Colistimethate Sodium

Usage

Colistimethate sodium is a polymyxin antibiotic used to treat infections caused by multi-drug resistant Gram-negative bacteria. It is particularly effective against Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli, especially when these bacteria are resistant to other antibiotics. It is also used in patients with cystic fibrosis for chronic suppressive therapy of P. aeruginosa lung infections. Its pharmacological classifications include antibiotic and antibacterial. Colistimethate sodium disrupts the bacterial cell membrane, leading to cell death.

Alternate Names

Colistimethate sodium is also known as colistin methanesulfonate sodium. Brand names include Coly-Mycin M, Promixin, and Colomycin.

How It Works

Pharmacodynamics: Colistimethate is a prodrug that is hydrolyzed in vivo to colistin. Colistin acts as a cationic detergent, disrupting the bacterial cytoplasmic membrane, increasing permeability, and causing cell death. This effect is bactericidal.

Pharmacokinetics:

• Absorption: Colistimethate is poorly absorbed orally; therefore, parenteral administration is necessary for systemic infections. When administered intravenously or intramuscularly, colistimethate is distributed to various tissues.
• Metabolism: Colistimethate is hydrolyzed to colistin, its active form, in bodily fluids.
• Elimination: Colistin is primarily excreted by the kidneys. Dosage adjustments are required in patients with renal impairment.

Mode of Action: Colistin interacts with the lipopolysaccharide and phospholipids of the bacterial outer membrane. This interaction displaces divalent cations (calcium and magnesium), disrupting the integrity of the membrane and leading to increased permeability and leakage of cellular contents, ultimately resulting in bacterial cell death.

Dosage

Dosage is expressed in international units (IU) of colistimethate sodium (CMS) or milligrams (mg) of colistin base activity (CBA).

Standard Dosage

Adults:

• Intravenous/Intramuscular: 9 million IU CMS/day (equivalent to approximately 720 mg CMS or 297 mg CBA) divided into 2–3 doses. A loading dose of 9 MIU CMS may be given in critically ill patients.
• Nebulized: 1-2 million IU twice daily (BID) or three times daily (TID). Maximum 6 million IU daily.
• Inhaled Powder: 1.6625 MIU BID.

Children:

• Intravenous/Intramuscular: Children weighing ≤ 40 kg: 75,000–150,000 IU CMS/kg/day in 3 divided doses. Children weighing > 40 kg: Same as adult dose. A loading dose is given to critically ill children, similar to adults.
• Nebulized: <2 years: 0.5–1 million IU BID (max 2 million IU/day). ≥2 years: Same as adult dose.
• Inhaled Powder: ≥6 years: Same as adult dose.

Special Cases:

• Elderly Patients: Dose adjustments based on renal function are crucial.
• Patients with Renal Impairment: Dose reduction is required. Various guidelines exist, and consultation with an infectious disease specialist is recommended.
• Patients with Hepatic Dysfunction: No dosage adjustment is typically recommended.
• Patients with Comorbid Conditions: Use with caution in patients with myasthenia gravis, neuromuscular disorders, or those receiving other nephrotoxic or neurotoxic drugs.

Clinical Use Cases

The dosage guidelines provided above apply to various clinical settings, including those listed below. Note: Inhaled administration is specifically for pulmonary infections in cystic fibrosis patients.

• Intubation: Systemic (IV/IM) administration according to standard guidelines.
• Surgical Procedures: Systemic administration for prophylaxis or treatment according to standard guidelines.
• Mechanical Ventilation: Systemic administration according to standard guidelines.
• Intensive Care Unit (ICU) Use: Systemic administration, often with a loading dose, according to standard guidelines.
• Emergency Situations: Systemic administration according to standard guidelines.

Dosage Adjustments

Dose adjustments are based primarily on creatinine clearance, and recommendations vary. Consultation with an infectious disease specialist or pharmacist is highly recommended. Therapeutic drug monitoring (TDM) can be helpful in optimizing dosage and minimizing toxicity.

