Activity
• In general, are even less active against gram-
positive aerobes, but have greater activity
against gram-negative aerobes
• Ceftriaxone and cefotaxime , Cephoperazone
have the best activity against gram-positive
aerobes, including pen-resistant S. pneumoniae
Third Generation Cephalosporins
Spectrum of Activity
Gram-negative aerobes
E. coli, K. pneumoniae, P. mirabilis
H. influenzae, M. catarrhalis, N. gonorrhoeae (including
beta-lactamase producing); N. meningitidis

Citrobacter sp., Enterobacter sp., Acinetobacter sp.

Morganella morganii, Serratia marcescens, Providencia

Pseudomonas aeruginosa (ceftazidime and cefoperazone)

Uses : M Pneumonia, metritis,nephritis , meteritis.cystis, foot
rot, septicemia and otitis.,
 Fourth Generation Cephalosporins
• 4th generation cephalosporins for 2 reasons
 Extended spectrum of activity
 gram-positives: similar to ceftriaxone
 gram-negatives: similar to ceftazidime, including Pseu-
domonas aeruginosa; also covers beta-lactamase produc-
ing Enterobacter sp.
against -lactamases; poor inducer of ex-
 Stability
tended-spectrum  -lactamases
• Only cefepime is currently available
Other classification of
Cephalosporins
 AMINOGLYCOSIDE & AMINOCYCLITOL
ANTIBIOTICS

Streptomycin (1944)
Dihydrostreptomycin
Neomycin (1949)
Kanamycin
Gentamicin (1963)
Spectinomycin
Apramycin

Gentamycin
The source of gentamicin was a strain of Micromonospora purpurea; the
spelling ending in “-micin” is to indicate that the source is not a Streptomyces
Aminoglucoside Antibiotics and Aminocyclitol
antibiotics

:Members

Streptomycin Neomycin
Gentamicin Kanamycin
Tobramycin Amikacin
Framycetin Paromomycin
 General considerations

1They are relatively broad spectrum bactericidal antibiotics but

act particularly in vivo against gram negative bacteria (E.coli,
Salmonella Spp,PasteurellaSpp,KlebisellaSpp,Pseudomonas
Spp(Genatmicin) and Tuberculus Spp(Streptomycin)

All inhibit the protein synthesis by acting at 30S-subumit 2

.ribosomal messenger of RNA

Resistance may occure due to R-Plasmid specified enzymes .3

-e.g. Adenyl transferase, acetyltransferase and phospho
trasnferase . Or chrosomal mutation(streptomycin)
All are poorly absorbed fron G.I.T, so they given by injection for sys- .4
temic use or locally either on skin (ointment or spray),orally in cases of
local enteritis and bacterial diarrhoea in animals and poultry and intra-
mammary in cases of mastitis or intrauterine in cases of meteritis

They have cummulative effect in kidneys and may cause NEPHROTXICITY .5

and also NEUROTXICITY (OTOTOXICITY) after long term adminiatration as
well as neuromuscular paralysis

Streptomycin and Dihydrostreptomycin .1

It is derived from moulds Streptomyces griseus and prepared in the form of

.streptomycin sulphate or dihydrostreptomycin
:ANTIMICROBIAL ACTIVITY
It is active mainly against G-ve bacteria and has some activity against Staph
aureus and Tuberculum bacilli(T.B.)
Mechanism of action

It inhibits the protein synthesis by preventing of amino acids

polymerization and causes misreading the correct amino acids
.for protein synthesis

:Bacterial resisitance

Due to either plasmid specified enzymes released by some bacte-

ria cause inactivation as adenyl transferase,acetyl transferase,
phosphotransferase, or chromosomal mutation or even de-
.crease cell wall permeability to streptomycin
NORMAL BACTERIA

w a ll
ce ll
e r ial
B act tRNA binds to the mRNA
ribosome complex
mRNA
30S

Rybosome tRNA

Elongation of the
peptide chain
Cyto- = Protein synthesis
plasma
 PHARMACODYNAMICS

ce ll
ia l
t er
B ac Binds to receptors
Tetracyclines wal
l
on the 30 S
Aminoglucosides 30S
mRNA

