Antimicrobials

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Antimicrobials

• CHAPTER 10-1
• Dr. Dipa Brahmbhatt VMD MpH
• dbrahmbhatt_at_vettechinstitute.edu

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Objectives

• Mechanisms of action of antibiotics
• Adverse drug reactions and how to mitigate these
• Selection of antibiotics Ab resistance, drug
  absorption, distribution, location of bacteria
  and drug elimination
• Antifungal drugs Advantages, Disadvantages and
  side effects

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Basic Terminology

• An antimicrobial is a chemical substance that has
  the capacity, in diluted solutions
• To kill (biocidal activity) OR
• E.g. bactericidal effective in immunocompromised
  patients
• Cephalosporins, Penicillin family,
  Aminoglycosides, fluoroquinolones
• Inhibit the growth (biostatic activity) of
  microbes
• Functional immune system
• Sulfonamides, tetracycline, lincosamides/clindamyc
  in. chloramphenicol

Staphylococcus
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Basic Terminology

• Antimicrobials can be classified as
• Antibiotics
• Antifungals
• Antivirals
• Antiprotozoals
• Antiparasitics Ch 12

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Pathogenic Microorganisms

• Cause a wide variety of infections and illness in
  different organs or body systems
• May be classified as local or systemic
• A localized infection may involve skin or an
  internal organ and may progress into a systemic
  infection
• A systemic infection involves the whole animal
  and is more serious than a local infection

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Pathogenic Microorganisms

• Enter the body through
• Integumentary
• Break through skin or mucous
• membrane
• Respiratory system
• Inhaling contaminated droplets
• GI tract
• Ingestion contaminated food and water
• Genitourinary
• Contaminated vaginal secretions, semen or urine

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Antimicrobials

• Prokaryotic
• Fewer organelle smaller than Euk.
• Cell wall
• /- capsule
• Cell/ plasma membrane
• Nucleoid
• Cytoplasm
• Ribosomes
• /- pili, plasmids, flagellum
• Few have endospore

• Eukaryotic
• Cell / plasma membrane
• Nucleus
• Nucleolus
• Cytoplasm
• Mitochondria
• Golgi apparatus
• Endoplasmic reticulum
• Ribosomes
• Vacuoles
• Lysosomes

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No ribosome Syn. Lipids and some carbohydrates
Nucleolus Produces RNA that Forms ribosomes
Energy producers

• Controls cellular activity
• Genetic material

Boundary/ semi-permeable
Small, membrane bound Organelles with food,
water or metabolic waste
Digestive system of the cell
Site of protein synthesis
Semi-fluid medium with organelles
Has ribosomes Syn. proteins
Chemical processor of the cell
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FEW BACTERIA HAVE ABILITY TO PRODUCE
ENDOSPORES Persists in variable environment
Not membrane bound
Hairlike protein extensions Attach/communicate
with Other cells
Smaller than Eukaryotic
Mobility
Barrier against phagocytosis
DNA outside chromosome Replicate
independently Pass info via pilus
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Antibiotics

• Antibiotics work only on bacteria and are
  described by their spectrum of action (range of
  bacteria for which the agent is effective)
• Narrow-spectrum antibiotics work only on either
  gram-positive or gram-negative bacteria (not
  both)
• Broad-spectrum antibiotics work on both
  gram-positive and gram-negative bacteria (but not
  necessarily all)
• Antibiotics can be classified as bactericidal or
  bacteriostatic
• Bactericidals kill the bacteria
• Bacteriostatics inhibit the growth or replication
  of bacteria

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EFFECTIVE ANTIBIOTIC

• Kill/ disable pathogen w/o affecting the host
• Bacteria sensitive to antibiotic
• Animal can tolerate high doses of antibiotic
• Gets into infection site at high enough doses
• Challenging e.g. bacteria in brain (listeria)
  however it is difficult for penicillin to cross
  the blood-brain-barrier
• Drug Selection
• Client compliance
• ease of administration
• convenient dose schedule and form
• cost

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Gram stain Procedure
Staphlylococcus sp. Streptococcus sp.
Salmonella sp. Proteus sp.
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Agar Diffusion Test

• A.k.a. Kirby-Bauer antibiotic sensitivity testing
• Used to determine if a particular antibiotic is
  effective against a particular bacterium.
• Antibiotic-impregnated disks placed onto agar
  plates containing bacteria being tested.
• After incubation at proper temperature for the
  proper time, zones of inhibition (clear zones)
  are measured and compared to a standardized chart
  to determine R.
• R resistant (antibiotic does not work) high
  conc. causes significant SE in host
• I intermediate (antibiotic may work)
• S sensitive (antibiotic will work)

