Colistin Dosing in Adults
For adult patients requiring colistin, administer a loading dose of 5 mg colistin base activity (CBA)/kg IV (equivalent to 9 million IU), followed by a maintenance dose calculated as 2.5 mg CBA × (1.5 × CrCl + 30) IV every 12 hours, with consideration of adjunctive inhaled colistin for ventilator-associated pneumonia. 1
Loading Dose
- All patients require a loading dose of 5 mg CBA/kg IV (approximately 9 million IU for most adults) regardless of renal function 1, 2
- The loading dose is critical because colistin has a relatively long half-life (14.4 hours) compared to the dosing interval, resulting in insufficient plasma concentrations before steady state is reached 2, 3
- For patients weighing <60 kg, reduce the loading dose to 6 million IU 4
Maintenance Dosing
Normal Renal Function
- Use the formula: 2.5 mg CBA × (1.5 × CrCl + 30) IV every 12 hours 1
- For critically ill patients with severe sepsis/septic shock and normal renal function, 4.5 million IU every 12 hours is appropriate 2
- Alternative dosing: 3 million IU every 8 hours has been studied and achieves therapeutic levels 4, 5
Renal Impairment
- Maintenance dose must be adjusted according to creatinine clearance using the formula above 1, 2
- For severe renal impairment, the National Kidney Foundation suggests 3.0-5.0 mg/kg IV every 24-36 hours 2
Continuous Renal Replacement Therapy (CRRT)
- Administer at least 9 million IU/day (3 million IU every 8 hours) for patients on CRRT 2, 4
- CRRT clearance accounts for approximately 41% of total CMS clearance and 28% of total colistin clearance 4
- A loading dose of 9 million IU followed by 3 million IU every 8 hours achieves therapeutic concentrations in patients undergoing continuous venovenous hemodialysis 4, 6
Intermittent Hemodialysis
- Administer 2 million IU every 12 hours with a normal loading dose 2
- Schedule dialysis toward the end of a colistin dosage interval 2
Adjunctive Inhaled Colistin for Ventilator-Associated Pneumonia
- For VAP caused by carbapenem-resistant pathogens sensitive only to polymyxins, consider adjunctive inhaled colistin in addition to IV therapy 7
- Refer to pneumonia-specific guidelines for inhaled colistin dosing 1
Important Conversion and Monitoring
Dosing Equivalence
- 1 million IU colistin methanesulfonate = 33 mg colistin base activity 1
- Alternatively stated: 1 million IU = 80 mg colistimethate sodium (CMS) 2, 8
- Colistin is administered as the inactive prodrug CMS, which is hydrolyzed in vivo to active colistin 2, 3
Renal Function Monitoring
- Monitor renal function at baseline and 2-3 times per week during treatment 2
- Nephrotoxicity occurs in approximately 36.2% of patients receiving colistin, representing a 2.4-fold increased risk compared to β-lactam-based regimens 9
- Most nephrotoxicity is reversible within one week of discontinuation 7
Administration Considerations
- Consider a 4-hour infusion to optimize pharmacokinetic/pharmacodynamic properties 2
- Target steady-state trough concentrations of at least 2.5 mg/L 4
- Therapeutic drug monitoring should be considered to ensure optimal dosing, particularly as subtherapeutic levels correlate with clinical failure 5
Critical Pitfalls to Avoid
- Do not omit the loading dose – plasma colistin concentrations remain insufficient before steady state without it, potentially leading to treatment failure 2, 3
- Do not use standard dosing for pathogens with MIC ≥1 mg/L – recommended doses may be inadequate, particularly for Pseudomonas species; strongly consider combination therapy in these cases 2
- Do not forget to adjust maintenance doses for renal function – failure to do so increases nephrotoxicity risk 1, 2
- Consider newer alternatives first – colistin should be regarded as a last-line agent; safer alternatives like ceftolozane-tazobactam or ceftazidime-avibactam should be used when the organism is susceptible 7
Alternative Consideration
- Polymyxin B may be preferred in patients with renal impairment or on CRRT as it requires no dose adjustment during CRRT and has lower nephrotoxicity rates (11.8% vs 39.3% with colistin) 7