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CLINICAL USE OF

ANTIBIOTICS IN
VETERINARY PRACTICE
Submitted to: Dr. R.K. Bhardwaj, Dr. Ashok Kumar.
Submitted by: Amandeep Singh (J-12-BV-746)
5th Professional Year, B.V.Sc. & A.H.,
F.V.Sc. & A.H., SKUAST-J, R.S. Pura.
Objectives
To know about common antibiotics and their use in
clinical veterinary practice.
To know their pharmacological and toxicological
aspects.
To know about multiple drug interactions and drug-
body interactions.
Definitions
Antibiotics: It is a substance produced by a micro-
organism that at low concentration inhibit or kill other
micro-organisms.

Antimicrobials: These has broader definition than


antibiotic and includes any substance of synthetic, semi-
synthetic or natural origin which kill or inhibit the growth
of micro-organisms and cause little or no host damage.

Antibacterials: These are the compounds prepared


from naturally occurring organic or inorganic
compounds by their de novo synthesis are hence,
synthetic in origin. E.g. Sulphonamides and
Fluoroquinolones.
Spectrum of Activity
Based on three basic features

Class of micro- Narrow Spectrum (only bacteria)


Broad Spectrum (Mycoplasma,
organism Rickettesia, Chlamydia)

Antibacterial Narrow Spectrum (only gram positive)


Broad Spectrum (both gram negative
activity and gram positive)

Susceptibility Bacteriostatic (tetracycline, macrolides)


Bacteriocidal (-lactams,
of bacteria aminoglycosides)
Classification of antibiotics

1. Inhibition of cell wall 2. Inhibition of protein


synthesis. synthesis.
-lactams, Bacitracin Aminoglycosides, Tetracyclines,
Macrolides

Antibiotics

3. Damage to cell membrane 4. Inhibition of nucleic acid


function. synthesis.
Polymixins Nitroimidazoles, Nitrofurans,
Rifampin.
Antibiotic Drug Interactions
Additive/Indifferent Effect: if combined effect of
the drugs equal the sum of their independent
activities measured separately. E.g. 1+ 1 = 2.
Synergistic: if combined effects are significantly
greater than the independent effects. E.g. 1+ 1 >
2.
Antagonism: if combined effects are significantly
less than their independent effects. E.g. 1+ 1 = 0.
Potentiation: E.g. 1+ 0 = 2.
Synergism of Antibiotic Combinations

Sequential inhibition of cell wall synthesis. E.g.


Mecillinam + Ampicillin.
Facilitation of drug entry of one antibiotic by
another. E.g. -lactam + Aminoglycoside.
Inhibition of inactivating enzymes. E.g. Ampicillin +
Clavulanic Acid.
Prevention of emergence of resistant population.
E.g. Erythromycin + Rifampin.
Antagonism of Antibiotic Combination

Inhibition of bactericidal activity such as treatment


of meningitis in which a bacteriostatic drug prevents
the bactericidal activity of other drug.
Competition for drug binding sites. E.g. Macrolides
& Chloramphenicol.
Inhibition of cell permeability mechanism. E.g.
Chloramphenicol & Aminoglycoside.
Depression of resistance enzymes. E.g. third
generation Cephalosporins & -lactams.
Antibiotic Resistance

Constitutive
For Example: Inherent resistance of Enterobacteriaceae to Penicillin
G and gram positive to Polymixin B.
Acquired
It is of two types:
Chromosomal mutation to resistance: by changing target sites
(streptomycin, erythromycin), altering cell permeability
(chloramphenicol, tetracyclines), increasing production of
inactivating enzymes (-lactams).
Transferable drug resistance: (by extrachromosomal DNA) by
transduction (-lactamase gene), transformation (passage of DNA)
and conjugation (R-plasmid, responsible for MDR).

Cross Resistance: Aminoglycosides and Macrolides.


Control of Antibiotic Resistance
Administer drug at the therapeutic doses for short
period.
Use drugs in combination that prevent chromosomal
mutation and plasmid mediated resistance. E.g.
clavulanic acid.
Development of the policies related to antibiotics like
freely available, for special purposes only, and by
infectious diseases specialist.
Rotating the antibiotics in use, dont use any particular
antibiotic for more than 2 years.
Isolation of sick animals showing resistance.
Careful and appropriate use of antibiotics.
Principles of Antibiotic Drug Disposition
Routes of administration: PO, IM, IV, SC, IA, IU, etc.
Parentral therapy should always be used in case of acute
infections.
In horses, it is advisable to use antibiotics through oral route.
In treatment of susceptible gram negative bacteria, it is
advisable to use aminoglycosides through IM or SC route.
Peak plasma concentration in IM injection is after 15-30
minutes.
It is advisable to use oral therapy in young ones as the GIT
microflora and liver microsomal enzymes has not been
developed.
Poor oral absorption: aminoglycosides, Penicillin G,
erythromycin, so avoid oral use.
Factors Determining Choice of Antibiotics

Knowledge of susceptibility of
suspected pathogen.
Knowledge of factors that
affect drug concentration at
the site of infection.
Knowledge of drug toxicity
and factors that enhance it.
Cost of treatment.
Considerations of government
regulations about drug usage.

