Polymyxin B Sulfate — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	Topical (otic, ophthalmic, dermal)	Apply 2-4 drops or a small amount to affected area	q6-12h (typically 2-4 times daily)	Duration: 5-7 days or as directed Notes: Use only for susceptible infections. Avoid prolonged use to prevent resistance.
Cat	Topical (otic, ophthalmic, dermal)	Apply 2-4 drops or a small amount to affected area	q6-12h	Duration: 5-7 days Notes: Same as dog.
Horse	Topical (ophthalmic, dermal)	Apply 2-4 drops or a small amount to affected area	q6-8h	Duration: 5-7 days Notes: For ophthalmic use, use sterile ophthalmic preparations.
Cattle (dairy)	Intramammary infusion	One syringe (typically 10-20 mL containing 100,000-200,000 IU polymyxin B) per affected quarter	q12h for 2-3 days	Duration: 2-3 days Notes: Often combined with other antibiotics. Observe milk withdrawal times.
Small Ruminants (sheep, goats)	Topical	Apply to affected area	q6-12h	Duration: 5-7 days Notes: Extra-label use; observe withdrawal times.
Rabbit	Topical (otic, ophthalmic, dermal)	Apply 1-2 drops or a small amount	q8-12h	Duration: 5-7 days Notes: Use caution to avoid systemic absorption.
Birds/Poultry	Topical	Apply to affected area	q8-12h	Duration: 5-7 days Notes: Not for systemic use. Avoid use in laying hens if eggs are for human consumption.

Clinical Indications & Species Uses

General Indications

Topical treatment of superficial infections of the skin, eye, and ear caused by susceptible Gram-negative bacteria
Intramammary infusion for mastitis in dairy cattle (often in combination)
Oral for GI decontamination (rarely used)

Dog (Canine)

Topical treatment of otitis externa caused by susceptible Gram-negative bacteria (e.g., Pseudomonas)
Topical treatment of skin infections (pyoderma, wounds) caused by susceptible organisms
Ophthalmic infections (conjunctivitis, keratitis) caused by susceptible Gram-negative bacteria
Oral administration for selective decontamination of the GI tract (e.g., in hepatic encephalopathy) - rarely used

Cat (Feline)

Topical treatment of otitis externa
Topical treatment of skin infections
Ophthalmic infections

Horse (Equine)

Topical treatment of superficial infections (wounds, dermatitis) caused by susceptible Gram-negative bacteria
Ophthalmic infections (as part of combination products)

Cattle (Bovine)

Topical treatment of mastitis (intramammary infusion) caused by susceptible Gram-negative bacteria (e.g., E. coli, Pseudomonas) - often in combination with other antibiotics

Small Ruminants (Sheep / Goat)

Topical treatment of superficial infections (wounds, dermatitis)
Intramammary infusion for mastitis (extra-label)

Rabbit & Small Mammals

Topical treatment of skin and eye infections caused by susceptible Gram-negative bacteria

Exotic & Other Species

Topical treatment of infections in reptiles, small mammals (e.g., guinea pigs, rats) caused by susceptible Gram-negative bacteria

Pharmacology & Mechanism of Action

Drug Class: Polymyxin antibiotic | Pharmacological Group: Polymyxin antibiotics

Mechanism of Action: Polymyxin B is a cationic polypeptide antibiotic that binds to the lipopolysaccharide (LPS) component of the outer membrane of Gram-negative bacteria. This binding disrupts the integrity of the bacterial cell membrane, increasing its permeability and leading to leakage of cellular contents and cell death. It is bactericidal against susceptible Gram-negative organisms, particularly Pseudomonas aeruginosa, and acts rapidly. Its action is primarily on the outer membrane, and it is not significantly absorbed systemically when applied topically or given orally.

Pharmacodynamics: Polymyxin B exhibits concentration-dependent bactericidal activity. It is active against many aerobic Gram-negative bacilli, including Pseudomonas aeruginosa, Escherichia coli, Klebsiella spp., Enterobacter spp., and Haemophilus influenzae. It is generally inactive against Gram-positive bacteria, fungi, and obligate anaerobes. Resistance is uncommon but can develop via modification of the LPS or efflux pumps. The drug is often used in combination with other antibiotics (e.g., trimethoprim, neomycin) to broaden spectrum and reduce resistance development.

⚡ Pharmacokinetics Summary

Absorption: Polymyxin B is poorly absorbed from the gastrointestinal tract, intact skin, and mucous membranes. When applied topically, systemic absorption is minimal. After intramuscular or intravenous administration, absorption is rapid and complete, but these routes are rarely used in veterinary medicine due to toxicity. Oral administration results in negligible systemic levels, making it useful for local GI decontamination.

Distribution: When systemically absorbed, polymyxin B distributes widely into tissues, but penetration into the central nervous system, eye, and joint spaces is poor. It is highly bound to tissue membranes and accumulates in the kidneys, liver, and spleen. It crosses the placenta but not significantly into milk.

Metabolism: Polymyxin B is not significantly metabolized; it is primarily excreted unchanged by the kidneys via glomerular filtration. Some degradation may occur in tissues, but metabolism is minimal.

Excretion: The primary route of elimination is renal excretion of unchanged drug. In patients with normal renal function, about 60% of an administered dose is recovered in urine within 24 hours. In renal impairment, accumulation can occur, increasing the risk of nephrotoxicity.

Half-Life: In dogs, the elimination half-life is approximately 1.5 to 2 hours after IV administration. In cats, it is similar. In patients with renal impairment, half-life is prolonged.

