Antimicrobials

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Antimicrobials

• CHAPTER 10-2
• Dr. Dipa Brahmbhatt VMD MpH
• dbrahmbh_at_yahoo.com

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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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Cell Wall Agents

• Bacitracin
• Disrupts the bacterial cell wall and is effective
  against gram-positive bacteria
• Used topically (skin, mucous membranes, eyes) and
  as a feed additive
• Nephrotoxic
• Vancomycin
• Bacteriocidal effective against many
  gram-positive bacteria used for resistant
  infections
• Useful in treatment of Staphylococcus aureus

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Cell Membrane Agents

• Polymyxin B
• Works by attacking the cell membrane of bacteria
  (remember that animal cells have cell membranes
  too)
• Is a narrow-spectrum, gram-positive antibiotic
• Not absorbed when taken orally or applied
  topically
• Used as an ointment or wet dressing
• Often combined with neomycin and bacitracin
  triple ABX ointment

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Protein Synthesis Agents

• Aminoglycosides
• Interfere with the production of protein in
  bacterial cells
• Are a specialized group of antibiotics with a
  broad spectrum of activity, used for
  gram-negative bacteria. Pneumonia
• Aerobic bacteria, bactericidal
• Are not absorbed well from the GI tract, so are
  given parenterally
• Suffix micin or mycin (but are not the only
  group to use these suffixes e.g. clindamycin,
  erthromycin)
• T1/2 2-5 hours still SID for safety
• Penicillin's (cell wall) will enhance their
  activity
• Cross resistance not as common as penicillins

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Protein Synthesis Agents

• Aminoglycosides
• Pharmacokinetics
• Hydrophilic mostly parenterally
• Well absorbed in GI through neonates,
  haemorrhagic,
• necrotic intestine
• Well absorbed locally if skin is denuded/ abraded
• Parenterally gt ECF volume of distribution is
  larger
• in neonates/ young animals gt low drug conc. Most
  diluted in ECF
• Not good for brain/ eye infections systematically
  
• Accumulate bronchioles, kidneys, inner ear,
  cross placenta
• Eliminated in Kidney
• Not effective with cellular debri e.g pus, dirt,
  fecal material, anaerobic conditions deep
  wounds, abscess

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Protein Synthesis Agents

• Aminoglycosides
• Side effects are nephrotoxicity and
• Ototoxicity cats sensitive, vestibular signs
• circling, head tilt, nystagmus
• Increase dosage interval for safety
• Monitor BUN and serum creatine (70-75 kidney
  damage), urine sediment, urine SPG
• Early signs casts or increased protein - urine
• Examples include gentamicin, neomycin, amikacin,
  streptomycin, kanamycin, netilmicin, tobramycin,
  and dihydrostreptomycin
• Dont use in pregnant animals, geriatric
  patients, dehydration, shock or kidney disease
• NOT approved for use in food-producing animals.

Granular casts
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Protein Synthesis Agents

• Tetracyclines (Oral and parenteral forms)
• Are a group of bacteriostatic antibiotics with a
  broad spectrum Ab.
• Rickettsial agents Treats Lyme disease
  (borreliosis), Ehrlichia - dogs, Hemobartonella
  dogs/ cats, RMSF
• Salmon poisoning dogs
• Mycoplasma pneumonia
• Chlamydial infections ocular infections feline
• Psittacosis birds
• Epiphora canine?
• Are recognized by cycline suffix
• Examples include
• Older tetracyclines hydrophilic - tetracycline,
  oxytetracycline
• Newer tetracyclines lipophilic -
  chlortetracycline, doxycycline, and minocycline.
  Longer t1/2, more broad spectrum, better
  penetration

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Protein Synthesis Agents

• Tetracyclines Dont use with penicillins/
  cephalosporins
• Pharmacokinetics
• Doxy/minocycline lipophilic better oral
  absorption
• Only 20 not absorbed with chelators, not
  significant
• Penetrate brain, eye and prostate better than
  older drugs
• Doxycycline uses CNS signs related to Lyme
  disease/ excreted in GI hence ok to use in kidney
  cases. GIVE WITH FOOD
• IV Doxycycline DONT GIVE TO HORSES, cardiac
  arrhythmias, collapse, death
• Oxt/tetracycline hydrophilic. Expired products gt
  FANCONI syndrome (glycosuria)
• Readily chelated (bound and ppt. out of solution)
  by minerals with divalent cations
• Ca , Mg , Fe , Cu
• If given with milk products, antacids (Mg ),
  Fe supplementation, andidiarrheal kaolin/
  pectin, bismuth subsalicylate (Pepto-Bismal)
  chelate drug in GI and drug is not absorbed
• Oxytetracycline IM LA 200 q 2-3 days
• Tetracycline PO SE superinfection, v/d,
  anorexia. Cats tolerate this less fever,
  depression, abdominal pain
• Excreted mostly by kidney than liver
• Young animals chelate Ca yellow, mottled
  teeth also combine with Ca and slow bone
  development

