Antimicrobials

CHAPTER 10-2CHAPTER 10-2

Dr. Dipa Brahmbhatt VMD MpHDr. Dipa Brahmbhatt VMD MpH

dbrahmbh@yahoo.comdbrahmbh@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

• BacitracinBacitracin – Disrupts the bacterial cell wall and is effective

against gram-positive bacteria– Used topically (skin, mucous membranes, eyes)

and as a feed additive– Nephrotoxic

• VancomycinVancomycin– Bacteriocidal; effective against many gram-

positive bacteria; used for resistant infections– Useful in treatment of Staphylococcus aureus

Cell Membrane Agents

• Polymyxin B 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

Protein Synthesis Agents• AminoglycosidesAminoglycosides– 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• AminoglycosidesAminoglycosides

– 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• AminoglycosidesAminoglycosides

– 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

– Don’t use in pregnant animals, geriatric patients, dehydration, shock or kidney disease

– NOT approved for use in food-producing animals.

Granular casts

Protein Synthesis Agents• Tetracyclines (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/ cephalosporinsTetracyclines: Don’t use with penicillins/ cephalosporins

• PharmacokineticsPharmacokinetics• 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: bacteriostaticChloramphenicol: 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. BacteriostaticFlorfenicol (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• MacrolidesMacrolides

– 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/staticLincosamides: -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: -cidalFluoroquinolones/ 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: -cidalFluoroquinolones/ Quinolones: -cidal

• PharmacokineticsPharmacokinetics• Effectively absorbed from GI tract dogs/catsEffectively absorbed from GI tract dogs/cats• Uses: severe skin infections (pyoderma), respiratory tract, urinary Uses: severe skin infections (pyoderma), respiratory tract, urinary

tract, prostate infectionstract, prostate infections• Extralabel use in horses: caution in foalsExtralabel use in horses: caution in foals• Avoid with antacids and sucralfate or give 4 hours laterAvoid with antacids and sucralfate or give 4 hours later• They can exacerbate seizuresThey can exacerbate seizures

– SE: SE: – bubble-like cartilage lesions in growing dogs (X5 times higher dosage): bubble-like cartilage lesions in growing dogs (X5 times higher dosage):

contraindicated in small/medium size dogs of 2-8 months age Large contraindicated in small/medium size dogs of 2-8 months age Large breeds: 12 months; giant breeds: 18 monthsbreeds: 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/cidalSulfonamides 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/cidalSulfonamides 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

• NitrofuransNitrofurans– 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

• NitroimiazolesNitroimiazoles– 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®) 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/staticRifampin: -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