Side Effects

Common Side Effects

• Nephrotoxicity (renal impairment)
• Neurotoxicity (numbness, tingling, dizziness, vertigo, slurred speech, ataxia, confusion, seizures)
• Nausea and vomiting
• Upset stomach

Rare but Serious Side Effects

• Respiratory distress or arrest (particularly with inhaled administration or in patients with renal impairment)
• Neuromuscular blockade
• Anaphylaxis
• Clostridioides difficile-associated colitis

Long-Term Effects

• Chronic kidney disease (with prolonged use)
• Peripheral neuropathy

Adverse Drug Reactions (ADR)

• Acute kidney injury
• Respiratory paralysis
• Seizures

Contraindications

• Hypersensitivity to colistimethate sodium, colistin, polymyxin B, or any component of the formulation
• Myasthenia gravis (relative contraindication)

Drug Interactions

Colistimethate can interact with numerous drugs, including:

• Nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, vancomycin): Increased risk of nephrotoxicity.
• Neurotoxic drugs (e.g., other polymyxins): Increased risk of neurotoxicity.
• Neuromuscular blocking agents (e.g., atracurium, pancuronium): Potentiated neuromuscular blockade, increasing the risk of respiratory paralysis.
• Cephalosporins: Increased risk of nephrotoxicity.

Pregnancy and Breastfeeding

Colistimethate crosses the placenta. Animal studies have shown evidence of teratogenicity. It is recommended for use during pregnancy only if the benefits outweigh the potential risks. Colistimethate is excreted in breast milk in low amounts. Caution should be used when administering to breastfeeding women.

Drug Profile Summary

• Mechanism of Action: Disrupts bacterial cell membrane integrity.
• Side Effects: Nephrotoxicity, neurotoxicity, nausea, vomiting.
• Contraindications: Hypersensitivity to colistimethate, colistin, or polymyxin B; myasthenia gravis.
• Drug Interactions: Nephrotoxic and neurotoxic drugs, neuromuscular blocking agents.
• Pregnancy & Breastfeeding: Use with caution during pregnancy only if benefits outweigh risks; caution is advised during breastfeeding.
• Dosage: See detailed dosage guidelines above.
• Monitoring Parameters: Renal function (serum creatinine, BUN), neurologic status.

Popular Combinations

Colistimethate is often used in combination with other antibiotics, particularly for multi-drug resistant infections. Combinations may include other beta-lactams (e.g., meropenem, ceftazidime/avibactam) or other agents based on the specific pathogen’s susceptibility profile.

Precautions

• General Precautions: Monitor renal function and neurologic status. Assess for drug allergies and history of myasthenia gravis.
• Specific Populations: See above for adjustments in elderly patients, renal impairment, and pregnancy/breastfeeding. Use with extreme caution in neonates.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Colistimethate Sodium?

A: See the detailed dosage guidelines above. Dosage depends on patient age, weight, renal function, and the severity of the infection.

Q2: What is the mechanism of action of colistimethate?

A: Colistimethate is a prodrug hydrolyzed to colistin, which disrupts the bacterial cell membrane, leading to cell death.

Q3: What are the common side effects of colistimethate?

A: Nephrotoxicity and neurotoxicity are the most common serious side effects. Other side effects include nausea, vomiting, and dizziness.

Q4: What are the contraindications for using colistimethate?

A: Hypersensitivity to colistin or polymyxin B and myasthenia gravis are contraindications.

Q5: How is colistimethate administered?

A: Colistimethate can be administered intravenously, intramuscularly, via inhalation (for pulmonary infections in cystic fibrosis patients), or nebulized.

Q6: What are the key drug interactions with colistimethate?

A: Concomitant use with other nephrotoxic or neurotoxic medications (e.g., aminoglycosides, amphotericin B) can increase the risk of renal or neurological adverse effects. Neuromuscular blocking agents should also be used with caution.

Q7: Is Colistimethate safe during pregnancy?

A: Colistimethate crosses the placenta. Animal studies show potential risks. Use during pregnancy only if clearly needed and after careful consideration of the risks and benefits.

Q8: How should I monitor patients receiving colistimethate?

A: Monitor renal function (serum creatinine, BUN) regularly, especially in the first week of treatment. Assess neurologic status frequently. Therapeutic drug monitoring may also be beneficial.

Q9: What are the signs of colistimethate neurotoxicity?

A: Numbness, tingling of extremities, slurred speech, dizziness, vertigo, confusion, psychosis, and seizures. Neuromuscular blockade may also occur.

Q10: What should I do if a patient develops nephrotoxicity while on colistimethate?

A: Discontinue colistimethate or reduce the dose, depending on the severity of the nephrotoxicity and the clinical situation. Consult with a nephrologist or infectious disease specialist.

Please note that this information is current as of February 16, 2025, and is intended for use by qualified medical professionals. Always consult up-to-date resources and clinical guidelines before making treatment decisions.