Rybosome tRNA
Active
carrier-mediated
transport INHIBITING BACTE-
RIAL PROTEIN SYN-
Cyto- THESIS
plasma
 Pharmacokinetic

It is poorly absorbrd from G.I.T (Low fat solubility , and*

. ionized)but it is rapidly absorbed from i.m. site of injection

It is distributed in body fluid and tissues except brain and cere-

.brospinal fluid and has low milk barrier after i.m. injection

.It is excreted mainly by kidneys and may cause nephrotoxicity

Therapeutic uses
Locally in bovine mastitis with a synergestic combination with .1
Penicillin-G to broaden the spectrum(100 mg/quarter in acute
.cases and 500 mg/quarter in dray mastitis
Locally in cases of gastroenteritis due to E.coli,salmonella(calf- .2
scour) usually combined with sulphonamides(20 mg/kg for 3 – 5
days)

By systemic injection (i.m.) in cases of pasteurellosis,vibriosis, .3

and usually in combination with peniciilin in cases of respiratory
infections (10 mg/kg every 12 hours for 3 days)

Toxicity
.A.Acute : Nasuea,vomition. Allrgy,hypersensitivity
B. Chronic: OTOTOXICITY. , chronic administration of streptomycin
leads to affaction of the 8th creanial nerve and causes auditory
impairment (deafness)

Nephrotoxicity
Streptomycin may cause renal dysfunction in high doses
Neuromuscular blocking effects( skeletal muscle paralysis)
Residues:
Streptomycin residues persists at the site of injection(muscle),
kidnys and milk.Veterinarians and farmers must obey the withdr-
.wal time before sloughtering or use of milk

Neomycin.2
Source: Streptomyces fradiae(a mixture of Neomycin A+B)
Anitmicrobial activity: Is mostly direected to the gram negative
, coliform bacteria , E.coli,SamonellaSpp
Shigella,proteus Spp., and S.aureus (in
.)vitro with BACTERICIDAL ACTIVITY
KINETICS: It is also poorly absorbed from GIT (3%) but highly
.absorbed from i.m.site of injection
After injection it reaches blood and can diffuse in
pleural and peritoneal cavities and brain
It excreted via kidneys after injection and completely
.in feces after oral administration
 Therapeutic uses

LOCALLY: Colienteritis in animal and poultry (oral) and given in

-combination with oxytetracycline in cases of pneumo
enteritis and salmonellosis

Coliform mastitis (intramammary with cloxacillin(acute

. and dry mastitis
TOPICALLY: skin burns,conjuctivitis,ulcerative dermatitis with
without cortisone
SYSTEMIC : Colisepticaemia,coli-urinary infection,respiratory
infections and SALMONELLOSIS in animals and
poultry
.Toxicity ; Like streptomycin
KANAMYCIN is Like NEOMYCIN
 Gentamicin(FORMULA).3
R1
HC-NH--R2 NH2
5 O 3 NH-- R3
4 I O II

O
NH2 HO OH
O
III
2 CH3
Gentamicin C1 HO NH-CH3
Gentamicin C2
Gentamicin C1a
Netilmicin

Gentamicin
”has been isolated for the first time in 1963 from the yeast “Micromonospora purpurea -
.is a mixture of minimum three closely related chemical structures -
Has the highest antibacterial activity and broadest spectrum from the group of aminoglycosides -
is used mainly for parenteral administration because of its low resorption from the intestines -
 Gentamicin.3

:ANTIBACTERIAL ACIVITY
It gas a bactericidal activity against most of gram negative bacteria and a
particular activity against klebiella Spp and Peseudomonas Spp as
well as Staph aureus. Its bactericidal mechanism likes other amino-
.glycosides
BACTERIAL RESISTANCE: Due to transmissible resistance
,Mechanisms (plasmid- mediated enzymes(inactivation) e.g
.Acetyltransferase,adenyltransferase and phosphotransferase

