What is the appropriate colistimethate sodium (colistin) dosing regimen for an adult patient based on creatinine clearance?

Colistin Renal Dosing

All patients should receive a loading dose of 5 mg colistin base activity (CBA)/kg (approximately 9 million IU) intravenously regardless of renal function, followed by maintenance dosing calculated using the formula: 2.5 mg CBA × (1.5 × creatinine clearance + 30) mg every 12 hours. 1, 2

Loading Dose (Critical First Step)

• Administer 5 mg CBA/kg (≈9 million IU or 300 mg CBA) to ALL patients regardless of renal function 1, 2, 3
• The loading dose is essential because colistin has a long half-life relative to dosing intervals, and therapeutic levels take 2-3 days to achieve without it 1, 2
• For patients <60 kg body weight, use 6 million IU loading dose 3, 4
• In obese patients, calculate based on ideal body weight, not actual weight 3

Maintenance Dosing Based on Creatinine Clearance

Formula-Based Approach (Preferred)

Use this formula: 2.5 mg CBA × (1.5 × CrCl + 30) mg IV every 12 hours 1, 2

This formula automatically adjusts for renal function and is the most precise method recommended by recent guidelines.

Alternative FDA-Approved Dosing Table

If the formula is unavailable, use these FDA-approved adjustments 3:

Creatinine Clearance	Dosage
≥80 mL/min (normal)	2.5-5 mg/kg/day divided into 2-4 doses
50-79 mL/min (mild)	2.5-3.8 mg/kg divided into 2 doses daily
30-49 mL/min (moderate)	2.5 mg/kg once daily or divided into 2 doses
10-29 mL/min (severe)	1.5 mg/kg every 36 hours

Critically Ill Patients with Normal Renal Function

• For severe sepsis/septic shock with CrCl >50 mL/min: use 4.5 million IU (150 mg CBA) every 12 hours 1, 2
• This higher dose is necessary because standard dosing may be inadequate in critically ill patients with augmented renal clearance 5

Special Populations: Renal Replacement Therapy

Continuous Renal Replacement Therapy (CRRT)

• Give loading dose of 9 million IU, then maintenance dose of 3 million IU (100 mg CBA) every 8 hours 1, 2, 4
• Do NOT reduce the dose for CRRT—patients require at least 9 million IU daily total 1, 2
• CRRT removes approximately 28-41% of colistin, necessitating higher dosing than anuric patients 4

Intermittent Hemodialysis

• Give normal loading dose of 9 million IU, then 2 million IU every 12 hours 1, 2
• Schedule dialysis toward the END of the dosing interval to minimize drug removal 1, 2
• On non-dialysis days, use the standard formula based on residual creatinine clearance 5

Continuous Ambulatory Peritoneal Dialysis (CAPD)

• Loading dose: 300 mg CBA on day 1 6
• Maintenance: 150-200 mg CBA once daily 6
• CAPD clearance is minimal (0.088-0.101 L/h), so doses should not be increased 6

Administration Methods

• Administer maintenance doses as a slow IV infusion over 3-5 minutes for intermittent dosing 3
• Alternatively, use continuous infusion: give half the daily dose as bolus, then infuse the remaining half over 22-23 hours 3
• Consider 4-hour infusions to optimize pharmacokinetic/pharmacodynamic properties 2

Critical Monitoring Requirements

• Measure serum creatinine at baseline and 2-3 times per week during therapy 2, 7
• Monitor for acute kidney injury, which occurs in 29-44% of patients and is associated with clinical failure and mortality 2, 7
• Check electrolytes, particularly magnesium, as hypomagnesemia is common 2
• Avoid concurrent aminoglycosides when possible, as this dramatically increases nephrotoxicity risk 8

Important Dosing Conversions

• 1 million IU colistimethate sodium = 80 mg CMS = 33 mg colistin base activity (CBA) 1, 2, 3
• Always verify which unit your institution uses to avoid 2-3 fold dosing errors

Common Pitfalls to Avoid

• Never skip the loading dose—this is the most common error and results in subtherapeutic levels for 48-72 hours 1, 2
• Do not reduce maintenance doses in CRRT patients—they require full or near-full dosing 1, 4
• Patients with CrCl ≥80 mL/min may not achieve therapeutic levels even with maximum doses—strongly consider combination therapy in these patients 5
• Do not use colistin monotherapy for serious infections—combination with carbapenems or other agents (even if "resistant") improves outcomes 1, 2, 7

When Standard Dosing May Be Inadequate

• Pathogens with MIC ≥1 mg/L (especially Pseudomonas species) may require combination therapy 2, 9
• Patients with augmented renal clearance (CrCl >130 mL/min) often fail to achieve target concentrations with standard dosing 5
• Consider therapeutic drug monitoring if available, targeting steady-state trough concentrations ≥2.5 mg/L 4, 9