Antibiotics In Veterinary Use y1s1h

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 

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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 drugbody interactions.

Definitions 

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Antibiotics: It is a substance produced by a microorganism that at low concentration inhibit or kill other micro-organisms. Antimicrobials: These has broader definition than antibiotic and includes any substance of synthetic, semisynthetic 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 microorganism

• Narrow Spectrum (only bacteria) • Broad Spectrum (Mycoplasma, Rickettesia, Chlamydia)

Antibacterial activity

• Narrow Spectrum (only gram positive) • Broad Spectrum (both gram negative and gram positive)

Susceptibility of bacteria

• Bacteriostatic (tetracycline, macrolides) • Bacteriocidal (ß-lactams, aminoglycosides)

Classification of antibiotics 1. Inhibition of cell wall synthesis. ß-lactams, Bacitracin

2. Inhibition of protein synthesis. Aminoglycosides, Tetracyclines, Macrolides

Antibiotics 3. Damage to cell membrane function. Polymixins

4. Inhibition of nucleic acid synthesis. Nitroimidazoles, Nitrofurans, Rifampin.

Antibiotic Drug Interactions 

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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 

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Sequential inhibition of cell wall synthesis. E.g. Mecillinam + Ampicillin. Facilitation of drug entry of one antibiotic by another. E.g. ß-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 

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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 & ß-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 (ß-lactams). • Transferable drug resistance: (by extrachromosomal DNA) by transduction (ß-lactamase gene), transformation (age of DNA) and conjugation (R-plasmid, responsible for MDR).

Cross Resistance: Aminoglycosides and Macrolides.

Control of Antibiotic Resistance 

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ister 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, don’t 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  

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Routes of istration: 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 

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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 Immunosuppression

Severe infection

Bacteriostatic 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.

Indication

Clinically useful antimicrobial combinations 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 calves

Tetracycline, long acting

Single dose

Arrival at feedlot

Dry cow therapy

Many

Single dose

At last milking

Swine erysipelas

Penicillin, long acting

Single dose

Pigs at risk

Leptospiral abortion in cows

Streptomycin

Single dose

Remove carriers

Strangles in horses

Penicillin, long acting

1-3 doses

Horses at risk

Pulpy kidney infection in lambs

Tetracycline

Period at risk

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.

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ß-lactam Antibiotics

Penam Penicillins   

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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 ß-lactams is through production of penicillinase enzyme that break ß-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 10% susp.

IM

10 mg/kg

12 hours

Benzyl Penicillin G Clinical applications

Infections caused by gram positive aerobes Streptococci, Bacillus, Listeria, Corynebacteria, Erysipelothrix, anaerobic Clostridia, spirochaete Borrelia (Lyme’s 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). Don’t give procaine penicillin through IV as it causes nervous excitement, give IM.

Penicillinase Resistant Penicillins Methicillin, Oxacillin, Cloxacillin, Nafcillin 

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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 (ß 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    

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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, ß-lactamase stability and pharmacological properties

Group

Microbiology

Standard cephalosporins

Other cephalosporin

Orally active

Fairly active against gram positives, modest against gram negatives and none against Pseudomonas.

Cefacholr, cefadroxil, Cephaloglycin. cephadrine, cephalexin.

Group I

Highly active gram positives, moderate ß-lactamase producing gram neagtives, none Pseudomonas

Cefapirin, cephalothin, cephazolin.

Group II

High activity against Enterobacteriaceae

cefotaxim, ceftiofur, cefuroxime.

Ceftriaxone (prolonged T1/2).

Group III

High activity Pseudomonas and related organisms.

Cefsulodin, ceftazidime.

Cefoperazone (Biliary excretion).

Group IV

Greatest stability to ß-lactamases, prominent activity against Bacteroids

Cefoxitin, moxalactam.

Cefotetan (prolonged T1/2).

Parentral

Orally istered Cephalosporins Cephachor, cefadroxil, cephradine, cephalexin Clinical applications

Nonspecific infections caused by Staphylococci, Streptococci, 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 istration, have half life of 1-2 hrs, poor absorption in horses and ruminants.

Drug interactions

Oral cephalosporins are potentially synergistic with aminoglycosides.