KINETICS: It is poorly absorbed from GIT but rapidly absorbed

after i.m. injection. It is widley distributed and excreted
mostly via kidneys(80%). It has a cummulative effect
by binding with renal cells(may cause nephrotoxicity
.It does not penitrate milk barrier
Uses: Like neomycin with doses of 3 – 5
.mg/kg b.wt
: TOXICITY: Long term therapy may result in
,NEUROTOXICITY,NEUROMUSCULAS RPARALYSIS
.and NEPHROTOXICITY
.It is contraindicated in cases of renal dysfunction
N.B. Gentamicin is not reccomended generally indi-
cated for use in food producing animals due to pro-
longed existance of it residues in muscles (90 – 120
days) and the long withdrawal time. But used Lo-
cally for treatement of mastitis in dairy animals, ene-
teritis in unweaned calves ,dog and cats
.No residues is following oral administration
 Aminocyclitol Antibiotics .4
e.g. Spectinomycin and apramycin

Spectinomycin
SOURCE: Streptomyces spectabilis
ANTIBACTERIAL ACTIVITY: It has bacteristatc activity against G-
ve bacteria e.g. E.coli,pasteurella spp.,Salmonella spp,and
,Mycoplasma Spp.( M.gallisepticum,M.synoviae,poultry strains
)M.bovis,cattle strains,M,capriae sheep and goat strains
Mycoplasmas spp cause CRD and CCRD in poultry , BRD in cattle
and ORD in sheep and goats. It has no effect on most G+ve
.bacteria
RESISTANCE: Chromasomal transmissble mutation and some
bacteria strans exhibit cross resistance with macrolide anitbi-
otics
Mode of action: likes other Aminoglucosides,
Interaction: Synergism between spectinomycin and lincomycin
against Mycoplasmas species
MYCOPLASMA

•Mycoplasma gallisepticum MG
•Mycoplasma synoviae MS

Causes: CRD
Complicated with Coli  CCRD
Kinetics: It is poorly absorbed from GIT,it is less penetratable to tissues
due to its fat solubility.It is distributed in extracelluar fluid following its
i.m. injection and not a barrier for milk.
.It is excreted in urine following its i.m.injection

;CLINICAL USES
Mycoplasmosis in Poultry (CRD,CCRD,given orally and.1
animals(BRD)pneumonia in sheep and goats, meteritis in cattel
and mare (given by i.m. route) IT IS COMMONLY GIVEN AS
COMBINATION WITH LINCOMYCIN TO PRODUCE A SYN-
ERGESTIC ACTIVITY AGAINST MYCOPLASM SPP AND TO
BROADEN THE SPECTRUM IN ANIMALSA AND POULTRY
Coliform mastitis in cattle and goats .2
Dose: 10 – 30 mg /kg for 3 – 5 days

N.B. Spectinomycin is contraindicated to be used in Laying hens

 APRAMYCIN

.Drived from streptomyces tenebraus..

It has bacteristatic effects on G-ve bacteria,E.coli, salmonellaspp ..
.proteus spp, klebiella spp
.It is poorly absorbed from GIT ..
It is rapidlt absorbed from i.m. site of injection and distributed ..
mostly in extracellular fluid and excreted unchanged in
.urine

USES: colibacellosis,salmonellosis, colienteritis in poultry and

calves and lambs .It is contraindicated to be used in cats
.)Toxic(
 TETRACYCLINES.5