Choice of antibiotic
Bactericidal Bacteriostatic

Immunosuppression Severe infection Rest all other conditions


Corticosteroid Use along with Antibiotics

Their use is debatable. They have deleterious effects


if used with antibiotics however only on certain
conditions, they are indicated:
If severe life threatening septicemia, endotoxemia

and shock.
In severe, acute local infections to stabilize
lysozomal enzyme release from neutrophils resulting
in tissue destruction.
In cerebral edema due to complicated meningitis.
Indications for Combined Antimicrobial Treatment

When host defenses are impaired, mixed bacterial infections,


to prevent antibiotic resistance, to prevent enzymatic
degradation of drug, to minimize drug toxicity.
Clinically useful antimicrobial combinations
Indication Drug combination Comment
Bovine S. aureus mastitis Penicillin-streptomycin Synergistic combination
Bovine pastuerellosis, HS Ampicillin-sulbactam Synergistic combination
Rhodococcus equi pneumonia in foals Erythromycin-rifampin Synergistic combination
Brucella canis in dog Minocycline-streptomycin Synergistic combination
Peritonitis after intestinal spillage Gentamicin-clindamycin Broad-spectrum
antimicrobial activity
Cystitis caused by E.coli, Proteus, etc. Ampicillin-clavulanic acid Synergistic combination
Severe undiagnosed infection Amoxicillin-gentamicin Broad-spectrum and
synergistic combination
Failure of Antibiotic Therapy
Inappropriate use of antibiotic due to misdiagnosis.
Failure to culture infection.
Failure of lab tests and erroneous reports.
Antibiotic resistance by pathogens.
Intercellular location of bacteria.
Prophylactic Use of Antibiotics
Disease Drug Duration Comment
Feedlot pneumonia of Tetracycline, long acting Single dose Arrival at feedlot
calves
Dry cow therapy Many Single dose At last milking
Swine erysipelas Penicillin, long acting Single dose Pigs at risk
Leptospiral abortion in Streptomycin Single dose Remove carriers
cows
Strangles in horses Penicillin, long acting 1-3 doses Horses at risk
Pulpy kidney infection in Tetracycline Period at risk -
lambs

Important Notes:
Neomycin used to prevent post parturient metritis affects the fertility.
Gentamicin in mares reduces conception rates.
Tetracyclines given orally to feedlot calves causes mortality.
-lactam Antibiotics
Penam Penicillins
Discovered by Alexander Fleming in 1928.
Source: Penicillium notatum (mold)
MOA: inhibit the activity of transpeptidase and other
peptidoglycan active enzymes that are called as
penicillin binding proteins (PBPs) which are responsible
for formation of cell wall.
Have bactericidal nature on growing bacteria.
Resistance to -lactams is through production of
penicillinase enzyme that break -lactam ring of the
drug.
These are mostly effective against gram positive
bacteria.
Usual Dosages of Penicillins
Drug Route Dose Interval

Penicillin G, sodium IM IV 15-20,000 IU/kg 6-8 hours

Penicillin G PO 25,000 IU/kg 6 hours

Cloxacillin, oxacillin PO IM 40-60 mg/kg 8 hours

Ampicillin sodium IV IM 10-20 mg/kg 6-8 hours

Ampicillin PO 20-30 mg/kg 8 hours

Amoxicillin PO 20-30 mg/kg 8-12 hours

Amoxicillin trihydrate IM 10 mg/kg 12 hours


10% susp.
Benzyl Penicillin G
Clinical applications Infections caused by gram positive aerobes Streptococci,
Bacillus, Listeria, Corynebacteria, Erysipelothrix, anaerobic
Clostridia, spirochaete Borrelia (Lymes Disease),
Pastuerella.
Resistance Staph aureus by R plasmid
Pharmacokinetics Dry, crystalline form is stable, lose activity when dissolved
so fresh solution is prepared before every use, used
paretrally as it is acid labile.
Drug interactions Synergistic with aminoglycosides like streptomycin
(extended spectrum against gram negative), cloxacillin and
sulbactum.
Toxicities and side effects Check sensitivity before use. Cause immune mediated
hemolytic anemia in horses, cardiac arrest if potassium salt
is used IV (use sodium salt). Dont give procaine penicillin
through IV as it causes nervous excitement, give IM.
Penicillinase Resistant Penicillins
Methicillin, Oxacillin, Cloxacillin, Nafcillin

