Antibiotics in Veterinary Medicine

Antibiotics in Veterinary Medicine

The ability of an antimicrobial drug to arrest the growth of or kill bacteria is dependent upon its mechanism of action and the concentration that the drug attains at the infection site. When a drug is introduced into the body, it is rapidly carried through the bloodstream to the liver, kidneys, and other organs that can chemically change or reduce its antibacterial activity and promote its excretion.

These processes of drug (1) absorption from its site of administration, its subsequent (2) distribution throughout the body and its elimination by (3) biochemical metabolism, and (4) excretion through the urine, bile, or other routes are pharmacokinetic parameters collectively given the acronym ADME. These variables are dependent both on the patient and on the physicochemical features and other properties of the antimicrobial drug.

This chemical and physiological processing by the body, as well as the lipid solubility and other chemical properties of the drug, affect the ability of the drug to penetrate infected tissues and make contact with pathogens that reside in interstitial fluids or host cells. The early exposure of pathogenic bacteria to effective drug concentrations for an optimum period of time is directly associated with the clinical success of antimicrobial drug therapy.

The tables below illustrate the veterinary importance of these antibiotics. The links provide additional drug information.

Aminoglycosides

Mode of Action Inhibition of protein synthesis. Once inside the bacterial cell, aminoglycosides bind to the 30s ribosomal subunit and cause a misreading of the genetic code. This subsequently leads to the interruption of normal bacterial protein synthesis.
Example Gentamicin, tobramycin, amikacin, streptomycin, kanmycin
Source Streptomyces spp.
Microsmonospora spp.
Spectrum of Activity Broad spectrum but not effective against anaerobic bacteria
Effect on bacteria Bactericidal (dose dependent)
Examples of applications in veterinary medicine Due to its toxicity, aminoglycoside use has been clinically limited to severe infections. The more toxic antibiotics in this class have been restricted to topical or oral use for the treatment of infections caused by Enterobacteriaceae. The less toxic aminoglycosedes are used for parenteral treatment of severe sepsis cause by Gram-negative aerobes.
Miscellaneous Nephrotoxic and ototoxic; not effective against anaerobic bacteria.

Link to Wikipedia for more information on aminoglycosides

ß-Lactam Antibiotics

Mode of Action Inhibition of cell wall synthesis. This particular group is characterized by its four-membered, nitrogen-containing ß-lactam ring at the core of their structure, which is key to the mode of action of this group of antibiotics. ß-lactam antibiotics target the penicillin-binding proteins or PBPs, a group of enzymes found anchored in the cell membrane, which are involved in the cross-linking of the bacterial cell wall. The ß-lactam ring portion of this group of antibiotics binds to these different PBPs, rendering them unable to perform their role in cell wall synthesis. This then leads to death of the bacterial cell due to osmotic instability or autolysis.
Examples Penicillins: Natural: penicillin G, penicillin V; Penicillinase-resistant penicillin: methacillin, oxacillin, nafcillin; Extended-spectrum penicillin: ampicillin, amoxicillin, carbenicillin

Cephalosporins: cephalothin, cefamandole, cefataxime

Carbapenems: primaxin

Monobactams: aztreonam
Source Penicillin: Penicillum chrysogenum (syn: P. notatum), Aspergillus nidulans

Cephalosporin: Acremonium chrysogenum (syn: Cephalosporium acremonium), Paecilomyces persinicus, Streptomyces clavuligerus, Nocardia Lactamdurans, Flavobacterium sp. Lysobacter lactamgenus
Spectrum of Activity Broad-spectrum: carbapenems, 2nd, 3rd, and 4th generation cephalosporins

Narrow spectrum: penicillin, 1st generation ecphalosporins, monobactams
Effect on bacteria Generally bactericidal
Examples of applications in veterinary medicine

Ruminants: anthrax, listeriosis, leptospirosis, clostridial and corynebacterial infections; streptococcal mastitis, keratoconjuntivitis

Swine: erysipelas, streptococcal and clostridial infections

Horses: tetanus, strangles, other strep and clostridial infections, foal pneumonia

Dogs and cats: streptococcal and clostridial infections, UTI

Poultry: necrotic enteritis, ulcerative enteritis, and intestinal spirochetosis

Miscellaneous Although ß-lactam antibiotics should theoretically work against all types of bacteria, this is not the case. This is because different bacteria have varying PBP content and nature. Also, some bacteria have natural structural characteristics which does not favor this mode of action (Gram-negatives have an outer membrane layer which makes the PBPs more difficult to reach).