Chlortetracycline
(Aureomycin)
Tetracycline
Oxytetracycline

Demethylchortetracycline

Minocycline

Methacycline

DOXYCYCLINE(Vibramycin)
 TETRACYCLINES.6

.SOURCE: Drived from streptomyces aureoficiens

.They are crystalline amphoteric substance
They are base in nature and mostly prepared as
hydrochloride and hydarte salts and not stable in room
temprature and exposure to light and able to chelete with
. heavy metals
:ANTIBACTERIAL ACTIVITY
BACTEISTATIC
Broad spectrum and active against
,some blood protozoa(anaplasma
)Babesia,Theileria
Moulds,yeast and fungi are resisitant
 SPECTRUM OF ACTIVITY
Gram postive Gram negative Protozoa Naked cells
Streptococcus, E. coli, Actinobacillus Actinomyces, Theileria, Mycoplasma
Staphylococcus, Klebsiella, Bordetella, Fusobacterium, Eperythrozoon,
Bacillus, Proteus, Brucella, Chlamydia, Anaplasma
Corynebacterium, Salmonella Haemophilus, Rickettsia
Erysipelothrix, Pasteurella,
Listeria Campylobacter,
Leptospira
Moderate
Sensitive Sensitive Sensitive Sensitive Sensitive
sensitive

Broad spectrum antibiotic effective

against Gram+, Gram- as well as My-
coplasma, spirochaetai Chlamydia and
Richettsia infections,some blood
Protozoa like Babesia and theileria.
Teteracyclines

High activity against CRD,CCRD,

Fowl Cholera,
Salmonellosis,Chalmydiosis
 PHARMACODYNAMICS
Mechanism of action

ce ll
ia l
t er
B ac Binds to receptors
l
wal on the 30 S
Tetracyclines 30S
mRNA

Rybosome tRNA
Active
carrier-mediated
transport INHIBITING BACTE-
RIAL PROTEIN SYN-
Cyto- THESIS
plasma
 PHARAMACODYNAMICS

General characteristics:
Quick bacteriostatic effect
Broad antibacterial spectrum (G- , G+ ) and Mycoplasmas
Synergism with other drugs
Possibility of resistance(a) Mutation,some bacteria can change their
Permeability to tetracycline (b) transmissible due to the transfere of
. R-plasmid

Mode of action:
Within the cell Tetracyclins binds with the 30 S ribosomal sub-unit
leading .to inhibition of the bacterial protein synthesis by preventing
the aminoacryl transfer RNA to the messenger-RNA complex (bacterio-
.static action)
 PHARMACOKINETICS
Oxytetracyclines are adequatly absorbed from GIT(mostly from --
the duedenal part).The absorbtion of doxycycline is greater
than oxytetracycline and chlortetracycline
Calcium salts and magnesium salts decrease the absorbtion of ---
,tetracyclines due to the chelation mechanism
Tetracyclines are absorbed from the site of im injection and -----
.produce pain,therefore they should be injected deeply i.m
Tetracyclines are highly distributed allover the body tissues ----
and able to pass blood brain barrier,C.S.F.,joints (lipophylic
Properties )and deposited in bone tissues as result to chelation
mechanism with calcium
They are excreted via kidneys(60%) and feces (biliary ---
.Excretion) as well as milk(good for treatment of mastitis
 Pharmacokinetics

Tissue Highly distributed

I.V

Mamammry
Kidneys
glands
.I.M
Blood

Oral Intestine Liver

-Entero
hapatic
Tissue diffusion of Tetracyclines
 Absorbtion

concentration
Oral ,i.m, Rectal drug
absorbtion
Tissue
.C max
t maxc. blood

Time
 Therapeutic uses

,They are given by all routes of administration (orally,injections

,Topical, intramammary
.Gastroenteritis(colienteritis, salomonellosis necrotic enteritis .1
Respiratory infections (pasteurolosis, .2
,mycoplasmosis ,CRD,CCRD ,BRD,ORD
Sytemic bacterial infections,speticaemia, urinary tract infections .3
reproductive tract infections(Endometritis, ,intrauterine ).i.m(
.Bolus). FOOT ROT(spray) arthritis
Bovine mastitis (intramammary,local) 5. Local treatment in cases of ker- 4
atoconjunctivitis(1% ointement)
.Cases of enzoatic abortion,leptospirosis, Brucellosis(i.m .6
.Injection),Haemophilus infection,chlamydiosis in sheep
Treatment aganst some blood parasites(Babesisis,Theierlosis and .7
Anaplasmosis(using LONG ACTING FORMULA,20Mg/ml +2 pyrilidone)

