BETA LACTAM ANTIBIOTICS

- Possess beta lactam ring: responsible for the antibacterial property

- Kills bacteria by inhibiting formation or weakening the cell wall (transpeptidation)
- Binds to penicillin-binding proteins (PBP’s)
- Have better therapeutic to toxic effect ratio
- Enhanced antibacterial spectrum
- Bactericidal against gram-
positive microorganisms in a time
dependent manner
- First Beta lactam antibiotics
a. Penicillin G
b. Cephalosporin C
c. Monobactam
d. Carbapenem
Why gram-positive bacteria?

Mechanism of Action
- Bactericidal
- Disrupt bacterial cell wall by binding to a
variety of proteins (responsible for cell wall
synthesis) → death and lysis of bacterial
cells
- Penicillin binding proteins (PBPs)
o Specific target of beta lactam
o Involved in
 Terminal stages of bacterial cell
wall assembly
 Reshaping cell wall during
growth and division
o Examples
o Transpeptidases
o Cross-linking of the threads thus strengthens the peptidoglycan layer → weakening
of the cell wall → bacteria continues to grow → increase osmotic pressure →
rupture and death
o Carboxypeptidases
o Endopeptidases
 o Rupture is due to intracellular hypertonicity
- Beta-lactamases
o Secreted by gram-positive bacteria extracellularly
o Gram-negative: periplasmic space
- To be effective:
o 1st: penetrate the lipopolysaccharide outer membrane of cell wall
o 2nd: combine with PBPs on inner cell wall (avoiding beta-lactamases)
- Effectivity in Gram-negative bacteria
o Associated with the rate of antibiotic penetration
o Addition of aminobenzyl side chain to penicillin (ampicillin) improves activity
o Amoxicillin (aminobenzyl group): better penetration
- Difference in activity between Gram positive and Gram negative is the thickness of the
outer layer exterior to the peptidoglycan layer
- Gram-negative bacteria: impermeable outer membrane is the major mechanism for
resistance (LPS)

Beta-lactamase inhibition
 Mechanism of bacterial resistance
 To overcome
o Modify the beta lactam nucleus to produce stable antibiotic in the presence of the enzyme
o Find substance that can inhibit beta-lactamases
 Addition of beta-lactamase inhibitors (suicide inhibitors)
 Clavulanic acid
  Sulbactam (penicillanic acid sulfone)
 Characteristics of an ideal beta-lactamase inhibitor
o Wide spectrum of activity
o Pharmacologically match closely the antibiotic partner
o Enzyme inactivation is irreversible
 All are met by clavulanic acid and sulbactam
Beta-lactamase inhibitors
 Clavulanic acid
- Resembles closely especially amoxicillin
- Fermentation product of actinomycete
o Streptomyces clavuligerus
- Reuse of two beta lactam antibiotics
o First: bind with PBPs and injure the bacteria
o Second: typing up the beta-lactamase
o Example
 Clavulanic + amoxicillin and ticarcillin
 Sulbactam
- Irreversible beta-lactamase inhibitors
- Lesser potency than clavulanic acid
- Semi- synthetic
- In combination with ampicillin

Penicillin
CLASSES
Natural penicillns Penicillinase- Broad-Spectrum
resistant penicillins Penicillins
Penicillin G Methicillin Ampicillin
(aqueous, procaine,
benzathine)
Penicillin V Nafcillin Amoxicillin
Phenethicillin Oxacillin Hetacillin
Cloxacillin Carbenicillin
Dicloxacillin Ticarcillin
Piperacillin
Mezlocillin
Azlocillin
Natural penicillin
 The first antibiotic discovered in 1928 by Sir Alexander Fleming
 Some of the original penicillins produced
 Has limited range of activity
 Highly susceptible to beta-lactamases
 Inactivated by gastric acid
 Only effective against gram-positive bacteria
  Able to achieve concentrations in
o Bone
o Bile
o Soft tissues
o Peritoneum
 Do not accumulate in
o Prostate
o Cerebrospinal fluid
o Aqeous humor
 Not effective in treating intracellular infections
 Pharmacokinetics
o Undergo minimal hepatic metabolism (except ampicillin)
o Plasma clearance through renal excretion
 Glomerular filtration
 Tubular secretion
o Actively transported in
 Kidney
 Brain
 Liver
 Penicillin
o Not a good choice for treating staphylococcal infection (Beta-lactamase)
 Useful in treating urinary tract infection
o Eliminated in the urine unchanged
 Also effective against infection in
o Respiratory tract
o Skin