Mainly used in the treatment of bovine staphylococcal


mastitis.
They are acid stable and can be given orally in case of
skin infections in dogs.
Methicillin should not be stored for longer times as it
deteriorates rapidly.
Ampicillin-cloxacillin combinations have been used
successfully for treating bovine mastitis as they have
synergistic activity.
A single topical instillation of benzithine cloxacillin into
conjunctival sac is effective in treatment of Moraxella
bovis keratoconjunctivitis in cattle.
Broad Spectrum Penicillins
Ampicillin, Amoxicillin

Clinical applications Ampicillin is best penicillin for the treatment of


urinary tract and enteric infections caused by
susceptible organisms. Ampicillin and amoxicillin are
drugs of choice for leptospirosis and listeriosis. Used
orally in salmonellosis, Klebsiella, E. coli infections.
Resistance Plasmid mediated; E.coli, S. typhimurium, S. aureus
Pharmacokinetics Acid stable. Bioavailability for amoxicillin is 60-70%
and for ampicillin 20-30%.
Drug interactions Ampicillin is synergistic with aminoglycosides for both
gram positive and gram negative bacteria. Sulbactam
and clavulanic acid show remarkable synergism (
lactamase inhibitors).
Toxicities and adverse effects Disturbance of normal intestinal flora on oral use. Large
doses are contraindicated in horses as they may
disturb microflora in colon of horse. Ampicillin is
contraindicated in small rodents and rabbits.
Cephalosporins
Source: Cephalosporium acremonium
Mostly given through parentral injections.
Have short have life except ceftriaxone.
They are bactericidal, relatively non-toxic, can be
used in penicillin sensitive animals.
The resistance is of constitutive type due to presence
of cephalosporinases in periplasmic space of
bacterial cell.
Classification
On the basis of antimicrobial activity, -lactamase stability and pharmacological properties
Group Microbiology Standard Other
cephalosporins cephalosporin
Orally active Fairly active against gram positives, Cefacholr, cefadroxil, Cephaloglycin.
modest against gram negatives and cephadrine, cephalexin.
none against Pseudomonas.
Parentral
Group I Highly active gram positives, Cefapirin,
moderate -lactamase producing cephalothin,
gram neagtives, none Pseudomonas cephazolin.
Group II High activity against cefotaxim, ceftiofur, Ceftriaxone
Enterobacteriaceae cefuroxime. (prolonged T1/2).
Group III High activity Pseudomonas and Cefsulodin, Cefoperazone
related organisms. ceftazidime. (Biliary excretion).
Group IV Greatest stability to -lactamases, Cefoxitin, Cefotetan
prominent activity against Bacteroids moxalactam. (prolonged T1/2).
Orally Administered Cephalosporins
Cephachor, cefadroxil, cephradine, cephalexin

Clinical Nonspecific infections caused by Staphylococci, Streptococci,


applications Enterobacteriaceae, used for treating abscesses and wound
infections. Long term use (30 Days) for chronic pyoderma in
dogs. Cephalexin is drug of choice for K. pneumoniae, urinary
tract infections.
Resistance Acquired; Enterobactriaceae
Pharmacokinetics Completely absorbed after oral administration, have half life of
1-2 hrs, poor absorption in horses and ruminants.
Drug interactions Oral cephalosporins are potentially synergistic with
aminoglycosides.
Toxicities and Vomition and diarrhea may occur in very less proportion of
adverse effects animals, sometimes cross reactive with penicillin.

Species Drug Dose Interval (Hours)


Dog, Cat Cefadroxil 22mg/kg 8
Calves Cefadroxil 35mg/kg 12
Group I Parentral Cephalosporins
Cefapirin, cephradine, cephalothin, cephazolin, cephalexin

Clinical Most useful in penicillin resistant Staph aureus or gram positive


applications infections in penicillin allergic patients. Parenral treatment of
Staph aureus in horses. Prophylaxis of surgical wound in
humans. Prevention and treatment of mastitis.
Resistance Acquired; MRSA (Methicillin Resistant Staph aureus)
Pharmacokinetics IM or SC injection results in high bioavailability. Rapidly excreted
but can be retained in the body by using probenecid.
Drug interactions Group I cephalosporins are synergistic with aminoglycosides.
Toxicities and Drug can induce thrombophlebitis if given IV, nephrotoxicity at
adverse effects very high doses.