.Doses: 10 – 20 mg/kg b.wt

 USES IN POULTRY

Coibacillosis, infectious coryz, CRD and CCR

Nectrotic enteritis ,Pulorosis, Salmonellosis, chlamydiosis

Black head syndrom
Dosis 0.1 – 0.3 g per one liter of drinking water or 20 mg/kg b/wt/
.day for 3 – 5 days
 TOXICITY

.Acute: Nausia,vomition,diarrhoea,photosenitization.1

Chronic: Hepatic dysfunction,developing of growth fungi in .2

.mouth and GIT. ,Deposition in teeth
 6 M A C R O L ID E & L IN C O S A M ID E A N T IB IO T IC S

E r y th r o m y c in ( 1 9 5 2 )
O le n a d o m y c in ( 1 9 5 4 )
S p ir a m y c in
T y lo s in
L in c o m y s in ( 1 9 6 2 )
C lin d a m y c in

T y lo s in
A n t ib io t ic w it h a m a c r o lid e s t r u c t u r e is o la t e d f r o m a s tr a in o f
S t r e p t o m y c e s fr id ia e fo u n d in T h a ila n d

G r o u p o f a n t ib io t ic s w it h h ig h c h e m ic a l, b io lo g ic a l a n d t o x ic o lo g ic a l s im ila r it y .
 FORMULA
Formula: Tylosin tartrate
Tylosin is composed of 4 factors from which factor A is the most active. The
:other, less important factors are also determined
C46H88NO17(factor A) Tylosin
C39H65NO14(factor B) Desmycosine
C39H75NO17(factor C) Macrosine
C46H79NO17(factor D) Relomycine

Tylosin tartrate is described in the British Pharmacopoeia (Veterinary)

.1993
: Its composition is determined by HPLC and the pharmacopoeia describes that
the content of Tylosin A should be not less than 80% -
the total content of tylosin A,B, C and D should be not less than 95% -
:The Assay should be carried out by the Biological assay method for antibiotics
Tylosin should contain not less than 800 IU per mg -
 Macrolide and Lincosamide
Antibiotics
Members Molecular size
Lactoinic ring Oscidic
chain
Tylosin X XX
Erythromcin X XXX
Spiramycin X XX or XXX
Oleondomycin X XXX
Josamycin X X
Kitasamycin X X
 Antibacterial activity
They are acting against all strains of Mycoplasma species: M.gal-
lisepticum, M synoviae, of poultry
M.Capriae (goats),M,bovis (cattle) and other Mycoplasmas as well
.as all Gram positive bacteria

They have a bacteristatic effects

Plasmid mediated resistance --

Cross resistance may occure between -----
:Resistance
all members of macrolides due to the use of
subtherapeutic doses
 PHARMACODYNAMICS
mechnism of action
Bacteriostatic
Inhibition of protein
inhibition of
synthesis at 30 S
protein synthesisi
ribosomal subunit.
at 50 subunit
.

Mode of action

The activity of Macrolides is due to the interference with the

bacterial protein synthesis by binding to the 50 S ribosomal
sub-unit leading to inhibition of the bacterial protein synthesis
by preventing the aminoacryl transfer RNA to the messenger-
RNA complex (bacteriostatic action), Active at ribosomal level
by inhibiting the protein sysnthesis.

· Broad antibacterial spectrum (mainly G+,

Mycoplasmas,some G- (Camphylobacter coli, Chlamidia and
Spirochaetae ) possibility of resistance.
 Pharmacodynamic

Interaction with other drugs

, Synergism with Colistine.,neomycin

Antagonism with chloramphenicol or combination with bactericidal
products (penicillins, cefalosporins .)