 Benzylpenicillin (penicillin G)
- Most commonly used betalactam for large and small animals
- Administered through parenteral route
- Hydrolysed rapidly in the stomach (X PO)
- Sodium and potassium forms: given through IV
- Procaine penicillin G and benzylpenicillin G
 prolonged plasma concentrations (slow absorption, therefore long-acting)
 Penicillin V (phenocymethyl penicillin)
- Resists degradation by stomach acid
- Not commonly used in small animals
 Penicillin G (aqueous)
- Potassium or sodium penicillin G
- Used when rapid effect and high plasma concentration is desired
 Especially if administered intravenously
 IM route: lower plasma concentration of longer duration
Extended-spectrum penicillin
- Starts with the isolation of penicillin nucleus: 6- amino penicillanic acid
- Advantage of the new structure
• Stability in acid media and improved oral absorption
• Protection against the attack of beta-lactamase producing staphylococci
• Gram- negative activity at low levels
 E. coli, Salmonella, Proteus
• Activity against P. aeruginosa
 Aminopenicillin
o Preparations
 Ampicillin
 have similar activity; wide range of activity
 Absorbed better PO
 More rapid action
 Amoxicillin
 have similar activity; wide range of activity
 Advantages of amoxicillin
o Can be easily made into palatable oral tablet
o Gives to 50 to 100% higher blood levels than ampicillin after oral
administration
o Has a different and much faster bacterial action
o In humans, penetrates some tissues better than ampicillin
(respiratory infection)
 Hetacillin
 Pro-drug
 More stable in gastric acid than the above-mentioned penicillins; best
absorption
 Metabolized into ampicillin and becomes active
 Cephalosporins
o Chemically related to penicillin
o More resistant to action of beta- lactamase
o Wide margin of safety
o Wider spectrum of activity than penicillin
o First synthesized from Cephalosporium acremonium (fungus)
o High cost
o More active against Pasteurella strains
o Less effective against Corynebacterium pyogenes
o “generation” – based on the invitro antibacterial potency and spectrum of activity
o With every generation
 Loss of gram- positive activity
 Increase in gram- negative activity and spectrum
 Increased resistance to beta- lactamase enzymes
 Increase in cost
o Classification:
 First Generation
- Introduced in 1960s and 1970s
- Susceptible to beta lactamase
- Active against most Gram-positive bacteria
- Limited activity against Gram-negative bacteria
- Effective alternative to penicillin against infections in patient with
penicillin allergy
• Staphylococcal
• Non-enterococcal streptococcal
- Formulations
• Oral: cefadroxil, cephalexin, cephradine
• Injectable: cephalexin, cephalothin, cephapirin, cefazolin
- Spectrum:
• Most aerobic gram-positive bacteria except enterococci and
methicillin- resistant Staphylococcus aureus
• Most anaerobic gram- positive and gram- negative bacteria
except Bacteroides fragilis
 • Common aerobic gram- negative enterics
- Cephalothin
- Cephaloridine
- Cephapirin
- Cefazolin
- Cephalexin
- Cefaclor
- Cephradine
- Cefadroxil
Clinical/Therapeutic Uses
- Surgical prophylaxis (esp cefazolin)
• Vascular
• Orthopedic
• Biliary
• Pelvic
• Intra- abdominal
- Pneumonia (H. Influenza): Cefurozime
- Skin infections: S. Intermedius
- Bovine mastitis
 Second Generation
- Extended activity against specific Gram negative bacteria
- More resistant to beta-lactamase
- Used less frequently in veterinary medicine due to cost
- Spectrum:
• Most aerobic gram- negative bacteria, such as indole positive
Proteus and Bacteroides fragilis
- Cefamandole
- Cefoxitin
- Cefotiam
- Cefuroxime
- Ceforanide
 Third Generation
- Not that effective against Gram bacteria
- Developed for specialized situations
• Burns
• Cancer
• Complicated surgery patients
• For infections resulting from resistant Pseudomonas, Klebsiella
or other highly resistant G- bacteria
- High cost
- Spectrum:
• Some strains of Pseudomonas aeruginosa as well as some
unusual Enterobacteriaciae
• Less active against gram- negative bacteria
- Ceftriaxone
- Ceftizoxime
- Ceftazidime
- Cefsulodin
- Cefotazime
- Cefoperazone
- Cefmenoxime
- Moxalactam
o Pharmacokinetics:
o Resistant to beta-lactamase
o Have good affinity to PBPs of Gram positive bacteria
 o Widely distributed throughout the body
o Penetrate fluids in
 Pleura
 Pericardium
 Synovia
o High levels in urine and bile
o Poor penetration in
 Prostatic tissue
 Ocular humor
 Cerebrospinal fluid
o Less pain is produced during IM injection
o Distribution limited to the extracellular space
o Good for bone infections, e.g. Osteomyelitis
o Cephalothin: drug of choice for measuring susceptibility for all first-generation
agents

New balactams
- Preparations
 Monobactams
o Bicyclic structure is absent, instead monocyclic ring
 Carbapenems
o Have carbon instead of sulfur on the five-
membered ring attached to the beta
lactam ring
o Example:
 Imipenem
 Meropenem
 Ertapenem

TETRACYCLINES
- Group of four-ringed amphoteric compounds that
differ by specific chemical substitutions at different
points on the rings
- Isolated from Streptomyces in late 1940s and early
1950s
- Fluoresce when exposed to ultraviolet light
- Acidic, hygroscopic compounds in aqueous solutions
and easily forms salts with acids and bases
(hydrochloride for oxytetracycline)
- Form insoluble chelates with cations
- They accumulate in growing teeth and bones
- Antimicrobial spectrum includes both gram+ and gram- aerobes and anaerobes,
Rickettsiae, Spirochetes, Chlamydiae, Mycoplasma and some protozoans such as
Anaplasma spp. and Haemobartonella spp.
 - Used for wide variety of diseases
- Abscesses, enteritis, leptospirosis, pneumonia, bovine and swine respiratory diseases,
pododermatitis, treatment of tick-borne pathogen skin and soft tissue infections and uterine
infections.
- Drug Names
 Tetracycline
 Chlortetracycline
 Oxytetracycline
 Doxycycline
 Minocycline
 Tigecycline (Human research)

Mode of Action
- Bacteriostatic & broad spectrum
- Reversibly binds to the 30S ribosomal subunit of susceptible organisms
- After binding to 30S ribosomal subunit, it interferes with the binding of aminoacyl-tRNA to
the messenger RNA molecule/ribosomes complex, thereby interfering with bacterial protein
synthesis in growing or multiplying organisms.

