Colistin Dosage and Treatment Duration for Multidrug-Resistant Gram-Negative Bacterial Infections
For multidrug-resistant gram-negative bacterial infections, colistin should be administered with a loading dose of 5 mg/kg colistin base activity (CBA) IV, followed by a maintenance dose of 2.5 mg CBA × (1.5 × CrCl + 30) IV every 12 hours, with treatment duration ranging from 5-14 days depending on the infection site. 1
Dosing Recommendations
Standard Dosing
- Loading dose: 5 mg/kg of colistin base activity (CBA) IV administered over 0.5-1 hour 1
- Maintenance dose: 2.5 mg CBA × (1.5 × CrCl + 30) IV every 12 hours 2, 1
- Conversion factor: 1 million IU of colistin ≈ 33 mg of colistin base activity (CBA) 2, 1
Renal Adjustment
Dose adjustment is required based on renal function 3:
| Degree of Renal Impairment | Creatinine Clearance (mL/min) | Dosage Schedule |
|---|---|---|
| Normal | ≥80 | 2.5 to 5 mg/kg/day, divided into 2-4 doses |
| Mild | 50-79 | 2.5 to 3.8 mg/kg/day, divided into 2 doses |
| Moderate | 30-49 | 2.5 mg/kg/day, once daily or divided into 2 doses |
| Severe | 10-29 | 1.5 mg/kg every 36 hours |
Treatment Duration
Treatment duration varies by infection type 2, 1:
- Complicated urinary tract infections: 5-7 days
- Complicated intra-abdominal infections: 5-7 days
- Hospital-acquired or ventilator-associated pneumonia: 10-14 days
- Bloodstream infections: 10-14 days
Specific Infection Scenarios
Carbapenem-Resistant Enterobacterales (CRE)
For bloodstream infections due to CRE, colistin-based combinations are recommended 2:
- Colistin 5 mg CBA/kg IV loading dose, then 2.5 mg CBA (1.5 CrCl + 30) IV q12h + Tigecycline 100 mg IV loading dose, then 50 mg IV q12h, or
- Colistin + Meropenem 1 g IV q8h by extended infusion
- Treatment duration: 7-14 days
Carbapenem-Resistant Pseudomonas aeruginosa (CRPA)
For infections due to difficult-to-treat P. aeruginosa (DTR-PA) 2:
- Colistin monotherapy or combination therapy
- Treatment duration: 5-14 days
Administration Methods
Intravenous Administration 3
- Direct Intermittent Administration: Slowly inject one-half of the total daily dose over 3-5 minutes every 12 hours
- Continuous Infusion: Inject half the daily dose over 3-5 minutes, then infuse remaining half over next 22-23 hours
Intramuscular Administration 3
- Administer by deep intramuscular injection into a large muscle mass
- Store reconstituted solution in refrigerator and use within 7 days
Efficacy and Safety Considerations
Efficacy
- Higher colistin doses (median 2.9 vs 1.5 mg/kg/day) have been associated with better microbiological success rates 4
- Clinical cure rates of 62.5-84.6% have been reported across different infection types 5
Safety Monitoring
- Nephrotoxicity is the primary concern, occurring in 8.3-20% of patients 6, 5
- Risk factors for nephrotoxicity include:
Alternative Therapies
When available and susceptible, newer agents are preferred over colistin due to better safety profiles 1:
- Ceftolozane-tazobactam
- Ceftazidime-avibactam
- Imipenem-cilastatin-relebactam
Clinical Pitfalls to Avoid
Inadequate loading dose: Failure to administer a loading dose can result in delayed achievement of therapeutic concentrations and poorer outcomes 1
Incorrect dose calculations: Confusion between colistin base activity (CBA) and colistimethate sodium (CMS) can lead to dosing errors 1, 3
Insufficient renal monitoring: Regular monitoring of renal function is essential due to nephrotoxicity risk 1
Monotherapy for severe infections: Consider combination therapy for severe infections, particularly bloodstream infections and pneumonia 2, 1
Inappropriate treatment duration: Inadequate treatment duration can lead to treatment failure, while excessive duration increases toxicity risk 2