What is the appropriate colistin (polymyxin E) dosing regimen, including loading dose and maintenance adjustments, for a patient with acute kidney injury and varying creatinine clearance or on dialysis?

Colistin Dosing in Acute Kidney Injury

All patients with AKI should receive a loading dose of 9 million IU (≈5 mg/kg colistin base activity) regardless of renal function, followed by maintenance doses calculated using the formula: 2.5 mg CBA × (1.5 × creatinine clearance + 30) mg every 12 hours, adjusted for the specific creatinine clearance or dialysis modality. 1

Loading Dose (Universal for All AKI Patients)

• Administer 9 million IU (≈5 mg/kg CBA) intravenously to every patient, regardless of degree of renal impairment 1, 2
• The loading dose is critical because colistin's long half-life would otherwise delay therapeutic levels for 48-72 hours, leading to subtherapeutic exposure during this vulnerable period 1
• Never omit the loading dose in AKI patients—failure to load results in delayed therapeutic concentrations and increased risk of treatment failure 1

Maintenance Dosing Based on Creatinine Clearance

Formula-Based Approach (Preferred Method)

• Use the equation: Maintenance dose (mg CBA) = 2.5 × (1.5 × CrCl [mL/min] + 30), administered every 12 hours IV 1
• This formula automatically adjusts for varying degrees of renal impairment and is the most recent guideline-recommended approach 1

Severe Renal Impairment (Not on Dialysis)

• For patients with severe renal impairment, doses of 3.0-5.0 mg/kg IV every 24-36 hours are suggested by the National Kidney Foundation 1
• Maintenance doses must be individually adjusted according to creatinine clearance to prevent both underdosing and nephrotoxicity 1, 2

Renal Replacement Therapy Dosing

Continuous Renal Replacement Therapy (CRRT)

• Give standard loading dose of 9 million IU, then maintenance dose of 3 million IU (≈100 mg CBA) every 8 hours 1
• Do not reduce the dose for CRRT—patients require at least 9 million IU per day to maintain therapeutic efficacy 1, 2
• A common pitfall is underdosing CRRT patients; full dosing is essential to achieve adequate plasma levels 1

Intermittent Hemodialysis (IHD)

• Provide standard loading dose of 9 million IU, followed by 2 million IU every 12 hours 1
• Alternatively, 3.0-5.0 mg/kg IV every 24 hours is recommended by Clinical Infectious Diseases society 1
• Schedule dialysis toward the end of the colistin dosing interval to minimize drug removal 1

Critical Monitoring Requirements

• Monitor renal function at baseline and 2-3 times per week during treatment 1
• Acute kidney injury during colistin therapy is a major determinant of clinical failure and mortality 1, 2
• Most colistin-associated nephrotoxicity is dose-dependent and reversible within one week 3
• Failure to adjust maintenance doses for renal function markedly increases the risk of nephrotoxicity 1

Dosing Conversions (Essential to Avoid Errors)

• 1 million IU of colistimethate sodium = 80 mg CMS = 33 mg colistin base activity (CBA) 1, 2
• Accurate conversion is essential to avoid 2-3 fold dosing errors 1
• Colistin is administered as colistimethate sodium (CMS), an inactive prodrug that converts to active colistin 1, 2

Combination Therapy Considerations

• Avoid colistin monotherapy for serious infections—combine with a carbapenem or another active agent to improve clinical outcomes 1
• If no susceptible companion drug is available, combine colistin with a nonsusceptible agent that has the lowest minimum inhibitory concentration 1
• Combination therapy is particularly important when the pathogen MIC is ≥1 mg/L, as recommended doses may be inadequate for these organisms 1

Alternative Agent in AKI: Polymyxin B

• Polymyxin B may be preferred in AKI as it requires no dose adjustment during CRRT and has lower nephrotoxicity (11.8% vs 39.3% with colistin) 3
• For polymyxin B: loading dose of 2-2.5 mg/kg regardless of renal function, maintenance dose of 1.5-3 mg/kg/day with no adjustment needed for CRRT 3
• Polymyxin B is administered as the active drug with plasma concentrations not influenced by renal function 3

Common Pitfalls to Avoid

• Never skip the loading dose in AKI patients—this is the most critical error leading to treatment failure 1
• Do not underdose patients on CRRT—they require full maintenance doses of at least 9 million IU/day 1, 2
• Avoid using colistin as monotherapy—combination therapy improves outcomes and reduces resistance selection 1
• Recognize that patients with creatinine clearance ≥80 mL/min may not achieve target concentrations even with maximum doses, necessitating combination therapy 4