Species Drug Dose Interval (Hours)


Dog, Cat Cephalexin 10-15mg/kg 12
Cephazoline 15-30mg/kg 12
Horses Cephapirin 20mg/kg 8
Group II Parentral Cephalosporins
Cefotaxim, ceftriaxone, ceftiofur, cefuroxime

Clinical It should be reserved for serious life threatening situations. Drug


applications of choice in meningitis caused by E. coli and Klebsiella. Used in
bone and joint infections, septicemias, soft tissue infections,
lower respiratory tract infections, etc.
Resistance Transferable, plasmid mediated resistance.
Pharmacokinetics Not absorbed PO, used parentrally. Half life is upto 1 hour except
ceftriaxone (8 hours) as it goes biliary excretion.
Drug interactions Group II cephalosporins are synergistic with aminoglycosides,
cefotaxime with quinolones.
Toxicities and Ceftriaxone may cause coagulopathies which may be revesed by
adverse effects Vitamin K.

Species Drug Dose (mg/kg) Interval (Hours)


Dog, Cat Cefotaxime 20-40 (IM), 50 (SC) 8-12
Ceftriaxone 25 24
Cattle Ceftiofur 1 8
Ceftriaxone 6-11 12
Group III Parentral Cephalosporins
Cefoperazone, cefsulodin, ceftazidime

Clinical Largely reserved for human medicine for P. aeruginosa and other
applications gram negatices. Cefoperaazone used for bovine coliform mastitis.
Resistance Not yet present.
Pharmacokinetics Hepatic metabolism leads to GIT problems in human subjects.
Drug interactions Group III cephalosporins are synergistic with aminoglycosides.
Toxicities and Contraindicated in horses and other herbivores with expanded
adverse effects bowel.

Species Drug Dose (mg/kg) Interval (Hours)


Dog, Cat Cefoperazone 30 6-8
Cattle Cefoperazone 30 6-8
-lactamase inhibitors
Clavulanic acid, sulbactam

Clavulanic acid Sulbactam


Combined with amoxicillin in Sulbactam is usually combined
ratio 2:1 and is bactericidal. with ampicillin and
Clavulanic acid is well absorbed
cefoperazone.
PO with mild GIT upset in dogs, It is poorly absorbed orally and
cats. well absorbed IM.
Used for empirical treatment of The ampicillin and sulbactam
UTIs in dogs and cats at dose combination should not be used
rate of 12.5mg/kg in dogs and in herbivores with extended
62.5mg/cat. bowel.
Dont administer PO to Clinically used for respiratory
ruminants and parentrally to problems in bovines
horse, rabbits. (Pastuerellosis), Actinomycosis,
Injection for cattle and sheep is
neonatal calf diarrhea, E. coli
available and dose rate is meningitis in calves at the dose
8.75mg/kg IM. rate of 8 mg/kg IM/IV.
Polymixins
Source: Bacillus polymyxa
Discovered in 1940s and great activity against P.
aeruginosa.
Colistin is polymixin E and is available as sulfate salt for
oral administration and sulfomethate for parentral use.
Polymixin B is available as sulfate for both purposes.
MOA: Polymyxins are cationic surface acting agents
that disrupt the structure of cell membrane
phospholipids and increase cell permeability, thereby
producing a cidal effect on bacteria especially gram
negative bacteria.
Contd...
Clinical Oral treatment of E. coli, Salmonella, parentral treatment of
applications coliform mastitis, local treatment of P. aeruginosa such as otitis
externa, superficial eye infections and skin infections as an
ointment or solution of polymyxin B.
Polymyxin + neomycin = chronic otitis externa.
Resistance Cross resistance among polymixins.
Pharmacokinetics Very slowly absorbed, parentral preparations should be given IM,
daily dose should not exceed 5mg/kg BW and only be used for 5
days parentrally.
Drug interactions Synergistic with SLDs + TMP, Amphoterecin B, EDTA and
chlorhexidine are often used in the topical preparations.
Toxicities and Have nephrotoxic, neurotoxic and neuro-muscular blocking
adverse effects effects. Nephrotoxicity is aggrevated by aminoglycosides if used in
combination. Contraindicated in renal injury.
Administration Polymyxin B = 2.5mg/kg BW IM (dont give IV) & 5mg/kg BW PO
and dosage at 12 hour intervals.
Colistin sulfomethate = 3mg/kg BW IM at 12 hour intervals.
Glycopeptides
Vancomycin

Fermentation product of Streptomyces orientalis.