Toxicities and adverse effects

Vomition and diarrhea may occur in very less proportion of 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 applications

Most useful in penicillin resistant Staph aureus or gram positive 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 adverse effects

Drug can induce thrombophlebitis if given IV, nephrotoxicity at very high doses.

Species

Drug

Dose

Interval (Hours)

Dog, Cat

Cephalexin Cephazoline

10-15mg/kg 15-30mg/kg

12 12

Horses

Cephapirin

20mg/kg

8

Group II Parentral Cephalosporins Cefotaxim, ceftriaxone, ceftiofur, cefuroxime Clinical applications

It should be reserved for serious life threatening situations. Drug of choice in meningitis caused by E. coli and Klebsiella. Used in bone and t 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 Ceftriaxone

20-40 (IM), 50 (SC) 25

8-12 24

Cattle

Ceftiofur Ceftriaxone

1 6-11

8 12

Group III Parentral Cephalosporins Cefoperazone, cefsulodin, ceftazidime Clinical applications

Largely reserved for human medicine for P. aeruginosa and other 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 adverse effects

Contraindicated in horses and other herbivores with expanded bowel.

Species

Drug

Dose (mg/kg)

Interval (Hours)

Dog, Cat

Cefoperazone

30

6-8

Cattle

Cefoperazone

30

6-8

ß-lactamase inhibitors Clavulanic acid, sulbactam Clavulanic acid  Combined with amoxicillin in ratio 2:1 and is bactericidal.  Clavulanic acid is well absorbed PO with mild GIT upset in dogs, cats.  Used for empirical treatment of UTIs in dogs and cats at dose rate of 12.5mg/kg in dogs and 62.5mg/cat.  Don’t ister PO to ruminants and parentrally to horse, rabbits.  Injection for cattle and sheep is available and dose rate is 8.75mg/kg IM.

Sulbactam  Sulbactam is usually combined with ampicillin and cefoperazone.  It is poorly absorbed orally and well absorbed IM.  The ampicillin and sulbactam combination should not be used in herbivores with extended bowel.  Clinically used for respiratory problems in bovines (Pastuerellosis), Actinomycosis, neonatal calf diarrhea, E. coli meningitis in calves at the dose rate of 8 mg/kg IM/IV.

Polymixins  

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Source: Bacillus polymyxa Discovered in 1940s and great activity against P. aeruginosa. Colistin is polymixin E and is available as sulfate salt for oral istration 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 applications

Oral treatment of E. coli, Salmonella, parentral treatment of 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. istration and dosage

Polymyxin B = 2.5mg/kg BW IM (don’t give IV) & 5mg/kg BW PO at 12 hour intervals. Colistin sulfomethate = 3mg/kg BW IM at 12 hour intervals.

Glycopeptides Vancomycin 

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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 Dalanine 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. istered 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 

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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

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Relative risk of toxicity of different aminoglycoside at usual dosage Drug

Vestibular Toxicity Cochlear Toxicity

Renal Toxicity

Streptomycin

+++

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+

Neomycin

+

+++

+++

Kanamycin

+

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++

Amikacin

+

+

+

Gentamicin

++

+

++

Tobramycin

+

+

+

Streptomycin Clinical applications

Drug of choice for C. fetus subsp. veneralis, Y. pestis, F. tularensis, M. 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. istration and dosage

8-12 mg/kg IM; repeat after 12 hours.

Neomycin Clinical applications

Treatment of enteric infections, skin infections and treatment of 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 ß 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. istration and dosage

It is often reserved for topical infections and combined with bacitracin. 10 mg/kg PO, repeat after 6 hours for enteric infections.

Amikacin Chemically modified kanamycin Clinical applications

Reserved for use in infections caused by gram negative aerobes. 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 ß 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. istration and dosage

Dogs, Cats: 10mg/kg IM, SC, repeat after 8-12 hours. Horses: 4-8 mg/kg IM, repeat after 8-12 hours.

Gentamicin Obtained form Micromonospora purpurea Clinical applications

Most active aminoglycoside and has the broadest spectrum of 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 ts 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 ß 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. istration and dosage

Dogs, cats: 4-6 mg/kg IM, Slow IV; repeat after 8-12 hours.

