Usage
Polymyxin B is an antibiotic primarily used to treat infections caused by gram-negative bacteria, particularly Pseudomonas aeruginosa. It is effective against Escherichia coli, Klebsiella pneumoniae, and Enterobacter aerogenes. It’s prescribed for conditions like urinary tract infections, meningitis, bacteremia, and eye infections. Its pharmacological classification is as a polypeptide antibiotic.
Polymyxin B works by disrupting the bacterial cell membrane. It binds to the negatively charged lipopolysaccharide in the outer membrane of gram-negative bacteria, altering its structure and permeability. This leads to leakage of intracellular contents and ultimately, bacterial cell death.
Alternate Names
Polymyxin B sulfate is an alternate name. Brand names include Polytrim (in combination with trimethoprim for ophthalmic use).
How It Works
Pharmacodynamics: Polymyxin B exerts its bactericidal effect by targeting the bacterial cell membrane. The disruption of the cell membrane causes leakage of cell contents, leading to bacterial death.
Pharmacokinetics:
- Absorption: Polymyxin B has poor oral absorption. It’s administered intravenously, intramuscularly, intrathecally (into the spinal canal), topically (for eye infections), or subconjunctivally (injection under the conjunctiva of the eye).
- Distribution: Its distribution in the body is limited, except for the kidneys. Negligible amounts cross the blood-brain barrier.
- Metabolism: It is not significantly metabolized.
- Excretion: Primarily excreted renally, necessitating dose adjustment in patients with renal impairment.
Mode of Action: Polymyxin B’s cationic nature enables it to bind to the anionic lipopolysaccharide molecules present in the outer membrane of gram-negative bacteria. This interaction disrupts the membrane’s structural integrity, causing increased permeability. The resultant leakage of essential intracellular components leads to cell death. Polymyxin B doesn’t involve receptor binding, enzyme inhibition, or neurotransmitter modulation in its mechanism of action.
Elimination pathways: Primarily renal excretion.
Dosage
Standard Dosage
Adults:
- Intravenous (IV): 15,000-25,000 units/kg/day, divided every 12 hours; not to exceed 25,000 units/kg/day.
- Intramuscular (IM): 25,000-30,000 units/kg/day, divided every 4-6 hours (not routinely recommended due to pain at the injection site).
- Intrathecal: 50,000 units daily for 3-4 days, then every other day for at least two weeks after CSF sterility and normalization of glucose are confirmed.
Children:
- IV: 15,000-40,000 units/kg/day, divided every 12 hours; not to exceed 25,000 units/kg/day.
- IM: 25,000-40,000 units/kg/day, divided every 4-6 hours (not routinely recommended).
- Intrathecal: (Under 2 years) 20,000 units daily for 3-4 days, then 25,000 units every other day; (Over 2 years) 50,000 units daily for 3-4 days, then every other day for at least two weeks after CSF sterility.
Special Cases:
- Elderly Patients: Monitor renal function and adjust dosage accordingly.
- Patients with Renal Impairment: Dosage reductions are necessary depending upon creatinine clearance.
- Patients with Hepatic Dysfunction: As it is primarily renally cleared, hepatic dysfunction doesn’t typically require dosage adjustments.
- Patients with Comorbid Conditions: Consider drug interactions with other medications.
Clinical Use Cases
Dosing in specific clinical settings follows standard recommendations and adjusts per special cases.
Dosage Adjustments
Adjustments are based on creatinine clearance, age, and other patient factors.
Side Effects
Common Side Effects:
- Nephrotoxicity (e.g., albuminuria, azotemia, cylindruria)
- Neurotoxicity (e.g., dizziness, drowsiness, paresthesias, flushing, ataxia)
- Pain at the injection site (IM)
Rare but Serious Side Effects:
- Apnea (especially with concurrent use of neuromuscular blocking agents)
- Anaphylaxis
Long-Term Effects:
- Renal damage with prolonged high-dose use
- Neurologic deficits with prolonged high-dose use
Adverse Drug Reactions (ADR): Neurotoxicity, nephrotoxicity, hypersensitivity.
Contraindications
- Hypersensitivity to polymyxin B
- Pre-existing renal dysfunction (severe)
- Concurrent use of other nephrotoxic or neurotoxic drugs (caution)
- Myasthenia gravis (caution)
Drug Interactions
- Neuromuscular blocking agents: Increased risk of respiratory paralysis
- Aminoglycosides & other nephrotoxic drugs (e.g., NSAIDs, cisplatin): Increased nephrotoxicity
- Cephalosporins: Increased risk of neurotoxicity
Pregnancy and Breastfeeding
- Pregnancy: Pregnancy Safety Category C (FDA): Use only if the potential benefit outweighs the risk. There’s limited data on its use in pregnancy. May interfere with folate metabolism, impacting fetal development.
- Breastfeeding: Excretion in breast milk unknown. Topical application is considered low risk. Use caution with other routes of administration.
Drug Profile Summary
- Mechanism of Action: Disrupts bacterial cell membrane permeability.
- Side Effects: Nephrotoxicity, neurotoxicity, injection site pain.
- Contraindications: Hypersensitivity, severe renal dysfunction.
- Drug Interactions: Neuromuscular blockers, aminoglycosides, nephrotoxic drugs.
- Pregnancy & Breastfeeding: Category C; use with caution. Topical application low risk.
- Dosage: Refer to the dosage section above.
- Monitoring Parameters: Renal function (BUN, creatinine), neurologic status.
Popular Combinations
- Trimethoprim: Often combined with polymyxin B for ophthalmic solutions (e.g., Polytrim), broadening the spectrum of antibacterial activity.
Precautions
- Monitor renal function closely, especially in elderly patients and those with pre-existing renal insufficiency.
- Reduce dosage in patients with renal impairment.
- Avoid concurrent use of nephrotoxic or neurotoxic drugs.
- Monitor for neurologic symptoms, such as paresthesias, ataxia, dizziness, and drowsiness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Polymyxin B?
A: Dosage varies according to the route of administration, the patient’s age, and renal function. Please refer to the detailed dosage section above.
Q2: What are the primary side effects of Polymyxin B?
A: Nephrotoxicity and neurotoxicity are the most significant side effects.
Q3: How does Polymyxin B work?
A: It disrupts the bacterial cell membrane, leading to cell death.
Q4: Can Polymyxin B be used during pregnancy?
A: It’s a Pregnancy Category C drug; use only if the potential benefit outweighs the risk. Consult a specialist.
Q5: What are the contraindications for Polymyxin B use?
A: Hypersensitivity to polymyxin B and severe renal dysfunction are major contraindications.
Q6: Does Polymyxin B interact with other medications?
A: Yes, it interacts with neuromuscular blocking agents, aminoglycosides, and other nephrotoxic drugs.
Q7: What should be monitored in patients receiving Polymyxin B?
A: Renal function (BUN, creatinine) and neurologic status should be monitored regularly.
Q8: Is Polymyxin B effective against all types of bacteria?
A: No, it is primarily effective against gram-negative bacteria, particularly Pseudomonas aeruginosa.
Q9: What is the route of administration for Polymyxin B?
A: It can be administered intravenously, intramuscularly, intrathecally, or topically (for eye infections).