Bactericidal to most gram positives esp. cocci.
Drug of choice for the oral treatment of Clostridium difficile
colitis because of its activity and narrow bactericidal
spectrum.
MOA: inhibit synthesis of cell wall by binding to D-alanyl D-
alanine terminal of muramyl decapeptide.
Available as HCl salt and synergistic with aminoglycosides.
Irritating to tissues, so always given IV. Rapid IV injection
release histamine and cause Red-Neck Syndrome in humans
and is highly ototoxic.
Administered at the dose rate of 20mg/kg IV at 12 hours
interval diluted with 200ml 5% dextrose and 5-10 mg/kg
BW PO.
Aminoglycosides & Aminocyclitols
Bactericidal with specific activity against aerobic bacteria and
Mycoplasma.
The problems of toxicity especially to branches of 8th cranial nerve
and to kidneys have not been overcome.
They remain useful for their activity against gram negative bacteria
including P. aeruginosa and Staphylococci and their synergism with
penicillins.
They are also called as aminocyclitols as they consist of hexose
nucleus to which amino sugars are attached by glycosidic likage.
MOA: they bind to 30s ribosomal subunit where it induces
misreading of the genetic code on mRNA template and there by
inhibit protein synthesis.
In potency, spectrum of activity and stability to enzymes, the order
of activity is as follows:
Amikacin > tobramycin >= gentamicin > neomycin = kanamycin > streptomycin
Contd...
Relative risk of toxicity of different aminoglycoside
at usual dosage
Drug Vestibular Toxicity Cochlear Toxicity Renal Toxicity
Streptomycin +++ ++ +
Neomycin + +++ +++
Kanamycin + ++ ++
Amikacin + + +
Gentamicin ++ + ++
Tobramycin + + +
Streptomycin
Clinical Drug of choice for C. fetus subsp. veneralis, Y. pestis, F. tularensis, M.
applications tuberculosis in combination with other drugs. Alone used for
treating leptospirosis. Along with penicillin, used for treatment of
brucellosis, wooden tongue, other pyogenic wounds and
abscesses.
Resistance By plasmid specific enzymes.
Pharmacokinetics These are not absorbed orally, impaired renal function delay their
excretion time and also cause renal toxicity, so before using it, renal
function should be determined.
Drug interactions Synergistic with cell wall acting antibiotics like penicillins.
Toxicities and Cause vestibular damage and effect increases with cumulative dose.
adverse effects Cats are very sensitive to streptomycin. At high doses cause
neuromuscular blockage, nystagmus and ataxia.
Administration 8-12 mg/kg IM; repeat after 12 hours.
and dosage
Neomycin
Clinical Treatment of enteric infections, skin infections and treatment of
applications wounds. It is majorly used for treatment of neonatal E. coli
diarrhea in calves.
Resistance Plasmid mediated resistance.
Pharmacokinetics Same as that of streptomycin, several times more active than
streptomycin. In horses, it impairs the response of neutrophils,
therefore, its use is not advocated.
Drug interactions Synergistic with lactams, bacitracin and macrolides for treating
infections caused by gram positives.
Toxicities and Most toxic of aminoglycosides and readily cause ototoxicity and
adverse effects permanent deafness, if used IM or PO. Severe tubular necrosis in
cats.
Administration It is often reserved for topical infections and combined with
and dosage bacitracin.
10 mg/kg PO, repeat after 6 hours for enteric infections.
Amikacin
Chemically modified kanamycin

Clinical Reserved for use in infections caused by gram negative aerobes.


applications It is used extensively in horses for endometritis, lower respiratory
tract infections esp. K. pneumoniae and Pseudomonal infections. In
dogs, it can be used for UTIs, skin and soft tissue infections.
Resistance Hospital mediated resistance in gram negative bacteria.
Pharmacokinetics Same as that of other aminoglycosides but it has been observed
that it decreases the GFR and have late renal clearance in foals.
Drug interactions Synergistic with lactams especially azlocillin and ticarcillin.
Toxicities and It is ototoxic and nephrotoxic but the frequency of these effects are
adverse effects low. Monitoring of renal function during treatment is recommended.
Administration Dogs, Cats: 10mg/kg IM, SC, repeat after 8-12 hours.
and dosage Horses: 4-8 mg/kg IM, repeat after 8-12 hours.
Gentamicin
Obtained form Micromonospora purpurea

Clinical Most active aminoglycoside and has the broadest spectrum of


applications activity. Greatly used against Enterobactriaceae and P. aeruginosa.
It is parentral drug of choice for coliform mastitis. Can be used in
salmonellosis, E. coli septicemia. In foals, it is drug of choice for
gram negative septicemia, R. equi pneumonia, infectious metritis in
mares, superficial and ulcerative keratitis. Also used for
infections of joints and bones.
Resistance Hospital mediated resistant usually Pseudomonas.
Pharmacokinetics Same as that of classic aminoglycoside but comparatively it has
larger volume of distribution in young animals which indicates that
high doses is required by the young ones as compared to adults.
Drug interactions Synergistic with lactams, SLDs. Antagonism occur with
chloramphenicol, macrolides and tetracyclines.
Toxicities and Neuromuscular blockade, potentially nephrotoxic. Intra-uterine
adverse effects infusions should be avoided as it decreases conception rate.
Administration Dogs, cats: 4-6 mg/kg IM, Slow IV; repeat after 8-12 hours.
and dosage
Lincosamides
Lincomycin and clindamycin

Source: Streptomyces lincolensis var. lincolensis.