Link to Wikipedia more information on ß-Lactam antibiotics

Chloramphenicol

Mode of Action Inhibition of protein synthesis. Chloramphenicol irreversibly binds to a receptor site on the 50S subunit of the bacterial ribosome, inhibiting peptidyl transferase. This inhibition consequently results in the prevention of amino acid transfer to growing peptide chains, ultimately leading to inhibition of protein formation.
Spectrum of activity Broad spectrum
Effect on bacteria Bacteriostatic
Examples of applications in veterinary medicine

Because of its capacity to cause fatal aplastic anemia in humans, chloramphenicol is prohibited in food animals in the US and many countries.

May be considered for some anaerobic infections in companion animals, such as serious ocular infections, prostatitis, otitis media/interna and salmonellosis.

Miscellaneous

Causes bone marrow depression and may compromise antibody production if given prior to vaccination.

Anaphylaxis, vomiting, and diarrhea have been reported in dogs and cats, the latter being more likely to be susceptible to toxicity.

Link to Wikipedia for more information about Chloramphenicol

Fluoroquinolones

Mode of Action Inhibition of nucleic acid synthesis. Fluoroquinolones have been shown to bind to the DNA gryrase-DNA complex and interrupt a process that leads to the negative supercoiling of bacterial DNA. This disruption leads to defects in the necessary supercoiling, and render the bacteria unable to multiply and survive.
Examples Enrofloxacin, ciprofloxacin, Danofloxacin, Difloxacin, Ibafloxacin, Marbofloxacin, Pradofloxacin, Orbifloxacin
Source Synthetic
Spectrum of activity

Broad spectrum: 3rd-generation fluoroquinolones

Narrow spectrum: other fluoroquinolones

Effect on bacteria Bactericidal
Examples of applications in veterinary medicine

Ruminants: acute respiratory disease, infections with E. coli, Salmonella, Mycoplasma, mastitis, metritis, conjuntivitis

Swine: treatment of infections cause by Mycoplasma hyopneumoniae, Actinobaccillus pleuropneumoniae, Escherichia coli, and Pasteurella multocida. Should never be administered in feeds because residues can contaminate the environment; prohibited for use in pigs in some countries.

Horses: for infections with bacteria resistant to the first drug of choice; not recommended in young growing horses (may cause cartilage erosion)

Dogs and cats: prostatitis, mastitits, rhinitis, pyoderma, otitis, wound infections, peritonitis, osteomyelitis, and soft tissue infections; not recommended for use in animals < 8 months of age (or < 18 months of age for large breed dogs to avoid arthropathoc effects).

Miscellaneous Available formulations or approved use in different animal species vary widely between countries; sometimes extralabel use, but may be prohibited in some countries.

Link to Wikipedia for more information on Fluoroquinolones

Glycopeptides

Mode of action Inhibition of cell wall synthesis. Glycopeptides bind to precursors of cell wall synthesis which leads to interference of the penicillin-binding protein (PBP) enzymes such as transpeptidases to incorporate the precursors into the growing cell wall. With this, cell wall synthesis stops and cell death often follows.
Example Vancomycin, teicoplanin, avoparcin
Source Various species of actinomycetes such as Streptomyces orientalis (vancomycin), Nocardia actinoides (Actinoidin)
Spectrum of activity Narrow spectrum affecting only Gram-positive bacteria
Effect on bacteria Bactericidal
Examples of applications in veterinary medicine

Vancomycin: "last resort" drug in human medicine with very few applications in animals.

Avoparcin: used extensively for growth promotion of chickens and pigs.

