Usage
Colistin Sulphate is prescribed for infections caused by multidrug-resistant (MDR) Gram-negative bacteria, especially when other antibiotics are ineffective. It is primarily used for serious infections like pneumonia (including ventilator-associated pneumonia), bloodstream infections, and complicated urinary tract infections. It is also used in cystic fibrosis patients with Pseudomonas aeruginosa lung infections.
Its pharmacological classification is antibiotic, specifically a polymyxin antibiotic.
Colistin works by disrupting the bacterial cell membrane, leading to bacterial cell death.
Alternate Names
- Colistin
- Colistin Sulphomethate Sodium (alternate salt form)
- Polymyxin E
- Colistimethate sodium (CMS)
Brand names vary depending on the region and manufacturer. Some examples include Colomycin®, Coly-Mycin M® and Promixin®.
How It Works
Pharmacodynamics: Colistin acts as a cationic detergent, disrupting the outer and inner cell membranes of Gram-negative bacteria. This causes increased permeability, leakage of cellular contents, and ultimately, bacterial death. It primarily targets the lipopolysaccharide (LPS) component of the outer membrane. Colistin is bactericidal, meaning it directly kills bacteria.
Pharmacokinetics:
- Absorption: Poorly absorbed orally in the gastrointestinal tract. Administered intravenously (IV) or intramuscularly (IM) for systemic infections, and by inhalation for lung infections.
- Distribution: Distributes widely into tissues, but penetration into the central nervous system (CNS) is limited.
- Metabolism: Colistimethate sodium (prodrug) is hydrolyzed in vivo to colistin (active form), which is further metabolized.
- Elimination: Primarily eliminated by the kidneys (renal excretion). Dose adjustments are necessary for patients with renal impairment.
Mode of Action: Colistin binds to the LPS in the outer membrane of Gram-negative bacteria, displacing divalent cations (calcium and magnesium) that stabilize the membrane structure. This destabilizes the outer membrane, leading to increased permeability. Colistin can then interact with the inner cytoplasmic membrane, causing further disruption and leakage of cellular contents, resulting in bacterial death. This mechanism makes it effective against many MDR bacteria.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Colistin’s primary mechanism is membrane disruption. It does not directly bind to specific receptors, inhibit enzymes, or modulate neurotransmitters.
Dosage
Dosage is provided in terms of Colistin base activity (CBA).
Standard Dosage
Adults:
- IV/IM: 2.5 to 5 mg/kg/day of CBA, divided every 6-12 hours. Maximum dose: 5 mg/kg/day.
- Inhalation: 75 mg or 150 mg of CBA every 12 hours. For ventilator-associated pneumonia: 150 mg every 8 hours may be used.
Children:
- IV/IM: Dosing guidelines vary. Some sources recommend 2.5 mg/kg/day divided every 6-12 hours. However, other sources mention alternative regimens or suggest avoiding use in children under a certain age or weight. It’s crucial to consult specific pediatric guidelines and tailor dosing based on the child’s age, weight, and renal function.
- Inhalation: 30 mg or 75 mg of CBA every 12 hours.
Special Cases:
- Elderly Patients: Caution is advised, particularly with renal function monitoring, as elderly patients are more susceptible to nephrotoxicity.
- Patients with Renal Impairment: Dosage adjustments are crucial, based on creatinine clearance (CrCl). Refer to specialized resources for detailed adjustments based on various CrCl ranges.
- Patients with Hepatic Dysfunction: No specific adjustments are typically recommended, but caution is advised.
- Patients with Comorbid Conditions: Consider individual patient factors like diabetes, cardiovascular disease, neuromuscular disorders (e.g., myasthenia gravis) when determining the dosage.
Clinical Use Cases
Dosing generally follows the standard adult recommendations and adjustments based on renal function and other patient-specific factors. Always consult updated clinical guidelines and expert recommendations for specific use cases.
Dosage Adjustments
Dose modifications are essential in renal impairment. Special considerations are needed for patients with metabolic disorders or genetic polymorphisms affecting drug metabolism. Refer to a specialized resource for specific recommendations.