Chemical incompatibilites

Alkalic solutions cause precipitation of Tylosin

Mixing with other drugs should be avoided
 PHARMOCOKINETICS
Macrolides are fat soluble,nonionised
And have small molecular size
Absorbtion

Oral ,GIT parenteral

complete (90 - 100 %) quick and complete (irritation)

Distribution

extracellular intracellular
good lipohylic (good solubility in fat)
Elimination

oral parenteral
95%bile and 5%urine -Entero Via kidney and bile

Hepatic
cycle
 FORMULA
Formula: Tylosin tartrate
Tylosin is composed of 4 factors from which factor A is the most active. The
:other, less important factors are also determined
C46H88NO17(factor A) Tylosin
C39H65NO14(factor B) Desmycosine
C39H75NO17(factor C) Macrosine
C46H79NO17(factor D) Relomycine

Tylosin tartrate is described in the British Pharmacopoeia (Veterinary)

.1993
: Its composition is determined by HPLC and the pharmacopoeia describes that
the content of Tylosin A should be not less than 80% -
the total content of tylosin A,B, C and D should be not less than 95% -
:The Assay should be carried out by the Biological assay method for antibiotics
Tylosin should contain not less than 800 IU per mg -
INDICATIONS
CALVES 
Pneumonia caused by Mycoplasma sp and
Pasteurella multocida sensitive to Tylosin.and other macrolides

Bovine mastitis 
Due to Mycoplasma bovis associated with
s.aureus,Streptococci,corynebacterium(oleondomycin)

Streptococcal infections,tonsilitis,naval ill, 

(Erthromycin).Otitis media
.

: Poultry 
Respiratory infections caused by Mycoplasma sp.
(CRD,CCRD),Susceptible to Tylosin.,sprirmycin,erythromycin as
. wellas Fowel cholera
 Lincosamides
(lincomycin)
Origin :streptomyces
ANTIBACTERIAL ACTIVITY: Bacteristatic in actvity, against
Mycoplasma spp, and gram positive
.bacteria
Resistance: Plasmid mediated resistance and cross
resistance with other macrolides
 PHARMACODYNAMICS
Antibacterial activity

Broad antibacterial spectrum < Mycoplasmas, some G- (Camphylobacter coli,

Chlamidia and Spirochaetae ) ans G+ e.g sterpt0cocci, Staphylococcusand
Clostridia Spp.
possibility of resistance.
Highest activity obtained within 2 to 4 hours after administration
The antibacterian activity is effective during growht‫ا‬
MIC
Most sensitive bacteria have MIC < 1 µg/ml
Not sensitive bacteria have MIC > 5 µg/ml
Bacterial resistance

Two types of resistance have been described

Acquired resistance: cross resistanve against the whole group
Induced resistance: by plasmid transfer
PHARMACODYNAMICS

Bacteriostatic
Inhibition of protein
synthesis at 50 S
ribosomal subunit.

Mode of action

The activity of Lincomycin is due to the interference with the bacterial pro-
tein synthesis by binding to the 50 S ribosomal sub-unit leading to inhibi-
tion of the peptidyl transferase enzyme. (bacteriostatic action)

Many gram-negative bacteria are resistant because their ribosomal binding

area is inpenetrable and methylated.
 PHARMOCOKINETICS
Resorption:
· quick and complete (T max = 1.5 hours) from GIT

Distribution:
· high volume distribution
· high concentration in extra-cellular liquids (high solubility in water),
· penetration of cells, tissues and other body fluids is high (lipohylic).
· tissue concentration 8 to 9 times higher than plasma concentrations
· Lincomycin remains longer in the lungs

Excretion:
· mainly excreted via liver and to a lesser degree via the urine.
· 8 hours after the last treatment Lincomycin cannot be detected any-
more in the plasma.
· Maximum in faeces after 8 hours (after 48 hours neglectable).
 INDICATIONS
. Used alone or with spectinomycin in
Cattle: Bovine respiratory diseses ,haemorrahagic
Septocaemia,mastitis ,endometritis,calf-diar-
rhoea,enterotoximeae
:Poultry
Mycoplasma spp. infections (M. gallisepticum, M. synoviae, M. mela-
gridis)
)CRD, airsacculitis(
Clostridia spp. infections (Clostridia perfringens)
)necrotic enteritis, necrotic dermatitis(
 POLYMYXINS

Polymyxin B

POLYMYXIN E (=colistin)

Polymixins are polypeptide antibiotics formed by fermentation of the aerobic spore-

forming Bacillus polymixa and Bacillus colistinus respectively

From 1947 to 1950 polymixins A, B, C, D, E and M were isolated. Chemically they

are closely related but only Polymixin B and E have been used clinically.