Bacterial Resistance
- Energy dependent efflux
- Altered target (ribosomes are being protected)
- Attack by enzymes liberated by bacteria
- Resistant gene maybe carried by plasmids or
transposons
Pharmacokinetics
- Administration
  Can be given via intravenous route for most tetracyclines or intramuscularly for
oxytetracycline (excipients)
 Doxycycline is well absorbed orally but the rest is poorly absorbed
 Poor orally because they are ionized at gastrointestinal tract
 Reduced drastically by presence of food (except doxycycline)
 Easily chelates to polyvalent cations which decreases absorption several fold.
 Orally or IV every 8-12 hours
 IM injections produce pain, irritation and sterile abscesses (special buffered solutions)
 Oral therapeutic doses should be avoided in adult ruminants and used with caution in
horses
 danger of disrupting ruminal or colonic microflora
- Oral Absorption
 Decreased with co-administration of food, dairy products, polyvalent cations (Ca, Mg,
Fe, Al), kaolin/pectin preparations, iron containing supplements and antacids.
 Avoid co-administration 3 hours before and after meal
- Distribution
 Once absorbed, bind to plasma proteins and distributed to the rest of the body except
for the CNS (lipophilic)
 Doxycycline and minocycline can penetrate the CNS, eye and prostate at therapeutic
concentrations
- Metabolism
 Minimal metabolism except for minocycline (extensive liver)
- Excretion
 Renal by glomerular filtration but small amounts are excreted into feces via bile and/or
diffusion from the blood into the intestine.
 Doxycycline-intestinal excretion is major route of excretion
- Biotransformation
 Plasma half-life is 6-12 hours
DRUG HALF LIFE POINTS TO CONSIDER
Tetracycline 6-11 Shorter in dogs
Oxytetracycline 6-11 Shorter in dogs
Doxycycline 11-23
Minocycline 11-23 Shorter in dogs

Withdrawal Period
 FARAD (food animal residue avoidance databank) recommends:
 Cattle- 28 days for intrauterine treatment (milk testing)
 Sheep- 28 days after IM and SC oxytetracycline administration
o 98 hours for milk withdrawal
 Swine- 14 days following administration of tetracycline product in feed and water
Adverse Side Effects
 All except doxycycline and minocycline are potentially nephrotoxic
 Permanent staining of unerupted teeth (tetracycline-calcium phosphate complex) in
enamel and dentine
 Suprainfections of fungi, yeast or resistant bacteria may occur in GI tract (cats)
 Oral tetracyclines should not be used with herbivores because of serious effects on
ruminant digestion.
 Anti-anabolic effect are seen in large doses because of binding to mitochondrial
ribosomes (elevated BUN) in pre-existing renal disease
  Photosensitivity and hepatotoxicity (rare side effects)
Commonly used Tetracyclines
 Tetracycline
o Available in market as:
 Panmycin
 Duramycin powder
 Chlortetracycline
o First to be discovered and introduced for clinical use in 1948
o Not used in significant degree to small animals for treatment of disease but as feed
and water additives for food producing animals
o Available in the market as:
 Anaplasmosis block
 Aureomycin soluble powder
 Aureomycin tablets
 Aureomycin soluble calf oblets
 Calf scour bolus
 Fermycin
 Doxycycline
o Available in two forms:
 hyclate (common)
 monohydrate
o Available in market as:
 Vibramycin
 Monodox
 Doxy caps
 Minocycline
o Has more activity against penicillinase-resistant stains of S. aureus
o Increases concentration within cell results in an overall increase in pharmacologic
activity (primary advantage)
o Available in market as:
 Minocin
 Oxytetracycline
o Available in market as:
 Biomycin
 Oxybiotic
 Oxy-Tet
 Terramycin
 Terramycin scour tablets
o Available in market as:
 Liquamycin-LA 200
 Biomycin 200
Other Uses
 Immunomodulating drugs
o Inhibition of inflammatory cell infiltration
 Anti-inflammatory drugs
o Affect COX-2 mediated Pge-2 synthesis during inflammation
 In combination with niacinamide it is used as treatment of dogs with:
o 1. discoid lupus erythematosus (DLE)
 o 2.phemphigus foliaceus (PF)
o 3.ulcerative dermatosis in Collies and Shetland Sheepdogs

Clinical dosages used for tetracyclines in animals – Most frequently cited on product labels or in
reputable references based on a consensus of the literature
DRUG SPECIES DOSE
Doxycycline Dogs and cats 5 mg/kg q12h oral
Doxycycline Horses 10-20 mg/kg q12h oral (never IV)
Oxytetracyclin Calves, cattle 22 mg/kg q24h added to drinking water or in feed
e and Pigs
Oxytetracyclin Calves, cattle 6.6-11 mg/kg q24h IM
e
Oxytetracyclin Calves, cattle 20 mg/lkg q24h IM/SC (off label as high as 40 mg/kg)
e
Oxytetracyclin Pigs 6.6-11 mg/kg q24h IM Doses as high as 20 mg/kg IM q24h
e are also used
Oxytetracyclin Sea turtles 40 mg/kg IM, followed by 20 mg/kg q72h, IM
e
Tetracycline Calves 11 mg/kg q12h PO
HCL

FLUOROQUINOLONES
 Structure consists of
o Carboxyl group
o Fluorine atom
o Piperazine ring attached to a quinoline
ring
o Weak acids
o Lipophilic
 Mechanism of action
o Inhibit DNA gyrase
 DNA gyrase- controls the supercoiling of DNA as replicating strands replicate
 Outcome: degradation of chromosomal DNA at the replicating fork
o Bactericidal
 Pharmacokinetics
o Absorption- Oral: rapid
 1 hour in dogs
o Fate
 Distributed wide + CNS, bone and prostate
 Metabolism: hepatic
o Excretion
 Parent drug and metabolites excreted in urine and bile
o Metabolism
 hepatic
 Spectrum of activity
o Broad
o Anaerobes tend to be resistant
 Administration: PO, IM in dogs only
 Bacterial resistance
o Rare
o If present, due to mutation that resist binding of drug to DNA gyrase
 Extra-label use is prohibited in food animals
 Adverse effects
o Erosion of articular cartilage in young dogs
o Do not administer
 Small to medium breeds for the first 8 months of life
 Large breeds: first 18 months of life