Bioavailability: Oral bioavailability is negligible (<1%). Topical absorption is minimal. Intramuscular and intravenous administration provide 100% bioavailability.

Protein Binding: Polymyxin B is approximately 50% protein-bound in plasma.

Available Formulations & Strengths

Ophthalmic solution/suspension 10,000 IU/mL (often combined with neomycin and bacitracin) (Ophthalmic)

Otic suspension 10,000 IU/mL (often combined with other antibiotics and anti-inflammatories) (Otic)

Topical cream/ointment 5,000-10,000 IU/g (often combined with neomycin and bacitracin) (Topical)

Intramammary infusion 100,000-200,000 IU per syringe (often combined with other antibiotics) (Intramammary)

Oral solution (for GI decontamination) Not commonly available; may be compounded (Oral)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to polymyxin B or any component of the formulation
Systemic use in animals with renal impairment (due to high nephrotoxicity)
Systemic use in animals with neuromuscular disorders (risk of neuromuscular blockade)
Do not use in horses intended for human consumption (no withdrawal time established)
Do not use intramammary in dry cows unless specifically indicated
Avoid use in animals with perforated tympanic membrane (for otic preparations) due to risk of ototoxicity

Warnings & Clinical Precautions:

For topical use only unless specifically indicated for oral or intramammary use; systemic absorption is minimal but can occur through broken skin or mucous membranes.
Prolonged use may lead to overgrowth of non-susceptible organisms, including fungi.
Use with caution in animals with renal disease; if systemic absorption is suspected, monitor renal function.
Avoid contact with eyes (for dermal preparations) unless ophthalmic formulation is used.
In food animals, observe withdrawal times; extra-label use requires veterinary oversight and extended withdrawal periods.
Polymyxin B can cause neuromuscular blockade; use with caution in animals with myasthenia gravis or when using neuromuscular blocking agents.
Do not use systemically in cats and rabbits due to high toxicity risk.

Adverse Effects & Reactions

Common:

Local irritation at application site (redness, itching)
Allergic contact dermatitis (rare but possible)

Serious / Severe:

Nephrotoxicity (if systemically absorbed)
Neurotoxicity (neuromuscular blockade, respiratory paralysis) - especially with systemic use
Ototoxicity (if used in ears with ruptured tympanic membrane)

Rare:

Anaphylaxis
Superinfection with resistant organisms

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Aminoglycosides (e.g., gentamicin, neomycin)	Additive nephrotoxicity and ototoxicity; also additive neuromuscular blocking effects.	High
Neuromuscular blocking agents (e.g., atracurium, succinylcholine)	Enhanced neuromuscular blockade, leading to respiratory depression.	High
Loop diuretics (e.g., furosemide)	Increased risk of ototoxicity and nephrotoxicity.	Moderate
NSAIDs (e.g., flunixin, meloxicam)	Potential additive nephrotoxicity if systemic absorption occurs.	Moderate
Cephalosporins	Possible additive nephrotoxicity.	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

Nephrotoxicity (increased BUN/creatinine, proteinuria)
Neurotoxicity (muscle weakness, ataxia, respiratory depression)
Apnea (with severe systemic overdose)
Local irritation at application site

Emergency Treatment Protocol: There is no specific antidote. Treatment is symptomatic and supportive. For systemic overdose, discontinue the drug, provide respiratory support (mechanical ventilation if needed), and maintain fluid balance to promote renal excretion. Monitor renal function closely. In cases of topical overdose, rinse the area with water. For oral overdose, consider gastric lavage if recent and large ingestion, but absorption is minimal. Hemodialysis may be considered in severe cases with renal failure, but efficacy is limited.

Food Animal Withdrawal Times

🥩 Meat: 7 days🥛 Milk: 3 days

Withdrawal times are not established for polymyxin B in all food animals. For cattle, when used as an intramammary infusion, milk withdrawal is typically 3-5 days and meat withdrawal 7-10 days, but must follow label or veterinary direction. For extra-label use, extended withdrawal periods should be applied (e.g., meat 14 days, milk 7 days). For poultry, do not use in laying hens if eggs are for human consumption.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 15-30°C (59-86°F). Protect from freezing.

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Protect from light. Keep container tightly closed. Do not use if solution is discolored or contains particulate matter.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Polymyxin B is FDA-approved for topical and ophthalmic use in animals (often in combination products). Intramammary preparations are approved for lactating dairy cattle. Systemic use is not approved in veterinary medicine.

Extra-Label (Off-Label) Use: In the US, extra-label use of polymyxin B in food animals is permitted under AMDUCA with veterinary oversight, but requires extended withdrawal times. It is prohibited in feed for food animals. In some countries, use in food animals may be restricted.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Polymyxin B is primarily used as a topical agent in veterinary medicine due to its excellent activity against Pseudomonas aeruginosa and other Gram-negative bacteria, and its poor systemic absorption. It is commonly found in combination products with neomycin and bacitracin (e.g., triple antibiotic ointments) for skin, eye, and ear infections. For otic use, it is important to ensure the tympanic membrane is intact to avoid ototoxicity. In dairy cattle, intramammary infusion is used for mastitis caused by Gram-negative organisms, but milk withdrawal must be observed. Systemic use is avoided due to severe nephrotoxicity and neurotoxicity. When using polymyxin B, always culture and sensitivity when possible to ensure susceptibility, and avoid prolonged use to minimize resistance development. In food animals, adhere to withdrawal times and extra-label regulations.

References & Literature

📚 Plumb's Veterinary Drug Handbook
📚 Papich Veterinary Pharmacology and Therapeutics
📚 Compendium of Veterinary Products (CVP)