Miscellaneous

Ristocetin, although bactericidal like vancomycin, was discontinued for use as an antibiotic because it causes aggregation of blood platelets. However, this unfavorable attribute was put to good use in helping to diagnose von Willebrand's disease.

Some glycopeptides, like avoparcin, A4696 or actaplanin, and A35512, are being marketed and used as feed additive in some countries. When it became apparent that avoparcin selected for VRE (vancomycin resistant enterococci) in animals, Denmark, and subsequently all of Europe, withdrew it from animal feeds to reduce risk for humans. The ban in Denmark was reportedly followed by an immediate decrease in VRE isolates in poultry, but not in pigs, until tylosin was also banned from use in feed (Aerestrup et al., 2001).

Link to Wikepedia for more information on Glycopeptides

Lincosamides

Mode of Action Inhibition of protein synthesis. Lincosamides bind to the 50S ribosomal subunit and inhibit peptidyl transferases.
Example Lincomycin, Clindamycin, and Pirlimycin
Source Streptoyces lincolnensis subsp. lincolnensis
Spectrum of activity Moderate-spectrum; they are primarily active against Gram-positive bacteria, most anaerobic bacteria, and some mycoplasma.
Effect on bacteria Can be bactericidal or bacteriostatic, depending on the drug concentration, bacterial species and concentration of bacteria.
Examples of applications in veterinary medicine

General: clindamycin has an excellent activity against anaerobes

Swine: lincomycin is used extensively in the prevention and treatment of dysentery and sometimes in mycoplasma infections

Cattle: used as intramammary infusion in mastitis (pilrimycin)

Horses: should not be used in horses

Dogs and Cats: for infections with Gram-positive cocci and anaerobes

Poultry: for the control of mycoplasmosis (usually in combination with spectinomycin) and necrotic enteritis

Miscellaneous Should not be used in horses.

Link to Wikipedia for more information on Lincosamides

Macrolides

Mode of action Inhibition of protein synthesis. Macrolides reversibly bind to 50S subunit of the ribosomes and inhibit transpeptidation and translocation processes, resulting in premature detachment of incomplete polypeptide chains.
Examples Macrolides approved for veterinary use: Erythromycin, Tylosin, Spiramycin, Tilmicosin, Tulathromycin
Source

Saccharopolyspora erythaea (Erythromycin)

Streptomyces fradiae (Tylosin)

Some are semisynthetic (Tilmicosin, Tulathromycin)

Spectrum of activity Narrow spectrum
Effect on bacteria Generally bacteriostatic, but may be bactericidal at high concentrations or if there is a low number of a highly susceptible bacterial organism.
Examples of applications in veterinary medicine

Erythromycin: drug of choice against Campylobacter jejuni. Can be an alternative to penicillin in penicillin-allergic animals and second choice for anaerobic infections.

Tylosin and spiramycin: used against Mycoplasma infections; used as growth promotants.

Tilmicosin: against Mannheimia, Actinobaciullus, Pasteurella, Mycoplasma.

Miscellaneous

Parenteral use of tylosin in horses has been fatal, while oral administration has no indication for use and might result in enterocolitis.

Tilmicosin can be fatal to pigs if given parenterally and is not recommended for use in goats due to toxicity.

Link to Wikipedia for more information on Macrolides

Polymixins

Mode of action Inhibition of cell membrane function. Disrupt the structure of cell membrane phospholipids and increase cell permeability by a detergent-like action, causing cell death. This binding is competitive with calcium and magnesium. Polymixins have also been shown to neutralize endotoxins.
Example Polymixin B, colistin (Polymixin E)
Source Bacillus polymyxa

Spectrum of activity

Narrow spectrum affecting primarily Gram-negative bacteria
Effect on bacteria Bactericidal
Examples of applications in veterinary medicine

Cattle: colibacillosis and salmonellosis in calves, mastitis

Swine: neonatal porcine colibacillosis

Horses: bacterial keratitis or metritis caused by Klebsiella spp.

Dogs and cats: bacterial keratitis, otitis externa, skin infections

Miscellaneous Polymixins are not absorbed from the gastrointestinal tract. Because of their excessive nephrotoxic nature, other polymixin classes have been discarded.

