Colistin Dosage and Administration for Multidrug-Resistant Gram-Negative Bacterial Infections
For treating multidrug-resistant gram-negative bacterial infections, colistin should be administered with a loading dose of 5 mg/kg of colistin base activity (CBA) IV, followed by a maintenance dose of 2.5 mg CBA × (1.5 × CrCl + 30) IV every 12 hours, with appropriate renal function adjustments. 1
Dosage Recommendations
Standard Dosing
- Loading dose: 5 mg/kg of colistin base activity (CBA) IV 1
- Maintenance dose: 2.5 mg CBA × (1.5 × CrCl + 30) IV every 12 hours 1
- Dosage equivalence: 1 million IU of colistin ≈ 33 mg of colistin base activity (CBA) or 80 mg of colistimethate sodium (CMS) 1
Renal Adjustment
Dosage should be modified based on renal function:
| Degree of Renal Impairment | Creatinine Clearance (mL/min) | Dosage Schedule |
|---|---|---|
| Normal | ≥80 | 2.5 to 5 mg/kg, divided into 2 to 4 doses per day |
| Mild | 50-79 | 2.5 to 3.8 mg/kg, divided into 2 doses per day |
| Moderate | 30-49 | 2.5 mg/kg, once daily or divided into 2 doses per day |
| Severe | 10-29 | 1.5 mg/kg every 36 hours |
Administration Methods
Intravenous Administration
Two options for IV administration:
Direct Intermittent Administration:
- Slowly inject one-half of the total daily dose over 3-5 minutes every 12 hours 2
Continuous Infusion:
- Inject one-half of the total daily dose over 3-5 minutes
- Add the remaining half to compatible IV solutions (0.9% NaCl, 5% dextrose, etc.)
- Administer by slow IV infusion over the next 22-23 hours 2
Reconstitution
- The 150 mg vial should be reconstituted with 2 mL Sterile Water for Injection
- This provides a concentration equivalent to 75 mg/mL colistin base activity 2
Treatment Duration
| Infection Type | Recommended Duration |
|---|---|
| Complicated UTI | 5-10 days |
| Complicated intra-abdominal infections | 5-10 days |
| VAP/HAP | 10-14 days |
| Bacteremia | 10-14 days |
Combination Therapy Considerations
For multidrug-resistant Acinetobacter baumannii (CRAB) infections:
- Avoid colistin-carbapenem combination therapy (strong recommendation against use; high certainty of evidence) 3
- Avoid colistin-rifampin combination therapy (strong recommendation against use, moderate certainty of evidence) 3
- For severe CRAB infections, consider combination therapy with two in vitro active antibiotics among available options (polymyxin, aminoglycoside, tigecycline, sulbactam combinations) 3
- For CRAB with meropenem MIC <8 mg/L, consider carbapenem combination therapy with high-dose extended-infusion carbapenem dosing 3
Efficacy and Safety Considerations
Efficacy
- Higher colistin doses (median 2.9 mg/kg/day vs 1.5 mg/kg/day) have been associated with improved microbiological success and 7-day survival 4
- Clinical response rates of 73-85% have been reported in studies using appropriate dosing regimens 5, 6
Safety Monitoring
- Nephrotoxicity: Close monitoring of renal function is essential as colistin can cause nephrotoxicity in 8-30% of patients 1
- Higher doses (median 3.8 mg/kg/day vs 1.6 mg/kg/day) have been associated with increased risk of acute kidney injury 4
- Monitor renal function regularly throughout treatment 1
Important Considerations
- In obese patients, dosing should be based on ideal body weight 2
- For critically ill patients, infectious disease consultation is strongly recommended 1
- The broth microdilution method is the reference standard for colistin susceptibility testing per CLSI and EUCAST guidelines 7
- Colistin should be reserved for infections proven or strongly suspected to be caused by susceptible bacteria due to its potential toxicity 1
Clinical Pearls
- Higher colistin doses are associated with better microbiological clearance but may increase nephrotoxicity risk, requiring careful balance 4
- Any final IV infusion solution containing colistimethate sodium should be freshly prepared and used within 24 hours 2
- Reconstituted solution for intramuscular injection should be refrigerated and used within 7 days 2