Side Effects
Common Side Effects
- Nephrotoxicity (kidney damage)
- Neurotoxicity (numbness, tingling, dizziness, vertigo, seizures)
- Nausea, vomiting, diarrhea
Rare but Serious Side Effects
- Respiratory failure (especially with inhaled colistin)
- Anaphylaxis (severe allergic reaction)
- Neuromuscular blockade (muscle weakness or paralysis)
Long-Term Effects
Chronic kidney disease can occur with prolonged use, especially in those with pre-existing renal impairment.
Adverse Drug Reactions (ADR)
Nephrotoxicity and neurotoxicity are clinically significant ADRs requiring careful monitoring and potential dose adjustment or discontinuation.
Contraindications
- Hypersensitivity to colistin or polymyxins
- Myasthenia gravis (a neuromuscular disorder)
Drug Interactions
Colistin can interact with several medications:
- Neuromuscular blocking agents: Increased risk of respiratory paralysis.
- Nephrotoxic drugs (e.g., aminoglycosides, vancomycin, amphotericin B): Increased risk of kidney damage.
- Cephalosporins: Potential increased risk of nephrotoxicity.
Refer to a detailed drug interaction resource for a complete list.
Pregnancy and Breastfeeding
- Pregnancy: Colistin crosses the placental barrier. Use with caution only if the potential benefit outweighs the potential risk to the fetus. Pregnancy Safety Category C.
- Breastfeeding: Colistin is excreted in breast milk. Exercise caution when administering to breastfeeding women.
Drug Profile Summary
- Mechanism of Action: Disrupts bacterial cell membranes, leading to bacterial cell death.
- Side Effects: Nephrotoxicity, neurotoxicity, nausea, vomiting, diarrhea.
- Contraindications: Hypersensitivity, myasthenia gravis.
- Drug Interactions: Neuromuscular blockers, nephrotoxic drugs, cephalosporins.
- Pregnancy & Breastfeeding: Use with caution; crosses placenta and is present in breast milk.
- Dosage: Refer to the detailed dosage section above.
- Monitoring Parameters: Renal function tests (serum creatinine, BUN), neurological status.
Popular Combinations
Information on specific popular combinations for India is limited in the provided sources. Generally, colistin might be combined with other antibiotics based on the specific infection and bacterial susceptibility.
Precautions
- General Precautions: Renal function monitoring is essential. Assess for pre-existing neurological conditions.
- Specific Populations: As detailed in the dosage section.
- Lifestyle Considerations: Caution patients against driving or operating machinery if experiencing neurotoxic effects like dizziness. Alcohol interaction information is limited.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Colistin Sulphate?
A: See the detailed dosage section above, which covers adult, pediatric, and special population dosing.
Q2: What are the most serious side effects of Colistin Sulphate?
A: Nephrotoxicity and neurotoxicity are the most serious side effects. Respiratory failure can occur with the inhaled formulation. Anaphylaxis is a rare but serious side effect.
Q3: How does renal impairment affect Colistin Sulphate dosing?
A: Dose reduction is crucial in patients with renal impairment. Consult specific guidelines or dosing nomograms based on creatinine clearance to adjust the dosage appropriately.
Q4: Can Colistin Sulphate be used during pregnancy or breastfeeding?
A: Colistin should be used with caution during pregnancy and breastfeeding, only if the potential benefit justifies the potential risk to the fetus or neonate.
Q5: What infections is Colistin Sulphate typically used to treat?
A: Colistin is used for serious infections caused by MDR Gram-negative bacteria, particularly when other antibiotic options are limited.
Q6: How is Colistin Sulphate administered?
A: It can be administered intravenously, intramuscularly, or by inhalation, depending on the site and severity of infection.
Q7: How does Colistin Sulphate differ from other antibiotics?
A: It belongs to the polymyxin class, which has a distinct mechanism of action (membrane disruption) compared to many other antibiotic classes. It’s often reserved for MDR bacteria resistant to other antibiotics.
Q8: What should I monitor in patients receiving Colistin Sulphate?
A: Monitor renal function (serum creatinine, BUN) and neurological status closely. Look for signs of nephrotoxicity or neurotoxicity, and adjust the dosage or discontinue treatment as needed.
Q9: Are there any specific contraindications to using Colistin Sulphate?
A: Known hypersensitivity to colistin or polymyxins, and myasthenia gravis are contraindications.