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Broth Dilution Method
Minimum Inhibitory Concentration (MIC) Lowest
conc. Of Antibiotic that visually inhibits
growth of bacteria
High MIC resistant
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Considerations when using antibiotics

• Antibiotic resistance
• Means that the bacteria survive and continue to
  multiply after administration of the antibiotic
• Occurs when bacteria change in some way that
  reduces or eliminates the effectiveness of the
  agent used to cure or prevent the infection
• Causes
• Drug not properly used (used for viral infection)
• Not administered for proper length of time
• Not at proper dose

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Considerations when using antibiotics

• Resistance develops by
• Natural/Intrinsic resistance
• Ab. Acts on enz. Systems or biological processes
• not used by microorganism
• Acquired resistance sensitive before
• Bacterial mutation
• E.g. bacteria produce beta-lactamase, inactivates
  penicillin
• Bacteria acquiring genes that code for resistance
• R (resistance) Plasmids
• Other means
• Cross resistance e.g. between Abs. with same
  actions penicillins cepalosporins
• Noscomial infections (sick patients and close
  contact)
• Handwashing

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Considerations when using antibiotics

• Responsibility
• Administer appropriate dose interval time
  manner
• Client education
• Follow instructions
• Finish medication

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Considerations when using antibiotics

• An antibiotic residue is the presence of a
  chemical or its metabolites in animal tissue or
  food products
• Residue is not usually degraded by cooking/
  pasteurization
• Antibiotic residues can cause allergic reactions
  in people or can produce resistant bacteria that
  can be transferred to people who consume these
  products
• Withdrawal times for antibiotics are aimed at
  eliminating antibiotic residues in food-producing
  animals

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Considerations when using antibiotics

• The FDA approves all drugs marketed for use in
  animals in the United States
• The FDA also establishes tolerances for drug
  residues to insure food safety
• The FDA also establishes withdrawal times and
  withholding periods
• Times after drug treatment when milk and eggs are
  not to be used for food, and also when animals
  are not to be slaughtered for their meat
• FARAD Food Animal Residue Avoidance Databank

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How Do Antibiotics Work?

• Antibiotics work by a variety of mechanisms
• 1) Inhibition of cell wall synthesis
• Bacteria have cell walls animals dont
• Bactericidal growing and dividing not in
  developed
• bacteria
• 2) Damage to the cell membrane
• Alters membrane permeability
• Bactericidal/static
• Loss of cellular substances
• causes lysis of cell

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How Do Antibiotics Work?

• 3) Inhibition of protein synthesis
• In ribosomes
• RNA copy (of DNA), t RNA (AAs)
• Disrupts linkage of AAs
• Bactericidal/static
• 4) Interference with metabolism
• Block enzymes / essential nutrients
• Cant divide and cell death
• Bacteriostatic
• 5) Impairment of nucleic acids
• Intefere with nucleic acid production
• Cant divide/ function properly
• Bactericidal

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• -static/cidal
• Lincosamides
• Macrolides
• Tetracyclines
• Aminoglycocides

• -cidal
• quinolones

• -static
• sulphonamides
• Block enzymes

• -cidal
• Penicillin
• Cephalosporins

• -static/cidal
• Polymyxin B (TAO)

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Classes of Antibiotics

• Cell wall/ membrane agents
• Protein synthesis agents
• Antimetabolites
• Nucleic acid agents
• Miscellaneous agents

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Cell Wall Agents

• Penicillins
• Have beta-lactam structure that interferes with
  bacterial cell wall synthesis
• Suffix cillin
• Spectrum of activity depends on the type of
  penicillin mostly gram
• Effective against actively growing bacteria (cell
  division cell wall)
• Bacteriostatic should not be used/ used
  judiciously at same time as bactericidal drug
• Hydrophilic at blood pH hence difficult to reach
  therapeutic levels eye, brain, prostate
• Excreted as a whole in urine. Hence good for UTI,
  kidney, bladder, genitourinary tract
• Cross resistance resistance to one Ab in group
  than probably to other as well
• Pseudomonas otitis externa is resistant to
  penicillin

