What is the recommended intravenous colistin dosing regimen, duration, and monitoring for an adult with a multidrug‑resistant gram‑negative infection and impaired renal function?

Intravenous Colistin Dosing for Multidrug-Resistant Gram-Negative Infections in Adults with Renal Impairment

All patients, regardless of renal function, must receive a loading dose of 9 million IU (5 mg/kg colistin base activity) intravenously, followed by maintenance dosing calculated using the formula: 2.5 mg CBA × (1.5 × creatinine clearance + 30) mg every 12 hours, with renal function monitored 2-3 times weekly due to significant nephrotoxicity risk. 1

Loading Dose (Universal - No Adjustment for Renal Function)

• Administer 9 million IU (≈5 mg/kg CBA) intravenously to every patient regardless of renal impairment status 1, 2
• The loading dose is critical because omitting it results in subtherapeutic plasma concentrations for 48-72 hours, increasing treatment failure risk 1
• Never reduce or skip the loading dose in renal impairment—this is a common and dangerous error 1

Maintenance Dosing Based on Renal Function

Patients with Mild-to-Moderate Renal Impairment (Not on RRT)

• Use the formula-based approach: Maintenance dose (mg CBA) = 2.5 × (1.5 × creatinine clearance [mL/min] + 30), administered every 12 hours 1
• Alternative simplified approach: For creatinine clearance 10-50 mL/min, give 2-3 million IU every 12-24 hours 1
• For severe renal impairment (CrCl <10 mL/min not on dialysis): 3.0-5.0 mg/kg IV every 24-36 hours 1

Patients on Continuous Renal Replacement Therapy (CRRT)

• Give standard loading dose of 9 million IU, then maintenance of 3 million IU every 8 hours (total 9 million IU/day) 1, 2
• Do not reduce the dose for CRRT—full dosing is required because CRRT significantly removes colistin 1, 3
• Critical pitfall: Many clinicians inappropriately reduce doses in CRRT patients, leading to treatment failure 3

Patients on Intermittent Hemodialysis

• Standard loading dose of 9 million IU, followed by 2 million IU every 12 hours 1, 2
• Schedule dialysis toward the end of the colistin dosing interval to minimize drug removal 1
• Alternative dosing: 3.0-5.0 mg/kg IV every 24 hours 1

Patients with Augmented Renal Clearance (Critically Ill with CrCl >130 mL/min)

• For severe sepsis/septic shock with CrCl >50 mL/min: 4.5 million IU every 12 hours after standard loading dose 1
• Higher doses are needed because augmented clearance rapidly eliminates colistin 4

Duration of Therapy

• Typical duration: 14-21 days for most serious infections 5, 6
• Median duration in clinical studies: 16.5-20 days 5, 6
• Duration should be guided by clinical response, source control, and microbiological clearance 2

Mandatory Monitoring Requirements

Renal Function Monitoring

• Monitor serum creatinine at baseline and 2-3 times per week during therapy 1, 7
• Nephrotoxicity occurs in approximately 36% of critically ill patients (2.4-fold increased risk vs. β-lactams) 7
• Acute kidney injury during colistin therapy is a major predictor of treatment failure and mortality 1, 7

Risk Factors for Nephrotoxicity

• Pre-existing renal impairment, older age, concomitant nephrotoxic medications (especially aminoglycosides), shock states, and prolonged therapy duration 8, 7
• Despite these risks, nephrotoxicity in observational studies ranged from 8-10.9% when carefully monitored 5, 6

Critical Dosing Conversions

• 1 million IU colistimethate sodium = 80 mg CMS = 33 mg colistin base activity (CBA) 1
• Accurate conversion is essential to avoid 2-3-fold dosing errors 1
• Colistin is administered as the inactive prodrug colistimethate sodium (CMS), which converts to active colistin in vivo 2, 9

Combination Therapy Recommendations

• Never use colistin monotherapy for serious infections—combine with at least one additional agent (carbapenem, aminoglycoside, tigecycline, or sulbactam based on susceptibility) 1, 8
• For carbapenem-resistant Acinetobacter baumannii: colistin-carbapenem combinations show highest success rates (SUCRA 83.6%) 8
• If no susceptible companion drug exists, combine with the agent having the lowest MIC even if formally resistant 1
• Evidence for combination therapy superiority remains weak, but clinical practice strongly favors it to prevent resistance and improve outcomes 2, 8

Administration Method

• Administer as a 4-hour infusion to optimize pharmacokinetic/pharmacodynamic properties 2
• Extended infusion may improve tissue penetration and reduce peak-related toxicity 2

Alternative Considerations

When to Prefer Sulbactam Over Colistin

• For Acinetobacter baumannii with sulbactam MIC ≤4 mg/L: use ampicillin-sulbactam (9-12 g/day in 3-4 divided doses) instead of colistin 2, 8
• Sulbactam demonstrates comparable efficacy with significantly lower nephrotoxicity (15.3% vs. 33% with colistin) 2
• This preserves colistin for organisms without alternatives 2

When to Consider Polymyxin B

• Polymyxin B shows significantly lower nephrotoxicity than colistin (11.8% vs. 39.3%) 7
• Polymyxin B requires no dose adjustment during CRRT, simplifying management 2, 7
• Dosing: 2-2.5 mg/kg loading dose, then 1.5-3 mg/kg/day in 2 divided doses 2

Common Pitfalls to Avoid

1. Omitting the loading dose in renal impairment—this guarantees subtherapeutic levels for 2-3 days 1
2. Reducing maintenance doses excessively in CRRT—these patients need full dosing (9 million IU/day minimum) 1, 3
3. Using colistin monotherapy—combination therapy is standard of care for serious infections 1, 8
4. Underdosing to avoid nephrotoxicity—subtherapeutic levels cause treatment failure while still carrying nephrotoxic risk 7
5. Failing to monitor renal function closely—nephrotoxicity is common and predicts mortality 1, 7