Bacteriostatic antibiotic, particularly active against
gram positive bacteria and Mycoplasma.
MOA: inhibit protein synthesis by binding to 50s
ribosomal subunit and inhibiting peptidyl
transferase enzyme.
Moderate spectrum drugs as the gram negative
bacteria are resistant to these drugs.
Clinical Staphylococcal and streptococcal dermatitis, osteomyelitis,
applications arthritis, mastitis. Clindamycin has excellent activity against
anaerobes, used for treatment of toxoplasmosis. Used for
periodontal and pyogenic infections of skin and soft tissues in
dogs.
Resistance Plasmid mediated resistance is stable and more common. MLS
(Macrolide, Lincosamide, Streptogramin) cross resistance is
present.
Pharmacokinetics Highly lipid soluble, absorbed from the intestine of herbivores.
Penetrate well in prostrate, eyes and udder. Clindamycin achieve
effective concentration in bones.
Drug interactions Clindamycin synergistic with aminoglycosides and metronidazole.
Antagonism with macrolides and chloramphenicol.
Toxicities and Severe diarrhea in horses, rabbits and other herbivores resulting
adverse effects in psuedomembranous colitis leading to shock and death. Highly
toxic to guinea pigs, hamsters and very low doses cause fatal
typhilitis.
Administration Lincomycin HCl:15-20mg/kg PO, 10-20mg/kg IM IV; repeat after
and dosage 12 hours.
Clindamycin HCl phosphate: 5-11mg/kg PO, 3-5mg/kg IM IV;
repeat after 8-12 hours.
Macrolides
Basically macrocyclic lactones.
Efficacy is higher against Campylobacter,
Chlamydia and Mycobacteria.
Used PO, however IM preparations are also
available.
MOA: inhibit protein synthesis by binding to 50s
ribosomal subunit. Inhibit translocation step.
They are bacteriostatic at low concentrations and
bactericidal at high concentrations.
Erythromycin
Clinical Drug of choice to treat Campylobacter jejuni dirrhea or abortion
applications and to treat R. equi in foals. Alternative to ampicillin and
amoxicillin in treatment of leptospirosis and to tetracyclines in
Rickettsial infections.
Resistance Plasmid mediated resistance is common. Cross resistance with
lincosamides.
Pharmacokinetics Prolonged half life, large volume of distribution, high intercellular
concentrations.
Drug interactions Combination of erythromycin with lincosamides, other
macrolides and chloramphenicol is antagonistic.
Toxicities and Severe pain on IM injection as they are irritants. IV injection may
adverse effects lead to thrmbophlebitis. If given in high doses, have stimulatory
effect on GI smooth muscles and leads to diarrhea.
Administration Erythromycin estolate: 10-20mg/kg PO; repeat after 8 hours.
and dosage Erythromycin lactobionate: 3-5mg/kg IM IV; repeat after 8 hours.
Tylosin
Isolated from Streptomyces fradiae

Clinical In cattle: pneumonia, foot rot, metritis, pink eye, mastitis.


applications In swine: atophic rhinitis, pastuerellosis, growth promoter.
In dogs: treating abscesses, pneumonia, tracheobronchitis.
In poultry: CRD, spirochetosis.
Resistance Plasmid mediated resistance is common. Cross resistance with
lincosamides.
Pharmacokinetics Highly lipid soluble and is a weak base, half life is 1 hour. Tylosin
tartrate readily absorbed by intestine but tylosin phosphate poorly
absorbed.
Drug interactions Synergistic with SLDs to treat upper respiratory tract infections.
Toxicities and Irritant to tissues. IM injection in pigs lead to edema, pruritis,
adverse effects edema of rectal mucosa, and mild anal protrusion. Tylosin and
spiramycin have induced contact dermatitis in veterinarians.
Tylosin is contraindicated in horses.
Administration 20-30mg/kg IM except horses and pigs; repeat after 8-12 hours.
and dosage
Newer Macrolide Antibiotics
Roxithromycin is acid stable derivative of
erythromycin which is better absorbed after oral
administration and longer half life (13 hours).
Clarithromycin is also a derivative of erythromycin
which is twice as active against bacteria than
erythromycin and greater activity against M. avium.
Azithromycin is acid stable with more activity
against Haemophilus influenzae. It is evaluated as
single oral dose treatment for genital chlamydiosis
in humans.
Tetracyclines
Chlortetracycline, oxytetracycline, tetracycline, doxycycline, minocycline

Source: Streptomyces aureofaciens (Chlortetracycline), S.


rimosus (Oxytetracycline).
Slightly soluble in water.
Bacteriostatic antibiotics.
Available as HCl in wide variety of dosage forms.
The solutions are acidic with exception of chlortetracycline.
MOA: irreversibly bind to 30s ribosomal subunit where they
interfere with binding of aminoacyl transfer RNA and inhibit
protein synthesis.
These are classic broad spectrum antibiotics and inhibit
bacteria, Mycoplasma, Chlamydia, Rickettsia and some
protozoa.
Minocylcine, which is highly lipid soluble have greatest
of the activity among tetracyclines.
Contd...
Resistance Plasmid mediated and acquired resistance.

