Colistin

# Colistin ## Overview - **Classification**: Polymyxin antibiotic - **Mechanism**: Cationic detergent that disrupts the integrity of bacterial cell membranes, leading to leakage of intracellular contents and cell death. Effective against Gram-negative bacteria. ## Primary Indications 1. **Multi-drug resistant (MDR) Gram-negative infections**: Salvage therapy for infections caused by *Pseudomonas aeruginosa*, *Acinetobacter baumannii*, *Klebsiella pneumoniae*. 2. **Cystic Fibrosis exacerbations**: Inhaled formulation used for chronic *P. aeruginosa* suppression. 3. **Catheter-related bloodstream infections**: Used as a component of salvage therapy. ## Adult Dosing ### Standard Dosing **Systemic Gram-negative Infections (e.g., VAP, BSI)** - **Note**: Doses are in **mg of colistimethate sodium (CMS)**. **1 mg CMS is approximately 0.33 mg colistin base activity (CBA)**. - **Loading Dose**: **270-300 mg CMS** (one-time dose) - **Maintenance Dose**: **2.5-5 mg CMS/kg/day** (based on ideal body weight) - **Frequency**: Divided into **2-4 doses per day** (e.g., q6-12h) - **Route**: IV infusion over 30-60 minutes - **Maximum Dose**: Typically **400 mg CMS/day** **Inhaled Dosing (Cystic Fibrosis for *P. aeruginosa* suppression)** - **Dose**: **75 mg** or **150 mg** (as CMS powder or solution) - **Frequency**: Twice daily - **Route**: Nebulized or dry powder inhaler - **Special Consideration**: May require pre-treatment with a bronchodilator to prevent bronchospasm. ### Dose Adjustments - **Renal Impairment**: Requires significant dose reduction. Consult current guidelines. - **CrCl 30-79 mL/min**: Loading dose as usual, then **2.5 mg CMS/kg/day** in 2-3 divided doses. - **CrCl <30 mL/min**: Loading dose as usual, then **1.5 mg CMS/kg/day** in 1-2 divided doses. - **Hemodialysis**: Dose **1.5 mg CMS/kg** 3 times weekly post-dialysis. - **CRRT**: Consult specialist; dosing highly variable. - **Hepatic Impairment**: No specific adjustments recommended. - **Elderly Patients**: Adjust based on renal function; often have age-related decline in CrCl. ## Pediatric Dosing - **Note**: Doses are in **mg of colistimethate sodium (CMS)**. **1 mg CMS is approximately 0.33 mg colistin base activity (CBA)**. ### Neonates (0-28 days) - **Dose**: **2.5-4 mg CMS/kg/day** - **Frequency**: Divided every 12 hours - **Maximum**: **4 mg CMS/kg/day** - **Special Notes**: Lower initial doses may be needed due to immature renal function; monitor closely for toxicity. ### Infants (1-12 months) - **Dose**: **2.5-5 mg CMS/kg/day** - **Frequency**: Divided every 8-12 hours - **Maximum**: **5 mg CMS/kg/day** (individualize based on response/toxicity) ### Children (1-12 years) - **Dose**: **2.5-5 mg CMS/kg/day** - **Frequency**: Divided every 8-12 hours - **Maximum**: Do not exceed adult maximums (e.g., **400 mg CMS/day**) ### Adolescents (13-18 years) - **Dose**: Follow **adult dosing regimen** (e.g., **2.5-5 mg CMS/kg/day** maintenance dose) - **Maximum**: Adult maximum dose (e.g., **400 mg CMS/day**) ## Safety Information ### Contraindications - **Absolute**: Hypersensitivity to colistin or polymyxins. - **Absolute**: Myasthenia gravis (due to risk of neuromuscular blockade). ### Common Adverse Effects - **Very Common (>10%)**: Nephrotoxicity (dose-dependent, acute kidney injury), Neurotoxicity (paresthesia, tingling around mouth, dizziness, vertigo). - **Common (1-10%)**: Rash, Pruritus, Fever, Gastrointestinal upset. - **Serious but Rare**: Respiratory paralysis (especially with rapid IV infusion or overdose), Anaphylaxis, Clostridioides difficile infection. ### Key Drug Interactions - **Nephrotoxic Drugs (e.g., Aminoglycosides, NSAIDs, Cyclosporine, Amphotericin B)**: Increased risk of severe nephrotoxicity. Avoid concurrent use if possible. - **Neuromuscular Blockers (e.g., Vecuronium, Rocuronium)**: Enhanced and prolonged neuromuscular blockade. Monitor for respiratory depression. - **Other Polymyxins (e.g., Polymyxin B)**: Additive toxicity, avoid concurrent use. ## Monitoring & Follow-up - **Before Treatment**: Baseline renal function (SCr, BUN, CrCl), Urinalysis, Electrolytes. - **During Treatment**: - **Renal function**: Daily SCr, BUN, urine output, CrCl (at least 3 times/week). - **Neurotoxicity**: Monitor for paresthesias, dizziness, muscle weakness, visual disturbances. - **Serum Colistin Levels**: If available, may be useful, especially in renal impairment or critical illness. - **Clinical Signs**: Monitor for signs of infection improvement or worsening toxicity (e.g., decreased urine output, new neurologic symptoms). ## Clinical Pearls - 💡 **Dosing Complexity**: Always confirm units (CMS vs. CBA). Most product labels use **CMS**. Be aware of the **1 mg CMS ≈ 0.33 mg CBA** conversion. - 💡 **Nephrotoxicity**: This is the primary dose-limiting toxicity. Ensure adequate hydration and careful renal function monitoring. - 💡 **Loading Dose**: An IV loading dose is often crucial to achieve therapeutic levels quickly due to its low volume of distribution. - 💡 **Inhaled Route**: Inhaled colistin can cause coughing or bronchospasm. Pre-treatment with a bronchodilator may be beneficial. - 💡 **Reconstitution**: Colistimethate sodium powder for injection must be carefully reconstituted with sterile water for injection before administration. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.