 Enrofloxacin
 o Infections
 Dermal
 Respiratory
 Urinary tract
o Half-life
 3-5 hours in dog
 6 hours in cats and horses
 Danofloxacin
o Treatment of bovine respiratory infections including Mannheimia species
 Difloxacin
o Treatment of dermal, respiratory, and urinary tract infections in dogs.
 Orbifloxacin
o Treatment of dermal, respiratory, and urinary tract infections in dogs and cats.
o Half-life
 6 hours in dogs and cats and 9 hours in horses
 Marbofloxacin
o Treatment of dermal, respiratory, and urinary tract infections in dogs and cats.
o Half-life
 9-12 hours in dogs and cats
 Dirofloxacin
o Half-life
 9-12 hours in dogs and cats

AMINOGLYCOSIDES
 Chemistry
o Consist of two or three sugars joined to a hexose (aminocyclitol) by glycosidic bonds
o Polar and basic (amino groups)
o Water soluble sulfate salts
 Mechanism of action
o Bind to 30s ribosomal fragment
o Inhibit protein synthesis and fidelity of messenger RNA (mRNA) translation 
synthesis of abnormal protein
o Uptake by bacteria is dependent on energy (oxygen linked)
o Inhibited by
 Anaerobic and acidic environment
 Calcium and magnesium ions
o Bactericidal (Gram negative aerobes)
o Synergistic to Beta lactams against may Gram positive pathogens
 Therapeutic Uses
 Administration
o IM or SC
o Pulse therapy (high dose once daily) in systemic infection
 Allow full clearance to reduce renal and cochlear toxicity
o For enteric infection, oral dose twice a day
 Absorption
o not absorbed from the gastrointestinal tract
 Distribution
o Extracellular fluid and transcellular fluids (pleural and peritoneal fluids)
o Limited penetration of the CNS or ocular tissue
o Accumulate in the renal cortex and otic endolymph (toxicity)
 Excretion
o Unchanged in the urine by glomerular filtration
o Half-life: 1-3 hrs in most species
 Bacterial Resistance
o Plasmid- mediated
o Quickly developed
o Inactivation by bacterial enzymes: most common
 Amikacin: more resistant to enzymatic degradation
 Adverse Side Effects
o More toxic than other antimicrobials
o Toxicity is reversible: if administration is stopped earlier
o Should not be used with ototoxic drugs
o Ototoxicity: progressive damage to cochlear sensory cells (deafness), vestibular
cells (ataxia) or both
o Nephrotoxicity: damage to membranes of proximal tubular cells:
 Loss of brush border enzymes
 Impaired absorption
 Proteinuria
 Decreased glomerular filtration rate
o Neuromuscular blockade
 Rare
 Prejunctional blockade of ACh release
 Decreased presynaptic sensitivity to ACh
 Muscle paralysis and apnea: Tx- calcium gluconate
  Preparations, Indications, and Antagonistic Drugs
DRUG INDICATION ANTAGONIST COMMENTS
All aminoglycosides Infections caused by Dimenhydrinate and Monitor patients with
susceptible ethacrynic acid affect hearing loss
pathogens, hearing loss;
pneumonias, urinary Do not administer with
tract infections, Methoxyflurane methoxyflurane
endometritis, and
septicemias that are Chloramphenicol
resistant to other
antibiotics
Kanamycin, Kanamycin: not Neuromuscular Administer with
tobramycin, effective against blocking agents calcium and
gentamicin, neomycin, Pseudomonas spp antcholinergic agents
streptomycin as prescribed

Gentamicin Amphotericin B and Monitor renal function

cephalosporins test results frequently
produce when combining these
nephrotoxicity agents

Neomycin For enteric infections; Digitalis glycosides, Dosages may need to

Topical- ear, skin, eye Penicillin V be adjusted when
infection combining these
agents

Gentamicin, Tobramycin: more Carbenicillin, Never mix these two

tobramycin potent ticarcillin, azlocillin, types of antibiotics; if
antipseudomonal mezlocillin, piperacillin a patient is receiving
activity combined therapy,
administer the doses
at least 1 hour apart

 Streptomycin and Dihydrostreptomycin

o Oldest members of aminoglycosides
 Neomycin
o Used orally for treatment of enteric infections
o Topically for skin, ear, and eye infections
 Gentamicin and Amikacin
o Expanded spectrum aminoglycosides (Pseudomonas, Proteus, Staphylococcus
and Corynebacterium spp. as well as gram(-) aerobes.
o Used in all species for the treatment of susceptible infections of the skin,
respiratory tract, ear, eye, urinary tract, and septicemia.
 Tobramycin
o Similar to gentamicin but has more potent antipseudomonal activity and reduced
nephrotoxicity
 Kanamycin
o Similar to gentamicin but not effective against Pseudomonas spp.
o Used in Vet med only as oral preparation combined with Bismuth subcarbonate
and aluminum magnesium sulfate (bacterial enteritis in dogs and symptomatic
relief of associated diarrhea)
AMINOCYCLITOLS
 Spectinomycin & Apramycin
o Chemically similar to aminoglycosides
o Bacteriostatic
o Binds to 30s ribosome and inhibit protein synthesis
 Pharmacokinetics
o similar to aminoglycosides
 Spectrum of activity: effective against
o Gram- negative aerobes
o Mycoplasma spp
 Bacterial Resistance (rare)
o Plasmid- mediated
 Production of enzymes
 Adverse effects
o No significant toxicity
 Preparations and therapeutic uses
 Spectinomycin: for enteric and respiratory diseases
 Apramycin (swine and calves): enteric diseases such as colibacillosis