Pharmacokinetics In dogs and cats, mostly absorbed through GIT. With exceptions of
doxycycline and minocycline, the absorption of tetracycline is
decreased by the presence of food. They undergo enterohepatic
circulation which imparts them high half life (6-10 hours). Tissue
irritation is caused by the IM injection of the drug.
Drug interactions Synergism of tetracycline with tylosin for treating pasteurellosis,
doxycycline and rifampin or streptomycin for treating brucellosis.
Toxicities and Irritant nature cause tissue irritation, disturbance of intestinal
adverse effects flora, ability to bind with calcium and magnesium (CV effects,
deposition on teeth and bones), severe renal tubular damage.
Never use expired or degenerated preparation. In horses,
tetracyclines leads to colitis X by suppression of intestinal
microflora. They also have anti-anabolic effect which may lead to
azoturia in horses.
Species Dosage form Route Dose Interval Comments
(mg/kg) (hour)
Dogs, cats Tetracycline, oxytetracycline IV IM 10 12
Doxycycline IV 5-10 12
Horses Oxytetracycline IV 3-5 12 Slow IV
Ruminants Tetracycline, oxytetracycline IV IM 10 12-24 Slow IV
Long acting tetracycline IM 20 48
Pigs Same as ruminants IM injection
Chlortetracycline Oral 10-30 24
Clinical Applications
Cattle, Treatment of bovine pneumonias, lower respiratory tract diseases, clostridial
sheep infections and listeriosis. Oxytetracycline is drug of choice in anaplasmosis and
and Q-fever. Treatment and vaccination against bovine heart water disease by Cowdria
goats ruminatium and in treatment of keratoconjunctivitis.
Swine Atophic rhinitis and infections of lower respiratory tract.
Horses Drugs of choice for Potomac horse fever, ehrlichiosis.
Dogs, Drugs of choice for ehrlichiosis, rickettsial infections. Minocycline is affective in
cats combination with streptomycin against brucellosis. UTIs caused by P. aeruginosa.
Cats suffering from chalmydia and upper respiratory tract infections.
Poultry Chlamydiosis, CRD, infectious synovitis, fowl cholera.
Miscellaneous Antibiotics
Monensin
Ionophore antibiotic

Clinical Used to control coccidiosis ion poultry and to improve feed


applications efficiency in other animals. Can be used to prevent abortions due
to toxoplasmosis, swine dysentry and hemorrhagic enteropathy
in pigs.
Source Streptomyces cinnamonensis
MOA Complexes with sodium in the cell membrane to cause passive
transport of potassium across cell membrane and kill the bacteria.
It changes the ruminal flora to more gram negative which help in
better feed conversion by producing more propionate.
Drug interactions Synergistic with lactams, bacitracin and macrolides for treating
infections caused by gram positives.
Toxicities and Highly toxic to horses. Muscle weakness and myoglobinuria are
adverse effects most common to horse, dogs, pigs and sheep in case of toxicity.
Cardiac myopathy occurs in cattle and animal dies with
generalized heart failure.
Administration 11-33ppm of feed PO to cattle.
and dosage 15-25ppm of feed PO to swine.
Fusidic Acid
Steroidal antibiotic

Source: Fusidium coccineum.