The polymixins are decapeptides having a molecular weight of approximately 1,200.

 Colistin
A narrow specrum antibiotic has bactericidal activity against
Gram negative bacteria like E.coli, Salmonella spp,Klebsiella spp
.Psudomonas spp
They have ther affaninty to in activate the endotoxins produced by
E.coli,salomonella (heat labile and heat stable toxins)

.Resistance: limited
.Kinetics: poorly absorbed from GIT (used for local infection e.g
enteritis, mastitis, local topical burnes
Interaction: synergitic activity with tetracyclines,penicillins
and macrolides and lincomycin
 MODE OF ACTION
:COLISTINE
binds to the bacterial cytoplasmic membrane 
reacts with phospholipids 
penetrates into cell membranes 
 disrupts the structure of the membranes

Bacterilysis !!!  Bacteria are killed

ACTION MECHANISM

Colistin

145
 SPECTRUM OF COLISTIN

Group Agent
Polymyxins Colistin
Penicillins Penicillin G
Tetracyclines Oxytetracycline
aminoglycosides Kanamycin
macrolides Tylosin
Chloramphenicols Chloramphenicol
Nitrofurans Furazolidone
Sulfonamides Sulfadimethxine
Others Carbadox
ONLY WHEN NECES-
!! SARY
Oral administration

 no detectable absorption from intestine

 short withdrawal time (0 days)

 neutralisation of toxins
 faster recovery

 only active against gram negative germs

 kills only the bad ones
 COLISTIN SULPHATE
Surface-active polymixin
)detergent dissolving the cell membrane =(
Neutralizes endotoxins of several Gram-
negative bacteria
FAST

Inhibits oxidative metabolism

Destroys the permeability of the bacterial cytoplasmic membrane

 Double action of colistin

NEUTRILIZE
BACTERICI-
OR ANTAGO-
ADAL ACTIV-
NIZE
ITY
-Entero- or Endo
E.Coli Strains Toxins produced
Salmonella Spp.
Pseudomonas Spp.
by E-Coli or
Klebsiella Spp. .Salmonella Spp
* Heat Labile Toxin.
* Heat Stable
NQ
Toxin.
RESISTANCE

Excellent Clini- International

cal Outcome in Pharmacologi-
Enteric infec-
cal and Clinical
tions with E-
Coli, Salmo- Concepts
nella
Possible combination of colistin with other an-
tibiotics in poultry

Amoxycillin Coli
b
Coli acillosis
en
Pull teritis
NEC Salm orosis
R Necr onello
teri t O T I C o ti c si s
Lincomycin is Co E n- E n te r i t
l i e nt is
eriti
s

My c o p l a
smosis
Tylosin
COLISTIN
Colienteritis

Doxycycline
o s i s ,Fowl
pl a s m
Myco holera
C
o n e ll osis, -
, Sa l m Coc
CCRD lienteritis i s) +
Co
nt e ri t
( Co l i e i os i s
ol i ci d
Anticoccidial E .C
 INDICATIONS
:Prevention and treatment( locally) of
:Salmonella and E.coli infections .1
diarrhoea in young animals and
poultry colienteritis enterotoxicamiae
Colimastitis (blue udder mastitis) with.2
Tetracylines or olendomycin(colifrom mastitis )
3. Infections by other sensitive bacteria like klesbiella
species and ,pseudomonas spp. Like skin burns with
neomycin and Bacetracin

4. Semen preservation as prophylactic against

contamination
 -Entero
Toxins
HLT
HST
Cholera
like

E.Coli
Under
.Elect
.
Microscope

.E.coli
colonies
Toxigenic strains isolated from blood of
baby chicks affected by coli septicaemia
: Systemic use
Urinary infections(E.coli,klebsiella spp
colibacillosis via intramuscular route
 CALVES AND LAMBS
.Diarrhoea due to infections by E. coli sp