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Protein Synthesis Agents

• Chloramphenicol bacteriostatic
• Is a broad-spectrum antibiotic that penetrates
  tissues and fluids well (including the prostate,
  eyes and CNS) and rickettsiae
• Has toxic side effects (bone marrow depression
  myelosuppression) that extremely limit use
  aplastic anemia human
• In cats kidney function is essential to use this
  drug
• Use caution when handling this product
• Chloramphenicol is the only drug in this category
• Also available in ophthalmic solution
• Banned from use in food-producing animals.
• Dont use in pregnant animals and use with
  caution in neonate kittens
• Concurrent use with phenobarbital and primidone
  will make them toxic in the body
• Not considered a first-line drug

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Protein Synthesis Agents

• Florfenicol (Nuflor) Newer. Bacteriostatic
• Is a synthetic, broad-spectrum antibiotic
• Injectable solution
• Used to treat bovine respiratory disease complex
  (shipping fever)and foot rot.
• 2 injections IM every 48 hrs. apart
• Drug withdrawal 28 days
• Side effects include local tissue reaction
  (possible loss of tissue at slaughter), in
  appetence,
• decreased water consumption, and
• diarrhea
• Florfenicol is the only drug in this
• category
• Dont use in breeding animals

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Protein Synthesis Agents

• Macrolides
• Interfere with the production of protein in
  bacterial cells
• Are broad-spectrum antibiotics that have a large
  molecular structure. Dont penetrate CNS.
• Used to treat penicillin-resistant infections or
  in animals that have allergic reactions to
  penicillins
• May cause stomach upset in animals
• Erythromycin (oral or ointment) In foals
  respiratory disease can get superinfection hence
  add probiotics. Label foal Rhodococcus Equi. In
  adult horses and ruminants (oral) diarrhea
• Tylosin (used mainly in livestock even though
  labeled by dogs/cats - can cause fatal diarrhea
  in horses)
• Tilmicosin (Micotil SQ used to treat bovine
  respiratory disease single injection). Can
  cause death IV and irritating IM. Toxic horses,
  primates, swine, humans (farmers who inject
  themselves accidentally or in the eyes)
• Azithromycin (Human drug Zithromax) Mycoplasma
  - FRDC
• SE Intestinal cramping, abdominal pain,
  diarrhea, suprainfection (erythromycin and
  Azithromycin)

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Protein Synthesis Agents

• Lincosamides -cidal/static
• Interfere with the production of protein in
  bacterial cells
• Are narrow-spectrum, gram-positive aerobic cocci
  antibiotics e.g. Staphylococcus aureus
• Side effects include GI problems
• Veterinarians typically use erythromycin instead.
• Examples
• Clindamycin (Antirobe) Label dogs. Anaerobic
  bacteria, deep pyoderma, abscess, dental
  infections, bite wounds, osteomyelitis
• Pirlimycin (Pirsue) 36 hrs - milk 28 days -
  meat
• Lincomycin Label dogs, cats, swine, poultry
• DONT USE rabbits, hamsters, guinea pigs, horses,
  ruminants
• severe GI effects and also death
• SE v/d and bloody diarrhea
• Nursing kittens/ pups DIARRHEA
• With Kaopectate (antidiarrheal) cannot absorb
  drug hence give lincomycin first than 2 hours
  later antidiarrheal.

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Nucleic Acid Agents

• Fluoroquinolones/ Quinolones -cidal
• Are antibiotics with fluorine bound to the
  quinolone base, which increases the drugs
  potency, spectrum of activity, and absorption
• Disrupt DNA gyrase of bacteria
• Are broad-spectrum antibiotics (gram and gram
  -) Staphylococcus, Pseudomonas (better than
  Gentamicin), Klebsiella, Escheria coli,
  Salmonella spp. DONT use for Streptococcus spp.
  Or anaerobes
• floxacin suffix
• Examples
• Enrofloxacin (Baytril) 1st . Label dog/cat.
  5mg/kg
• Ciprofloxacin Label human.
• Marbofloxacin (Zeniquin). Label dog/cat
• Orbifloxacin (Orbax). Label dog/cat
• Difloxacin (Dicural)
• Sarafloxacin (Saraflox). Label poultry, REMOVED
• Nalidixic acid (older) and norfloxacin (human)
  not often used in vet medicine

