What is the recommended dose of Colistin (polymyxin E) for a patient with normal renal function and severe infection, such as ventilator-associated pneumonia or sepsis?

Colistin Dosing for Severe Infections with Normal Renal Function

For patients with normal renal function and severe infections such as ventilator-associated pneumonia or sepsis, administer a loading dose of 9 million IU of colistin followed by a maintenance dose of 9 million IU/day divided into 2-3 doses (equivalent to 4.5 million IU every 12 hours). 1, 2, 3

Loading Dose: Critical First Step

The loading dose is non-negotiable and must be given to all patients regardless of renal function 1, 2, 3:

• Administer 6-9 million IU as a loading dose (9 million IU is preferred for severe infections) 1, 2, 3
• This is equivalent to approximately 5 mg/kg based on ideal body weight 3, 4
• The loading dose is essential because colistin has a relatively long half-life, and without it, therapeutic plasma concentrations are not achieved for 2-3 days, leading to suboptimal treatment during the critical early infection period 1, 2
• Studies in critically ill patients with VAP showed colistin was undetectable in bronchoalveolar lavage at 2 hours after standard dosing without a loading dose 1

Maintenance Dosing

After the loading dose, continue with maintenance therapy 1, 2, 3, 4:

• 9 million IU/day divided into 2-3 doses (most commonly 4.5 million IU every 12 hours) 1, 2, 3
• Alternative weight-based dosing: 2.5-5 mg/kg/day divided into 2-4 doses for patients with normal renal function 3, 4
• For obese patients, calculate dosing based on ideal body weight, not actual body weight 4

Administration Method

Administer as a 4-hour infusion to optimize pharmacokinetic/pharmacodynamic properties 1, 3:

• This extended infusion may allow treatment of infections involving strains with MIC up to 8 mg/L 1
• The FDA label also describes direct intermittent administration over 3-5 minutes or continuous infusion options, but the 4-hour infusion is preferred based on PK/PD optimization 1, 4

Critical Dosing Conversions

Understanding colistin dosing units is essential to avoid medication errors 1, 2, 3:

• 1 million IU of colistin = 80 mg of colistimethate sodium (CMS) 1, 2, 3
• Colistin is administered as the inactive prodrug CMS, which converts to active colistin in vivo 1, 2, 3
• The 150 mg vial should be reconstituted with 2 mL Sterile Water for Injection to provide 75 mg/mL colistin base activity 4

Monitoring Requirements

Close monitoring of renal function is mandatory 2, 3:

• Check renal function at baseline and 2-3 times per week during treatment 2
• Acute kidney injury during colistin treatment is a major factor related to clinical failure and mortality 2, 5, 3
• Nephrotoxicity is dose-dependent but usually reversible within one week after discontinuation 5
• Research shows nephrotoxicity rates of 27-39% with colistin, with higher rates in patients with advanced age or high SOFA scores 6

Common Pitfalls to Avoid

Failure to give a loading dose is the most critical error 1, 2, 7:

• Approximately one-third to half of patients in clinical practice do not receive a loading dose 7
• Studies demonstrate that patients receiving a loading dose have significantly better clinical outcomes (55.2% vs 35.8% favorable outcomes at day 14) and microbiological eradication rates (50% vs 27.3%) compared to those without 7
• The loading dose does not significantly increase nephrotoxicity risk in patients with normal renal function 7

Inadequate dosing for pathogens with higher MICs 8:

• Standard dosing achieves >90% probability of target attainment only for MIC ≤0.5 μg/mL 8
• For MIC ≥1 μg/mL, standard dosing poses a risk of subtherapeutic exposure 8
• Consider combination therapy for organisms with MIC ≥1 mg/L, as colistin monotherapy may be insufficient 9

Alternative: Polymyxin B

Consider polymyxin B as an alternative, particularly in patients at high risk for renal dysfunction 5:

• Polymyxin B has significantly lower nephrotoxicity (11.8% vs 39.3% with colistin) 5
• Loading dose: 2-2.5 mg/kg; maintenance: 1.5-3 mg/kg/day in 2 doses 1, 5
• Unlike colistin, polymyxin B is administered as the active drug and plasma concentrations are not influenced by renal function 1, 5
• No dose adjustment needed for continuous renal replacement therapy 1, 5