Lincosamides Lincomycin and clindamycin  

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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 applications

Staphylococcal and streptococcal arthritis, mastitis. Clindamycin has anaerobes, used for treatment of periodontal and pyogenic infections dogs.

dermatitis, osteomyelitis, excellent activity against toxoplasmosis. Used for of skin and soft tissues in

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. istration and dosage

Lincomycin HCl:15-20mg/kg PO, 10-20mg/kg IM IV; repeat after 12 hours. Clindamycin HCl phosphate: 5-11mg/kg PO, 3-5mg/kg IM IV; repeat after 8-12 hours.

Macrolides  

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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 applications

Drug of choice to treat Campylobacter jejuni dirrhea or abortion 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. lincosamides.

Cross resistance with

Pharmacokinetics Prolonged half life, large volume of distribution, high intercellular concentrations. Drug interactions Combination of erythromycin with lincosamides, macrolides and chloramphenicol is antagonistic.

other

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. istration and dosage

Erythromycin estolate: 10-20mg/kg PO; repeat after 8 hours. Erythromycin lactobionate: 3-5mg/kg IM IV; repeat after 8 hours.

Tylosin Isolated from Streptomyces fradiae Clinical applications

In cattle: pneumonia, foot rot, metritis, pink eye, mastitis. In swine: atophic rhinitis, pastuerellosis, growth promoter. In dogs: treating abscesses, pneumonia, tracheobronchitis. In poultry: CRD, spirochetosis.

Resistance

Plasmid mediated resistance is common. lincosamides.

Cross resistance with

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 dermatitis in veterinarians. Tylosin is contraindicated in horses. istration and dosage

20-30mg/kg IM except horses and pigs; repeat after 8-12 hours.

Newer Macrolide Antibiotics 

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Roxithromycin is acid stable derivative of erythromycin which is better absorbed after oral istration 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 

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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 (mg/kg)

Interval (hour)

Comments

Dogs, cats

Tetracycline, oxytetracycline Doxycycline

IV IM IV

10 5-10

12 12

Horses

Oxytetracycline

IV

3-5

12

Slow IV

Ruminants

Tetracycline, oxytetracycline Long acting tetracycline

IV IM IM

10 20

12-24 48

Slow IV

Pigs

Same as ruminants Chlortetracycline

IM injection Oral

10-30

24

Clinical Applications Cattle, sheep and goats

Treatment of bovine pneumonias, lower respiratory tract diseases, clostridial infections and listeriosis. Oxytetracycline is drug of choice in anaplasmosis and Q-fever. Treatment and vaccination against bovine heart water disease by Cowdria 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, cats

Drugs of choice for ehrlichiosis, rickettsial infections. Minocycline is affective in 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 applications

Used to control coccidiosis ion poultry and to improve feed 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 ive 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 ß 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. istration and dosage

11-33ppm of feed PO to cattle. 15-25ppm of feed PO to swine.

Fusidic Acid Steroidal antibiotic   

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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 tract

Procaine penicillin G

Lung

Penicillin G, erythromycin

GIT

Cephalosporins, ampicillin, tetracyclines, erythromycin

Soft tissue

Penicllin G, ampicillin, aminoglycosides, oxytetracycline

Bone and t

Tetracyclines, cephalosporins, gentamicin

Skin

Procaine penicillin G, ampicillin.

Renal

Penicillin G, oxytetracycline, ampicillin

Cardiovascular system

Penicillin G and aminoglycosides

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.

2. 3.

4.

5.

6.

“Antimicrobial Therapy in Veterinary Medicine” 2nd Ed., by John F. Prescott & J. Desmond Baggot. “Veterinary Pharmacology and Toxicology” by B.K. Roy. “A Textbook of Veterinary Clinical Medicine” by Amalendu Chakrabarti. “Essential Drugs” edited by Jacques Pinel, 2013 Ed., published by World Health Organization. “Incidence of Drug Interactions in Veterinary Critical Care Patients” by Katherine Larson; Spring, 2002 Honors Thesis; Washington State University. “Drug Interactions” by Stockley, 5th Ed., Pharmaceutical Press; London, 1999.

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