Weakness

Diarrhoea
 POULTRY
Colisepticaemia (E. coli)
Air sacculitis, peritonitis, perihepatitis and pericarditis

Pullorum diarrhoea: white

 POULTRY
Pullorum disease in broilers
)Salmonella pullorum(
,Necrose of the heart muscle
lungs and stomac (muscle)
Peepers

White congelation
in caecum
 POULTRY

Fowl typhoid •
)Salmonella gallinorum(
Sleepy,eggs •

Swollen Spleen,
Brown liver
 CALVES AND LAMBS
.Diarrhoea due to infections by E. coli sp

Weakness

Diarrhoea
 Miscellanous antibiotics

.Chloramphenical,florphenicol.1
.Novobiocin.2
.Taimulin.3
.Bacteracin.4
Rifamycin.5
 Chlormaphenicol.1

:Chemical structure
NH-CO-CHCL2
NO2--- --- CH—CH—CH2OH
OH
Chloramphenicol

NH-CO-CHCL2
CH3SO2 --- CH—CH– CH2OH
OH Thiamphenicol

NH—CO—CHCL2
CH3SO2 --CH—CH—CH2---F
OH FLORPHENICOL
 Chloramohenicol

ORIGIN: natural(streptomyces venuzulae

.or synthetic ,maufactured as chlormaphenicol succinate
.It is highly stable

ANTIBACTEIAL ACTIVITY,Spectum
It a broad spectrum antibiotic ,acts against G-v and G+ve bacteria
With a bacteristatic type of action .It has special actvity against
.Most salmonella spp

:Resistance
R-Plasmid mediated resistance,inactivation
by acetyltransferase
Mode of action:It interferes with protein synthesis at 50 S-sub-
unit of ribosomal messenger of bacreial cells

N.B, Chloramphenicol als inhibits protein syn-

thesis of mammalian cells of bone marrow
(causes a plastic anaemia in small
Animals,children and baby chicks) but does
not affact the intact cells
 PHARMACOKINETICS

It is highly ,rapidly and completely absorbrd from GIT and site ++

of injection
.It is widely distributed allover the tissues C.N.S and C.S.F ++
and excreted mostly via urine and small amount via feces and
milk

uses
EMERGANCY
,Typhoid fever,paratyphoid(Salmonellosis)
Menegitis due to Haemophilus influenza(I.V.)
Local in cases of Conjunctivitis and cholienteritis
. with streptomycin
 Toxicity
Nausiam diarrhoea.1
Bone marrow disturbances (Interferes with R.B.Cs formation .2
.and causes a plastic anaemia(FETAL)
It interfers with some liver microsomal enzymes lead to rearda- .3
tion in growth as well as it prologes the duration of general
anaesthesia by interfers with the liver metabolic enzymes
inhibition
short acting medium acting
Barbiturates
of liver Barbiturates like
hours 3 – 1
metabolism hours 6 -4
It is restricted to be used in many counteries as Egypt 4
 FLORFENICOL
It is analogue of thiamphenicol and it is developed to
be used in animals
It substitute chloramphenicol to subside the toxicity cause by NI-
TROXYL group (NO2) as this group is substituted by
.Sulphonomethyl group(CH3SO2)

:Antibacterial
Broad activity agains G-Ve
specrum activity
and G+ve bacterioa like E.coli,Salmonella
spp. Pasteurellaspp.haemophilus influenza
Klebsiella etc…., it has greater antimicrobial actvity than chlo-
.ramphenicol
Bacterial Resistance is possibly not occures due to ther lack of
senstivity to the acetylase enzyme which destroys chloram-
.phenicol and thaimphenicol
Mechanism of action : likes chloramphenicol

.Pharmacokinetics: Likes chloramphenicol

Therapeutic uses
In cases of BRD (bovine Respiratory.1
diseases and other animals
cases of shipping fever and.2
haemorrahagic septicaemia
. colibacillosis,colienteritis ,diarrhoea
typhoid ,paratyphoid, due to
.salmonellosis
Fish bacterial diseases ,3