SULFONAMIDES AND POTENTIATED SULFONAMIDES

- Sulfa drugs
- Derivatives of p- aminobenzene sulfonic
acid
- Structurally similar to p- aminobenzoic acid
(PABA)
o Intermediate in the bacterial
synthesis of folic acid
- Poorly water-soluble unless prepared as
sodium salts
- Structural derivatives differ in R group
component
 Mode of Action
 - Inhibit dihydropteroate synthesis
o Enzyme that catalyzes the incorporation of PABA into dihydrofolic acid
 Folic acid is required for purine and DNA synthesis
 Combinations
- To potentiate its spectrum of activity sulfas are added with trimethoprim
- Trimethoprim act on dihydrofolate reductase
 Bacterial Susceptibility
- Broad Gram positive, Gram negative, and protozoal organisms
- Combination to trimethoprim or ormetoprim (diaminopyrimidines)
 Pharmacokinetics – has independent solubility
o Absorption – well absorbed orally and parenterally
o Distribution
- Widely distributed to tissues
- High plasma concentration
o Metabolism
- Acetylation of the NH2 group
- More extensive and fast in herbivores than carnivores
o Excretion
- Excreted primarily in the kidneys via GF
- low urine pH encourage tubular reabsorption
- Minimally excreted via tears, feces, bile milk and sweat
 Routes of Administration
o IV
o PO
o SC
o IA (barrows, gilts, and boars)
 Therapeutic Uses
PREPARATION SPECIES INDICATIONS REMARKS
Sulfamethazine Cattle Control of respiratory Slowly excreted
(Sulfadimidine) Sheep and GI infections
Swine Promote growth in Plasma levels are
swine maintained for 24 hrs
with one singledose

Follicular cell
hyperplasia of the
thyroid gland (very
high amounts)
Sulfadimethoxine All species Systemic and soft More soluble and less
tissue infections toxic than
sulfamethazine
Coccidiosis
Sulfathiazole Swine Respiratory and Rapidly excreted
Poultry enteric diseases
Given as feed or
Acute infections in water additive
food-producing
Animals (+
sulfathiazole,
sulfamethazine,
sulfapyridine)
Sulfachlorpyridazine Cattle Respiratory and Rapidly absorbed and
Swine enteric infection excreted
(colibacillosis)
Sulfisoxazole and Small animals Urinary tract infection Rapidly secreted and
sulfamethoxazole very soluble

High concentrations
attained with minimal
danger of renal
crystalluria
Sulfacetamide Ophthalmic infection The only sulfonamide
that can be prepared
as sodium salt at
neutral pH
Sulfasalazine Dogs Enteric diseases Cleaved into
Cats (colitis and sulfapyridine and 5-
inflammatory bowel aminosalicylic acid
disease) (5-ASA): bacterial
and anti-inflammatory
actions
Potentiated All species In combination with
sulfonamides trimethoprim or
• Sulfadiazine ormethoprim
trimethoprim
• Sulfamethoxazol
e
trimethoprim
• Sulfamethoxine
trimetoprim
 Dosage Forms
o Solution
o Tablets
o Boluses
o Suspension
 Bacterial Resistance
o Bacteria that is resistant to one sulfonamide is resistant to all.
o Mechanism:
- Increase PABA production
- Decrease affinity of sulfonamide for dihydropteroate synthetase
- Bacterial metabolism of the drug
 Adverse Side Effects
o Urticaria (hives
o Vomiting
o Diarrhea
o Anorexia
o Fever
o Crystal formation (kidneys) which could result to hematuria, proteinuria, and renal
tubular damage
o Keratoconjunctivitis sicca (dogs)
o Limited use for food producing animals
 Withdrawal Period
o 10-15 days for meat, milk, and egg producing animals
MACROLIDES
 Chemistry
o Basic
o Lipid-soluble compounds
 Deoxy sugar + lactone ring
o Prepared as sulfate salts or esterified salts of
 Stearate
 Tartrate
 Estolate
 Lactobionate
 Mechanism of Action
o Inhibit bacterial protein synthesis
 Binding at 50s ribosome
 Prevents translocation of amino acids to the growing peptide chain
o Bacteriostatic
 Pharmacokinetics
o Absorption
 Destroyed by gastric acids
 Good oral absorption (since gastric acids can be stopped) in combination with
distemper
 Enteric-coated preparations
 Prepared as Esterified salts
o Fate
 Widely distributed to all tissues except for CNS
 Tilmicosin higher concentration in lung tissue: 60x higher than serum levels
o Excretion
 Metabolized in the liver, excreted in the bile
 Unchanged in the urine: tilmicosin & tylosin
 Spectrum of Activity (effective against)
o Gram positive aerobes and anaerobes
o Mycopplasma spp
 Therapeutic uses
 Erythromycin
 Alternative to penicillin: Gram positive aerobes and anaerobes = dogs, cats,
and horses
 Drug of choice for:
 Enteritis caused by Campylobacter jejuni in dogs and foals
 Rhodococcus equi - causative agent for pneumonia in foals
 Tylosin
 Cattle, sheep, and swine
 Local and systemic infection
o Mycoplasma
o Gram positive bacteria
o Some gram negative pathogens
 Growth promoter or sometimes feed additive
 Dogs and cats
 Chronic colitis
 Tilmicosin
  Cattle
 Treatment of respiratory disease (caused by Pasteurella spp.)
 Administration
 Erythromycin – dogs, cats, foals
 PO
 IM
 Tylosin – swine, calves, lambs, dogs and cats
 IM
 PO
 Tilmicosin – cattle
 SC
 Bacterial resistance
o Chromosomal or plasmid-mediated
o Effect: decreased binding of drug to 50s ribosome (so ineffective)
 Adverse side effects
 Erythromycin & Tylosin
o Mild gastrointestinal upset (PO)
o Pain & irritation at IM injection site
o Edema of rectal mucosa with mild anal prolapse (swine)
o Severe diarrhea
 Erythromycin – PO in adult ruminants
 Tylosin – PO / parenteral – adult horses
 Since these animals rely on bacterial fermentation in their diet and
has the possibility of killing good bacteria leading to severe diarrhea
 Tilmicosin
o Cardiovascular toxicity (all animals except in cattle)