Link to Wikipedia for more information on Polymixins

Rifamycins

Mode of action Inhibition of nucleic acid synthesis. Enters neutrophils and macrophages and inhibits DNA-dependent RNA polymerase in bacteria
Example Rifampin, Rifabutin, Rifapentine
Source Amycolaptosis mediterrainei
Spectrum of activity Broad spectrum; also has antiviral and antifungal activity
Effect on bacteria Bactericidal
Add-ons Rifampin is used as a first-line oral drug treatment for tuberculosis in humans

Link to Wikipedia for more information on Rifamycins

Streptogramins

Mode of action Inhibition of protein synthesis. Streptogramins irreversibly bind to the 50S ribosomal subunit. Group A streptogramins prevent peptide bond formation during chain elongation step, while group B components cause the release of incomplete peptide chains from the 50S ribosomal subunit.
Example Virginiamycin
Source Streptomyes virginiae.

Spectrum of activity

Narrow spectrum; mainly Gram-positive bacteria
Effect on bacteria

Group A or Group B - Bacteriostatic

Group A and Group B - Bacteriocidal

Examples of applications in veterinary medicine Used largely as a growth promotant for livestock, but has also been used to prevent laminitis in horses.
Miscellaneous Virginiamycin has been developed largely as a growth promoter and is still used in many countries. It has been banned by European Union since 1999.

Link to Wikipedia for more information on Streptogramins

Sulfonamides

Mode of action Inhibition of other metabolic processes. Sulfonamides interfere with folic acid synthesis by preventing addition of para-aminobenzoic acid (PABA) into the folic acid molecule through competing for the enzyme dihydropteroate synthetase.
Example Sulfadiazine, sulfamethoxazole, sulfadoxine
Source Synthetic
Spectrum of activity Broad-spectrum; affects Gram-positive and many Gram-negative bacteria, toxoplasma and protozoal agents
Effect on bacteria Bacteriostatic
Add-ons Act synergistically (and becomes bactericidal) in combination with diaminopyrimidines (trimethoprim)

Link to Wikipedia for more information on Sulfonamides

Tetracyclines

Mode of action Inhibition of protein synthesis. Once tetracyclines have been transported into the cell, this class of antibiotic reversibly binds to receptors on the 30S ribosomal subunit of the bacteria, preventing attachment of aminoacyl-tRNA to the RNA-ribosome complex. This in turn prevents the addition of amino acids to the elongating peptide chain, thus preventing synthesis of proteins.
Example Chlortetracycline, oxytetracycline, demethylchlortetracycline, rolitetracycline, limecycline, clomocycline, methacycline, doxycycline, minocycline
Source Streptomyces spp.; some are also semisynthetic
Spectrum of activity Broad spectrum. Exhibits activity against a wide range of Gram-positive, Gram-negative bacteria, atypical organisms such as chlamydiae, mycoplasmas, rickettsiae, and protozoan parasites.
Effect on bacteria Bacteriostatic
Examples of applications in veterinary medicine Tetracyclines are primarily indicated in the treatment of borreliosis, brucellosis (usually in combination with rifampin or streptomycin), chlamydiosis, ehrlichiosis, leptospirosis, listeriosis, rickettsiosis, and tularemia.
Miscellaneous Tetracyclines have also been used for nonantibacterial purposes, having shown properties such as anti-inflammatory activity, immunosuppression, inhibition of lipase and collagenase activity, and wound healing.

Link to Wikipedia for more information on Tetracyclines

Diaminopyrimidines (Trimethoprim)

Mode of action Inhibition of other metabolic processes. Trimethoprim interferes with folic acid pathway by binding the enzyme dihydrofolate reductase.
Example Trimethoprim, Aditoprim, Baquiloprim, Ormetoprim
Source Synthetic
Spectrum of activity Broad spectrum; affects Gram-positive and many Gram-negative bacteria
Effect on bacteria Bacteriostatic
Add-ons Act synergistically (and becomes bactericidal) in combination with sulfonamides

Link to more information on Diaminopyrimidines (Trimethoprim)