Available as a sodium salt.
MOA: it inhibits protein synthesis by inhibiting the
binding of aminoacyl tRNA to the ribosomal A site.
It is mainly active against gram positive bacteria and
have bactericidal activity against Staph aureus.
It is mainly used PO for treatment of Staph aureus
infections.
Synergism with corticosteroids and used in the treatment
of severe pruritis.
System Specific Antibiotics
Antimicrobial Drug Selection in Infection of Horses
Site Suggested Drug
Upper respiratory Procaine penicillin G
tract
Lung Penicillin G, erythromycin
GIT Cephalosporins, ampicillin, tetracyclines, erythromycin
Soft tissue Penicllin G, ampicillin, aminoglycosides, oxytetracycline
Bone and joint Tetracyclines, cephalosporins, gentamicin
Skin Procaine penicillin G, ampicillin.
Renal Penicillin G, oxytetracycline, ampicillin
Cardiovascular Penicillin G and aminoglycosides
system
Nervous system Third generation cephalosporins, oxytetracycline, penicillin G
Eye Gentamicin, tetracycline, bacitracin + polymixin + neomycin mixture.
Reproductive tract Penicillin G, ampicillin, amikacin, gentamicin, neomycin, potassium
penicillin.
Mastitis Penicillin G and aminoglycosides.
Antimicrobial Drug Selection in Infection of Canines
Site Suggested Drug
Skin and subcutis Penicillins, lincosamides, macrolides, amoxicillin-clavulanic acid
Ear Topical polymixins, aminoglycosides, amoxicillin-clavulanic acid
Eye Topical neomycin+polymixin, gentamicin, amoxicillin
Respiratory tract Amoxicillin, tetracycline, penicllin G, aminoglycosides, lincomycin
GIT Ampicillin, amoxicillin, macrolides, lincosamides, tetracycline
Urinary and genital Ampicillin, amoxicillin, macrolide, amoxicillin-clavulanic acid
Musculoskeletal Amoxicillin, isoxazolyl penicillin, lincosamides, gentamicin
Nervous system Amoxicillin-clavulanic acid, lincosamides, tetracycline
Antimicrobial Drug Selection in Infection of Felines
Site Suggested Drug
Skin and subcutis Penicillins, lincosamides, amikacin, amoxicillin-clavulanic acid
Ear Topical polymixins, aminoglycosides
Eye Topical tetracycline, amoxicillin-clavulanic acid
Respiratory tract Amoxicillin-clavulanic acid, penicllin G, penicillin V, macrolides
GIT Ampicillin, amoxicillin, macrolides, lincosamides, erythromycin
Urinary and genital Ampicillin, amoxicillin, macrolide, amoxicillin-clavulanic acid
Musculoskeletal Amoxicillin, isoxazolyl penicillin, lincosamides, gentamicin
Nervous system Ampicillin, cephalosporins, penicillin G, amoxicillin.
Antimicrobial Drug Selection in Infection of Cattle
Site Suggested Drug
Respiratory Oxytetracycline, pencillin G, ceftiofur, erythromycin
GIT Penicillin G, oxytetracycline, sulbactam-ampicillin
Skin and conjunctiva Penicillin G, oxytetracycline, sulbactam-ampicillin
Genital IU penicillin, cephalosporins, tetracyclines, Penicillin G
Musculoskeletal Penicillin G, oxytetracycline
CNS Ceftiofur, Penicillin G, oxytetracycline, sulbactam-ampicillin
Urinary Penicillin G, oxytetracycline
Cardiovascular Penicillin G, oxytetracycline
Mastitis Gentamicin, third generation cephalosporins, penicillin G,
erythromycin, tylosin, cloxacillin, tetracyclines.
Antimicrobial Drug Selection in Infection of Sheep and Goats
Site Suggested Drug
Reproductive Tetracycline, penicillin G, monensin, streptomycin
Systemic Oral amoxicillin, penicillin G, cephalosorins, aminoglycosides
Repiratory Tetracycline, lincomycin, tylosin, penicillin G
Integument Oxytetracycline, penicillin G
Foot Streptomycin, lincomycin, long acting tetracycline.
Mammary glands Cloxacillin, aminoglycosides, tylosin, tetracycline
Urinary Penicillin G, oxytetracycline
Antimicrobial Drug Selection in Infection of Swine
Site Suggested Drug
Skin Procaine penicillin G, ampicillin, lincomycin
Locomotor system Procaine penicillin G, lincomycin, tylosin
Nervous system Procaine penicillin G, penicillin V, aminoglycosides
Respiratory Tetracycline, ampicillin, penicillin G
Urogenital Streptomycin, tetracyclines, ampicillin, lincomycin, neomycin
GIT Gentamicin, ampicillin, penicillin G, lincomycin
Cardiovascular Tetracycline, oxytetracycline
Antimicrobial Drug Selection in Infection of Poultry
Site Suggested Drug
Respiratory Erythromycin, lincomycin, tylosin, tetracycline
Soft tissue, septicemia penicillin+streptomycin, tetracycline, neomycin
GIT Tetracycline, aminoglycosides, lincomycin, neomycin
For Further Reading
1. Antimicrobial Therapy in Veterinary Medicine 2nd Ed.,
by John F. Prescott & J. Desmond Baggot.
2. Veterinary Pharmacology and Toxicology by B.K. Roy.
3. A Textbook of Veterinary Clinical Medicine by
Amalendu Chakrabarti.
4. Essential Drugs edited by Jacques Pinel, 2013 Ed.,
published by World Health Organization.
5. Incidence of Drug Interactions in Veterinary Critical
Care Patients by Katherine Larson; Spring, 2002 Honors
Thesis; Washington State University.
6. Drug Interactions by Stockley, 5th Ed., Pharmaceutical
Press; London, 1999.
THANK YOU FOR LISTENING WITH PATIENCE.

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