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Nucleic Acid Agents

• Fluoroquinolones/ Quinolones -cidal
• Pharmacokinetics
• Effectively absorbed from GI tract dogs/cats
• Uses severe skin infections (pyoderma),
  respiratory tract, urinary tract, prostate
  infections
• Extralabel use in horses caution in foals
• Avoid with antacids and sucralfate or give 4
  hours later
• They can exacerbate seizures
• SE
• bubble-like cartilage lesions in growing dogs (X5
  times higher dosage) contraindicated in
  small/medium size dogs of 2-8 months age Large
  breeds 12 months giant breeds 18 months
• Crystalluria
• Quinolone-induced blindness in cats (gt20mg/kg).
• Indiscriminate use may result in bacterial
  resistance Staphylococcus and Pseudomonas spp.
  Hence reserve for severe infections
• Cant use in food animals

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Antimetabolites

• Sulfonamides and Potentiated sulfonamides
  -static/cidal
• Are broad-spectrum antibiotics that inhibit the
  synthesis of folic acid (needed for the growth of
  many bacteria)
• Enteric forms or systemic forms
• Examples Bactericidal when potentiated with
  trimethoprim or ormetoprim gram organisms
  Streptococci, Staphylococci, Nocardia, Coccidia,
  Toxoplasma and Chlamydia
• sulfadimethoxine/ormetoprim (Primor)
• sulfadiazine/trimethoprim (Tribrissen)
• sulfadimethoxale/trimethoprim (human drug
  Septra)
• Sulfachlorpyridazine (livestock and poultry)
• Sulfasalazine (Azulfidine IBD). Enteric. More
  antiinflammatory effect esp in colon as
  aminosalicyclic acid. Caution in cat

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Antimetabolites

• Sulfonamides and Potentiated sulfonamides
  -static/cidal
• Pharmacokinetics
• Absorbed in monogastric GI tract
• Mostly lipophilic prostate, pleura, CSF, ocular,
  UTI
• Dont use in pregnant/ lactating animals
• Excreted kidney
• SE crystalluria (esp. older drugs), KCS (dry
  eye) can be irreversible, and skin rashes (most
  common) pruritus, hives, swelling face esp.
  Doberman pinschers, thrombocytopenia, leukopenia,
  anemia, cats profuse salivation
• Precipitate in kidneys of animals that are
  dehydrated or have acidic urine Adequate water
  intake very important!
• Antibiotic resistance

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Miscellaneous Agents

• Nitrofurans
• Are broad-spectrum antibiotics that include
  furazolidone, nitrofurantoin (Furadantin), and
  nitrofurantoin
• Used to treat wounds (topically) and urinary
  tract infections (not 1st choice)
• Filtered unchanged through kidneys
• Carcinogenic residues in animal tissues
• Nitroimiazoles
• Have antibacterial and antiprotozoal activity
  work by disrupting DNA and nucleic acid synthesis
• An example is metronidazole, which is considered
  by some the drug of choice for canine diarrhea

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• Metronidazole (Flagyl) is drug of choice for
  canine diarrhea
• Disrupt syn. of DNA and nucleic acids. Works with
  anaerobic bacteria
• Used to treat Giardia, Entamoeba histolytica,
  Balantidium and Trichomonas infections, deep
  puncture wounds
• Also used for amoebiasis and anaerobic bacteria
• Oral or intravascular administration
• No approved veterinary form of metronidazole
  (used off-label)
• Do not use in pregnant animals
• SE Can cause neurologic signs vestibular signs,
  tremors, seizures with oversose/ long periods of
  time

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Miscellaneous Agents

• Rifampin -cidal/static
• Disrupts RNA synthesis by inhibiting RNA
  polymerase
• Is broad-spectrum used in conjunction with other
  antibiotics (usually erythromycin) for
  Corynebacterium equi (Rhodococcus equi),
  Staphylococcus infections, Fungi? Histoplasma,
  Aspergillus, Blastomyces with amphotericin B
• May impart a reddish color to urine, tears,
  sweat, and saliva.
• Increases metabolism of propranolol, quinidine,
  chloramphenicol, diazepam, zolazepam (Telazol),
  phenobarbital, pentobarbital, prednisone and
  dexmathasone

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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.
• http//ahdc.vet.cornell.edu/clinpath/modules/ua-ro
  ut/castssed.htm