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Cell Wall Agents

• Natural Penicillins
• Penicillin G and V are narrow-spectrum
  gram-positive antibiotics (Staphylococcus sp.
  Streptococcous sp.)
• Penicillin G is given parenterally (inactivated
  by stomach acid)
• a) Aqueous solution (only one given IV) Only
  sodium or potassium salt of Pen-G can be admin.
  IV, IM, SQ peak levels 20 mins
• Refrigerated 14 days
• b) Suspension Procaine Benzathine increase
  duration. IM/SQ
• PPG 24 hr. duration
• Benzathine PG 5 days
• Peak plasma not as high as aqueous
• SE Anorexia, V/D (orally), hypersensitivity

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Cell Wall Agents

• Aminopenicillins Penicillin V is given orally
• Give PCN on empty stomach (except amoxicillin)
• Penicillin V potassium preferred better absorbed
  in GI and stable in stomach acid
• Broader-spectrum penicillins are semi-synthetic
• Slowly excreted from kidneys
• Examples include amoxicillin (ok with food),
• Dont give with food ampicillin (POLYFLEX
  SUSPENSION) , carbenicillin, ticarcillin, and
  methicillin
• More gram than Pen G

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Cell Wall Agents

• Beta-lactamase resistant penicillins
• More resistant to beta-lactamase / penicillinase
  (an enzyme produced by some bacteria
  Staphylococcus that destroys the beta-lactam
  structure of penicillin)
• Examples include methicillin, oxacillin,
  dicloxacillin, cloxacillin, and floxacillin
  narrow spectrum against beta lactamase
• Bovine staphylococcal mastitis, staphylococcal
  osteomyelitis, staphylococcal pyoderma,
• Potentiated penicillins are chemically combined
  with another drug to enhance the effects of both
• An example is a drug containing amoxicillin and
  clavulanic acid (from streptomyces) / Augmentin
  (which binds to beta-lactamase to prevent the
  beta-lactam ring from being destroyed)

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Penicillins - Considerations

• Hypersensitivity
• Anaphylactic reactions
• Injectable products
• Aggressive therapy, epinephrine,
• corticosteroids
• Milder skin rashes/ urticaria, swelling LNs,
  eosinophilia/ neutropenia, fever
• Cross-reactivity to other drugs in family
• MAKE NB OF THIS CLEARLY ON RECORD
• Destroy normal flora superinfection/
  suprainfection
• Severe diarrhea and death Guinea pigs, ferrets,
• hamsters and rabbit
• use with caution snakes, birds, turtles,
  chinchillas
• Withdrawal time for milk and meat

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Cell Wall Agents

• Cephalosporins
• Are semi-synthetic, broad-spectrum antibiotics
  that are structurally related to the
  penicillin's, work on rapidly growing bacteria,
  cephalosporinases bacterial beta lactamases
• Have the beta-lactam ring
• ceph- or cef- prefix in the drug name
• Not TOC for brain/ eye/ prostate infections
• High concentration in urine
• Are classified into four generations
• In general, as the number of the generation
  increases, the spectrum of activity broadens (but
  becomes less effective against gram-positive
  bacteria)
• 1st generation cefadroxil (cefa-tabs,
  cefa-drops) cephapirin (cefa-lak and cefa-dri
  intramammary infusions) human products
  cephalexin gtgt gram Staphylococcus,
  Streptococcus
• 2nd generation Human product CEFOXITIN
  (mefoxin)
• 3rd generation ceftiofur (Naxcel/ excenel)
  cefpodoxime (Simplicef) human cefotaxime
  (claforan). Most injectable except for
  cefpodoxime

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• Convenia (cefovecin sodium)
• First antibiotic that provides an assured course
  of treatment by providing up to 14 days of
  treatment in a single injection, eliminating
  missed doses associated with daily oral
  antibiotic administration
• Labeled specifically for secondary superficial
  pyoderma, abscesses, and wounds (S. intermedius,
  S. canis ) in dogs and abscesses and wounds (P.
  multocida) in cats.
• Must be reconstituted, refrigerated, and used
  within 28 days of reconstitution
• Second dose may be necessary in 14 days.

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Cephalosporins - Precautions

• Mostly safe, less hypersensitivity reactions then
  penicillin
• Suprainfection may have with 1st generation
  cephalosporins
• Oral drugs SE anorexia, v/d
• Efficacy reduced with bacteriostatic drugs

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References

• Romich, J.A. Pharmacology for Veterinary
  Technicians, 2nd edition. 2010.
• Bill, R.L. Clinical Pharmacology and Therapeutics
  for the Veterinary Technician, 3rd edition. 2006.