What is the recommended dose of colistin (injection colistin) for a patient with suspected or confirmed multi-drug resistant gram-negative bacterial infection and potentially impaired renal function?

Colistin Injection Dosing

For critically ill adults with multidrug-resistant gram-negative infections, administer a loading dose of 9 million IU (300 mg colistin base activity) followed by maintenance dosing of 4.5 million IU every 12 hours, adjusted for renal function. 1

Standard Adult Dosing Regimen

Loading Dose (Critical - Never Skip)

• Always give 9 million IU (300 mg CBA) as a loading dose regardless of renal function 1, 2
• This loading dose is essential because colistin takes 2-3 days to reach steady-state concentrations without it, leaving patients with subtherapeutic levels during the critical early infection period 1
• Administer over 3-5 minutes as direct intravenous injection 3

Maintenance Dosing for Normal Renal Function

• 4.5 million IU every 12 hours for patients with creatinine clearance >50 mL/min 1
• This translates to 2.5-5 mg/kg/day of colistin base activity divided into 2-4 doses per the FDA label 3
• The higher end of dosing (closer to 5 mg/kg/day) correlates with better microbiological outcomes 4

Dose Adjustment for Renal Impairment

Adjust only the maintenance dose (never reduce the loading dose): 1, 2

• CrCl 50-79 mL/min: 2.5-3.8 mg/kg divided into 2 doses daily 3
• CrCl 30-49 mL/min: 2.5 mg/kg once daily or divided into 2 doses 3
• CrCl 10-29 mL/min: 1.5 mg/kg every 36 hours 3

Continuous Renal Replacement Therapy (CRRT)

• At least 9 million IU per day during CRRT 1
• No consensus exists on exact dosing, but do not reduce doses excessively as colistin is partially removed by CRRT 1

Intermittent Hemodialysis

• 2 million IU every 12 hours with normal loading dose 1
• Schedule dialysis toward the end of the dosing interval 1

Administration Methods

Direct Intermittent Administration

• Inject one-half of total daily dose over 3-5 minutes every 12 hours 3

Continuous Infusion (Alternative)

• Inject one-half of total daily dose over 3-5 minutes initially 3
• Add remaining half to compatible IV solution (0.9% NaCl, D5W, lactated Ringer's, etc.) 3
• Infuse over 22-23 hours starting 1-2 hours after initial dose 3

Critical Dosing Pitfalls to Avoid

Never Underdose to Prevent Nephrotoxicity

• Subtherapeutic colistin levels lead to treatment failure and increased mortality while still carrying nephrotoxic risk 2
• Higher doses (median 2.9 mg/kg/day) independently predict microbiological success compared to lower doses (1.5 mg/kg/day) 4
• Patients receiving higher doses had significantly better 7-day survival 4

Obesity Considerations

• Base dosing on ideal body weight, not actual body weight 3

Augmented Renal Clearance

• Critically ill patients, burn patients, and those with high creatinine clearance may require doses exceeding standard recommendations 5
• Therapeutic drug monitoring should be considered in these populations 5

Mandatory Monitoring Requirements

Renal Function Surveillance

• Monitor renal function 2-3 times per week during therapy 2
• Nephrotoxicity occurs in approximately 36% of critically ill patients 2
• Acute kidney injury is a major factor related to clinical failure and mortality 1

Risk Factors for Nephrotoxicity

• Pre-existing chronic kidney disease 6
• Diabetes mellitus 6
• Concurrent aminoglycoside use (avoid if possible) 6
• Elderly patients 1

Combination Therapy Recommendations

Colistin should be used in combination with one or more additional agents to which the pathogen displays in vitro susceptibility 1

When No Susceptible Agent Available

• Combine with a second or third non-susceptible agent (e.g., carbapenem) with the lowest MIC 1
• Colistin-carbapenem combinations show superior outcomes (SUCRA 83.6%) compared to monotherapy 1

Evidence on Combination vs. Monotherapy

• The evidence is controversial and mixed 1
• One RCT showed no difference between colistin-meropenem combination vs. monotherapy 1
• However, observational data suggests combination therapy may reduce mortality 1

Pediatric Dosing

Standard Pediatric Dose

• Loading dose: 0.15 MU/kg (equivalent to 5 mg CBA/kg) 7
• Maintenance: 0.075 MU/kg every 12 hours (2.5-5 mg CBA/kg/day) 1, 7

Important Pediatric Considerations

• FDA/EMA-recommended doses may be inadequate when pathogen MIC ≥1 mg/L 1, 7
• Higher doses needed for augmented renal clearance 1, 7
• Nephrotoxicity risk is 5.8-19% in pediatric populations 7

Alternative: Polymyxin B

Polymyxin B demonstrates significantly lower nephrotoxicity (11.8% vs. 39.3% with colistin) and may be preferred 2

Polymyxin B Dosing

• Loading dose: 2-2.5 mg/kg 1
• Maintenance: 1.5-3 mg/kg/day 1
• No dose adjustment needed for CRRT 1, 2
• Dosing based on actual body weight, not affected by renal function 1

Expected Clinical Outcomes

Efficacy Data

• Clinical response (cure or improvement): 66.7-82.1% 8, 9
• Microbiological success: 68% at day 7 4
• Overall mortality: 24-26.7% 8, 10

Safety Profile

• Nephrotoxicity: 8-17.8% in most studies 8, 9, 10
• Most nephrotoxicity is reversible and does not require renal replacement therapy 9