Antimicrobials
CHAPTER 10-2
Dr. Dipa Brahmbhatt VMD MpH
dbrahmbh@yahoo.com
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
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 grampositive bacteria; used for resistant infections
– Useful in treatment of Staphylococcus aureus
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, grampositive 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
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
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 > ECF: volume of distribution is larger
in neonates/ young animals > 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
Protein Synthesis Agents
• Aminoglycosides
– Side effects are nephrotoxicity and
Ototoxicity: cats sensitive, vestibular signs;
Granular casts
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
– Don’t use in pregnant animals, geriatric patients,
dehydration, shock or kidney disease
– NOT approved for use in food-producing animals.
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
Protein Synthesis Agents
•
Tetracyclines: Don’t 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: DON’T GIVE TO HORSES, cardiac arrhythmias,
collapse, death
• Oxt/tetracycline: hydrophilic. Expired products > 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. Cat’s 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
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.
– Don’t 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
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
– Don’t use in breeding animals
Protein Synthesis Agents
•
•
Macrolides
– Interfere with the production of protein in bacterial cells
– Are broad-spectrum antibiotics that have a large molecular structure. Don’t
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)
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
– DON’T 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.
Nucleic Acid Agents
• Fluoroquinolones/ Quinolones: -cidal
– Are antibiotics with fluorine bound to the quinolone base, which
increases the drug’s 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. DON’T 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
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 (>20mg/kg).
– Indiscriminate use may result in bacterial resistance:
Staphylococcus and Pseudomonas spp. Hence reserve for severe
infections
– Can’t use in food animals
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
Antimetabolites
• Sulfonamides and Potentiated sulfonamides: -static/cidal
– Pharmacokinetics
– Absorbed in monogastric GI tract
– Mostly lipophilic: prostate, pleura, CSF, ocular, UTI
– Don’t 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
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
• 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
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
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
-rout/castssed.htm