1. Clinical Overview
Colistimethate Sodium is a polymyxin antibiotic, specifically polymyxin E, used as a last-line therapeutic agent for the treatment of severe, multidrug-resistant Gram-negative bacterial infections, particularly those caused by Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. It is a prodrug hydrolyzed in vivo to the active form, colistin. Its use is reserved for situations where other safer antibiotics are ineffective or contraindicated due to its significant nephrotoxicity and neurotoxicity potential.
| Onset | Duration | Bioavailability |
|---|---|---|
| Peak serum concentrations are reached within 1-2 hours after completion of an intravenous infusion. | The dosing interval is typically every 8-12 hours due to a post-antibiotic effect and concentration-dependent killing. | Approximately 0% orally; it is not absorbed from the gastrointestinal tract. For systemic effect, it must be administered intravenously or via inhalation. |
2. Mechanism of Action
Colistimethate Sodium is a prodrug that is converted to colistin. Colistin acts as a cationic detergent. Its lipophilic fatty acid chain interacts with the lipopolysaccharide (LPS) of the outer membrane of Gram-negative bacteria, displacing magnesium and calcium bridges that stabilize the LPS. This disrupts the integrity of the outer membrane, allowing the polycationic peptide ring to penetrate and interact with the cytoplasmic membrane, leading to increased permeability, leakage of cellular contents, and ultimately bacterial cell death.
3. Indications & Uses
- Severe infections caused by multidrug-resistant (MDR) Gram-negative bacilli: Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae.
- Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) caused by susceptible MDR organisms.
- Bloodstream infections (bacteremia/sepsis) due to carbapenem-resistant Enterobacteriaceae (CRE).
- Complicated urinary tract infections (cUTI) and pyelonephritis caused by MDR Gram-negative bacteria.
4. Dosage & Administration
Adult Dosage: IV: Loading dose of 9 million IU, followed by a maintenance dose of 4.5 million IU every 12 hours for patients with normal renal function (eGFR >80 mL/min/1.73m²). Dosing is weight-based: 3-5 mg/kg/day (approx. 37,500-62,500 IU/kg/day) in 2-3 divided doses. Always refer to specific hospital protocol and renal function.
Administration: For IV use only. Reconstitute 1 Million IU vial with 2-4 mL of Sterile Water for Injection. Further dilute in 50-100 mL of compatible IV fluid (0.9% NaCl or 5% Dextrose). Infuse over 30-60 minutes. Incompatible with many drugs; administer separately. For inhalation: Reconstitute with sterile saline as per specific nebulizer guidelines.
5. Side Effects
Common side effects may include:
- Nephrotoxicity (rise in serum creatinine, reduced urine output) - occurs in up to 50% with traditional dosing.
- Neurotoxicity: dizziness, vertigo, circumoral and peripheral paresthesia.
- Injection site reactions: pain, phlebitis.
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Aminoglycosides (Gentamicin, Amikacin) | Additive/synergistic nephrotoxicity and ototoxicity. | Major |
| Loop Diuretics (Furosemide) | May enhance nephrotoxic potential. | Moderate |
| Neuromuscular Blocking Agents (Succinylcholine, Vecuronium) | Potentiates neuromuscular blockade, risk of prolonged apnea and respiratory depression. | Major |
| Vancomycin | Increased risk of nephrotoxicity. | Moderate |
| NSAIDs (e.g., Ibuprofen, Diclofenac) | Increased risk of nephrotoxicity. | Moderate |
7. Patient Counselling
- DO complete the full course of therapy as prescribed, even if you feel better.
- DO inform all your doctors about all medications you are taking, including over-the-counter drugs.
- DO maintain adequate hydration unless advised otherwise by your doctor.
- DO NOT skip doses.
- DO NOT adjust the dose or stop the medication without consulting your doctor.
- DO NOT take any other painkillers (like ibuprofen, diclofenac) without asking your doctor.
8. Toxicology & Storage
Overdose: Manifestations of overdose are extensions of its toxicities: acute renal failure, neuromuscular blockade (muscle weakness, apnea), confusion, seizures, and paresthesias.
Storage: Store unopened vials at controlled room temperature (15-25°C), protected from light and moisture. After reconstitution with Sterile Water for Injection, the solution is stable for up to 24 hours if refrigerated at 2-8°C. For IV infusion, use the diluted solution immediately or within 24 hours if stored refrigerated. Do not freeze.