CHLORAMPHENICOL
 Chemistry
o From Streptomyces venezuelae
o Now produced synthetically
o With dichloracetate and nitrobenzene in the structure
o With Palmitate salts: to become water-soluble and given PO
o Chloramphenicol sodium succinate: water-soluble for parenteral administration
 Mechanism of Action
o Bacteriostatic
o Binds to 50s ribosome
 Inhibit peptide bond formation; thus, inhibit protein synthesis
 Pharmacokinetics
o Absorption
 Faster reabsorption in the GIT
o Fate
 Distribution: well-distributed throughout the body (+CNS (BBB) and eye)
 Metabolism
 Via glucuronide conjugation in the liver
 75% of dose – cats; 90% in dogs
o Excretion
 Half-life
 1-1.5 hours in dogs and horses
 4-5 hours in cats
  Spectrum of activity (effective against)
o Broad spectrum – Gram positive and Gram linconegative bacteria
o Most anaerobic bacteria
 Therapeutic uses
o Species – dogs, cats, horses, birds
o Local infection
o Systemic infection
 Respiratory, CNS, Ocular infection
o Infection caused by
 Anaerobes
 Salmonella spp
 Administration
o Per os
 Every 6-8 hours
 Dogs, birds, horses
 Every 12 hours
 Cats
 Bacterial resistance
o Bacteria produce acetyltransferase (in liver) and other metabolizing enzymes
 Adverse effects
o Anemia
 Dose-related anemia
 Animals and humans
 Inhibit the uptake of iron by erythrocytes
 Slow maturation rate of RBC in bone marrows
 Non-dose-related anemia
 In humans
 Aplastic anemia that is often fatal-residue-induced
 Thus, banned in food-producing animals
o Anorexia and diarrhea-prolonged or high doses; in cats
o Should be used with caution
 Animals with hepatic or renal function impairment since it may exacerbate the
situation
 Neonatal animals since chloramphenicol induces anemia
 kittens
 Not for dogs for breeding purposes (some manufacturer)
 Dogs will have aplastic anemia – deprivation of oxygen – abortion –
dogs will lack nutrient – anomaly
FLORFENICOL
 Fluorinated analog of thiamphenicol
 Same MOA with chloramphenicol
 Approved for cattle use (in USA) to treat Bovine respiratory disease caused by P.
hemolytica, P. multocida and H. somnus

LINCOSAMIDES
 Chemistry
- Derivatives of sulfur-containing octose with amino acid-like side chain
 Preparations
- As hydrochloride or phosphate salts (water-soluble)
- Palmitate salts

 Lincomycin
o From streptomyces lincolnensis
 Clindamycin
 Pirlimycin
 Mechanism of Action
- Bacteriostatic
- Binds to 50s ribosome
 Inhibit protein synthesis
- Should not be combined with antibiotics with the same binding site (overlapping action –
antagonistic effect)
 Chloramphenicol
 Macrolides
 Pharmacokinetics
- Absorption
 50% for lincomycin
 90% for clindamycin
- Fate
 Distribution
 Wide
 Good in bone and soft tissues
 High CNS levels if meninges are inflamed because of vasodilation (BBB is a tuft of
capillaries na mu inflammation)
 Metabolism: liver
 60% lincomycin
 90% clindamycin
 Excretion: urine, bile feces
 Unchanged
 Metabolites
 Spectrum of activity (effective against)
- Gram positive aerobes and anaerobes
 Toxoplasma spp
 Mycoplasma spp
 Against anaerobes: Clindamycin > lincomycin
 Therapeutic uses
 Lincomycin
 administered IM or added to drinking water
 Swine (also for dogs, cats, chickens)
 Control and treatment of
 Swine dysentery
 Infections caused by
 Staphylococcal
 Streptococcal
 Mycoplasmal infection
 Clindamycin
 Administered PO or IM
 Dogs and cat
 Periodontal disease
  Osteomyelitis
 Dermatitis
 Deep soft tissue infections caused by Gram positive organisms
 Toxoplasmosis
 Pirlimycin (mastitis tubes)
 Clinical and subclinical mastitis in dairy cattle
 Bacterial resistance
- Altered drug binding
- Cross-resistance between lincosamides and macrolides (! Consider mechanism of action)
 Adverse effects
- Horses, rabbits, hamster, guinea pigs (gut fermenters)
 Severe, often fatal diarrhea = altered GI flora
- Dogs, cats, swine
 Rare
 Neuromuscular blockade
 High doses
 Combined with anesthetics

MISCELLANEOUS ANTIBIOTICS
 Bacitracin
o Produced from Bacillus subtilis
 Discovered from a contaminated wound of a patient named Margaret Tracy in
early 1940s (B. licheniformis)
o Freely soluble in water (polar and insoluble to lipid loving
o Insoluble in acetone, chloroform, and ether
 Mechanism of Action
o Inhibits second step of cell wall synthesis
 Inhibits peptidoglycan synthesis by nonspecifically blocking phosphorylase
reactions
o Bactericidal
 Pharmacokinetics
o Not absorbed orally (poorly absorbed)
o Effects after systemic administration
 Careful since it can cause nephrotoxicity, pain, induration, petechiae at
site of injection
o Combined with other antibiotics to enhance effectivity
 Zinc bacitracin – increases activity of bacitracin due to astringen effect
(decrease inflammation) of zinc
 +polymyxin B/neomycin – widens the spectrum
 Spectrum of activity (effective against)
o Gram positive bacteria (topical and parenteral administration)
o Spirochetes
 Therapeutic uses
o Topical infections – skin, ear, and eye
 In combination of neomycin and or polymyxin B
 Prevent and treat clostridial enteritis
o Added to feeds in swine
 Prevent and treat clostridial enteritis
 Promote growth (advantage)
 Vancomycin
 Mechanism of Action
o Blocks the second stage of bacterial cell wall synthesis
 Inhibit polymerase release from the cell membrane
o Bactericidal
 Pharmacokinetics
o Not absorbed orally
o Distributed to ECF and transcellular fluid
o Excreted unchanged by glomerular filtration
 Spectrum of activity (effective against)
o Gram positive bacteria
 Therapeutic use
o Reserve antibiotic (IV) for methicillin-resistant staphylococcal infections of bone
and soft tissue in dogs and cats
o Topical
 Treat Gram negative infections of skin, eye, and ear in all species
 Combined with bacitracin to have broad spectrum effect
o Oral (cattle and swine)
 Treatment of gram negative enteric infections
 Adverse side effects
o Associated with large doses or prolonged administration
 Ototoxicity
 Nephrotoxicity
o Systemic toxicity if administered parenterally

 Polymyxin B
 Mechanism of Action
o Interacts with phospholipids in the bacterial cell membrane which result in
 Detergent-like effect
 Membrane disruption
o Bactericidal for Gram negative bacteria
 Pharmacokinetics
o Not absorbed orally
o Too nephrotoxic for systemic use

 Metronidazole
 Chemistry
o Nitroimidazoles include:
 Metronidazole
 Ipronidazole
 Dimetridazole
 ronidazole.
o heterocyclic compounds containing a fivemembered ring similar to the
nitrofurans.
o Only metronidazole is used in veterinary medicine.
 Mechanism of action
o Metronidazole is taken up by anaerobic bacteria and protozoa and reduced to a
cytotoxic metabolite, which disrupts DNA
o bactericidal against most obligate anaerobes
o active against protozoa
  Giardia & Trichomonas spp.
 Therapeutic uses
o Nitroimidazoles
 demonstrated carcinogenicity in laboratory animals
 use is banned in food-producing animals.
o Metronidazolevis
 used in dogs, cats, and horses
 for the treatment of severe infections caused by anaerobic pathogens,
especially brain abscesses and pelvic, genitourinary tract, and respiratory
infections
o Metronidazole
 used to treat protozoal infections
 giardiasis and trichomoniasis in dogs and cats
 Pharmacokinetics
o well absorbed orally and widely distributed, including the CNS
o Hepatic metabolism by oxidation and conjugation occurs for one-third to one-half
of administered drug
o excreted in urine and feces
o The elimination t 1/2 in dogs and horses are 3–5 hours.
 Adverse effects. High or prolonged dosage may produce neurotoxicity with signs that
include nystagmus, ataxia, and seizures.
 Pharmacokinetics
o Absorption
 Bioavailability (PO): 50-100%
 Absorption is enhanced with food (increased bile secretion)
 Blood level (peak) is achieved 1 hour after administration
o Distribution
 Rapidly and widely distributed: lipid- soluble
o Metabolism and excretion
 Hydroxylation and conjugation (Liver)
 Excretion of metabolites and unchanged drug: feces and urine
 Therapeutic uses
o Giardiasis
o Histomoniasis
o Babesiosis
o Trichomoniasis
o Amebiasis
 Toxicity
o Lethargy
o Weakness
o Ataxia
o Rigidity
o Anorexia
o Vomiting
o Diarrhea
o Reversible leukopenia
o Hepatoxicity

 Rifampin
 Mechanism of action
 o inhibits DNA-dependent RNA polymerase, which prevents initiation of RNA
synthesis
o bactericidal for mycobacteria and Gram positive pathogens
o effective against intracellular infections.
 Therapeutic uses
o combined with erythromycin in the treatment of R. equi infections in foals
o used in combination with other antifungal agents to treat fungal infections
 aspergillosis or histoplasmosis in dogs and cats when infection involves
the CNS
 Pharmacokinetics
o absorbed orally and rapidly distributed to cells and tissues
o metabolized in the liver to a deacetylated form that also has antibacterial activity
o Both this metabolite and parent drug are excreted primarily in the bile, but up to
30% may be excreted in the urine
o Parent drug is substantially reabsorbed in the gut, but the metabolite is not.
o Reported elimination t 1/2 for various species
 6–8 hours in horses
 8 hours in dogs
 3–5 hours in sheep
 can induce hepatic microsomal enzymes, elimination rates may increase
with repeated doses.
 Administration.
o orally three times a day in foals, dogs, and cats.
 Adverse effects.
o Side effects are rare.
o Hepatotoxicity may occur in animals with preexisting liver disease
o Rifampin may produce red-orange colored urine, sweat, and saliva but this is not
harmful.

 Tiamulin
 Binds to 50s ribosome, inhibit protein synthesis
 Spectrum of activity is similar to tylosin
– Gram- positive cocci
– Mycoplasmae
– Spirochetes
– Gram- negative: Haemophilus spp
 Well- absorbed orally
 Metabolized in the liver
 eliminated via
o Feces (70%)
o Urine (30%)
 Therapeutic use
o Swine
 Haemophilus pneumonia
 Swine dysentery
 Adverse effects
o Metabolites from urine may cause dermatitis in overcrowded pigs
 With erythema
 prutitus
 Nitrofurans
  Mechanism of action
o reduced by bacteria to reactive intermediates that inhibit nucleic acid synthesis
o produce DNA fragmentation and may also block mRNA translation
o broad spectrum and bacteriostatic.
 Therapeutic uses
o occasionally used in the treatment of lower urinary tract infections in dogs and
cats
o administered orally every 6–8 hours and is most effective in acid urine.
o Nitrofurazone used topically as an antibacterial ointment, powder, and water-
soluble wound dressings in all species.
 Pharmacokinetics
o Nitrofurantoin
 absorbed orally
 rapidly excreted by glomerular filtration and active secretion.
 Peak urine levels are achieved less than 1 hour after administration
 Plasma t 1/2 is 20 minutes in humans; no information for animals.
 Adverse effects.
Side effects are rare. Nausea, vomiting, and diarrhea may occur in dogs and cats
following oral administration. Nitrofurans may not be used in food-producing animals
(include topically) because they have been shown to be potential carcinogens in
laboratory animals.

 Novobiocin
 coumarin antibiotic
 acidic
 Mechanism of action
o blocks binding of ATP to DNA gyrase to inhibit supercoiling of bacterial DNA
o bacteriostatic for Gram positive cocci, especially S. aureus.
 Therapeutic uses
o used for wound treatment
o treatment of mastitis particularly Staphylococcus infections
o less potent against Streptococcus infections.
 Pharmacokinetics
o absorbed orally with peak levels in 2–4 hours
o Tissue penetration is relatively poor
o excreted primarily into bile and feces
o Plasma t 1/2 after oral administration in humans is ∼6 hours; no information is
available for animals.
 Administration
o given by intramammary infusion usually combined with procaine penicillin to limit
the development of resistance
o combined with tetracycline in a proprietary preparation (AlbaPlex®) for oral
administration twice a day in dogs for susceptible infections.
 Adverse effects
o Novobiocin does not produce systemic toxicity when administered topically or
orally

 Streptogramins
 Chemistry
o Virginiamycin used for poultry
 o mixture of
 streptogramin B, a macrolide (virginiamycin M)
 streptogramin A, a cyclic hexadepsipeptide (virginiamycin S)
o The human preparation Synercid R is a mixture of the macrolide, dalfopristin,
and the cyclic hexadepsipeptide, quinupristin.
 Mechanism of action
o bind to the 50S ribosome to inhibit protein synthesis
o Virginiamycin is bactericidal against Gram positive aerobic and anaerobic
bacteria.
 Therapeutic uses
o Virginiamycin is administered as:
 medicated feed additive in broiler chickens
 swine as a growth promotant
 prevention of necrotic enteritis in broiler chickens
 control of swine dysentery in pigs weighing up to 120 lbs
 feed additive in cattle to increase feed efficiency
 to reduce the incidence of liver abscesses.
o Synercid R is used in humans for treatment of:
 vancomycin-resistant enterococcal infection
 methicillin-resistant S. aureus.
o Use of virginiamycin in poultry
 may lead to transferable resistance to humans and limit the value of
Synercid R .
 Pharmacokinetics
o administered orally
o Since it is not absorbed, its antibacterial effects are limited to the GI tract.

 Ionophore antibiotics
 Chemistry
o polyether antibiotics derived from Streptomyces
o used primarily in poultry and swine for feed efficiency and anticoccidial activity
o Includes monensin, lasalocid, laidlomycin, salinomycin, and narasin.
 Mechanism of action
o act as alkali metal ionophores
o They complex with Na+ in the cell membrane to produce
 passive extracellular transport of K+
 intracellular influx of H+
 killing bacteria and coccidian by lowering intracellular pH.
o In the rumen,
 ionophores selectively affect Gram positive organisms resulting in a shift to
Gram negative populations in the rumen microflora
 increases the production of propionic acid
 decreases the production of acetic and butyric acids by rumen bacteria
 This change in volatile acids (VFA) increases feed efficiency by reducing
bacterial energy losses to CO2 and methane, thereby increasing the
energy content per unit of feed.
 Therapeutic uses
o administered as premixes or medicated feed for growth promotion, feed
efficiency, and control of coccidiosis in cattle and broiler chickens
 Monensin
  Lasalocid
 laidlomycin
o administered as medicated feed to broiler chickens for prevention of coccidiosis
 Salinomycin & narasin
 Pharmacokinetics
o absorbed orally.
o Monensin
 absorption is 50% in ruminants
 rapidly and extensively metabolized by the liver
 excreted by bile and eliminated in the feces.
o Absorption more complete
o metabolism is slower in monogastric animals (especially horses who has greater
toxicity)
 Adverse effects
o Toxicity of ionophores when used in species for which they are approved is
uncommon, unless mixing errors occur.
o Ionophore toxicity is due to:
 cellular electrolyte imbalances,
 increased extracellular K+, intracellular Na+ and Ca2+ concentrations =
resulting in cellular damage and death
 The increased intracellular Ca2+ concentration is due to the exchange of
Na+ for Ca2+ by Na+–Ca2+ exchanger; this exchange is particularly
prominent in cardiac and skeletal muscles and these are usually the most
severely affected.
o Horses are the most susceptible species to toxic effects when accidentally
exposed to ionophore containing feeds.

Antifungal agents p. 365 - Hsu