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 like ventilator-associated pneumonia or sepsis, administer a loading dose of 9 million IU of colistin followed by a maintenance dose of 4.5 million IU every 12 hours (total 9 million IU/day). 1, 2

Loading Dose Administration

• All patients require a loading dose of 6-9 million IU regardless of renal function to rapidly achieve therapeutic colistin levels 1, 3, 2
• The loading dose is critical because colistin has a relatively long half-life compared to dosing intervals, and without it, plasma concentrations remain suboptimal for 2-3 days before reaching steady state 1, 2
• The FDA-approved dosing range is 2.5-5 mg/kg per day divided into 2-4 doses, but recent evidence supports higher dosing with a loading dose approach 4

Maintenance Dosing

• For normal renal function: 4.5 million IU every 12 hours (9 million IU/day total) 1, 3, 2
• Alternative weight-based dosing: 2.5-5 mg/kg/day divided into 2-4 doses 2, 4
• Administer as a 4-hour infusion to optimize pharmacokinetic/pharmacodynamic properties and potentially treat strains with MIC up to 8 mg/L 1, 2

Critical Dosing Conversions

• Colistin is administered as colistimethate sodium (CMS), an inactive prodrug 1, 2
• 1 million IU of colistin = 80 mg of CMS 1, 3
• This conversion is essential to avoid dosing errors, as multiple reporting systems exist 1

Administration Methods

Intravenous options include: 4

• Direct intermittent: Inject one-half of total daily dose over 3-5 minutes every 12 hours
• Continuous infusion: Inject first half over 3-5 minutes, then infuse remaining half over 22-23 hours

Common Pitfalls and Monitoring

Suboptimal Dosing Risk

• Studies demonstrate that standard CMS administration without a loading dose leads to suboptimal plasma concentrations and is associated with higher mortality 1
• In one study, colistin was undetectable in bronchoalveolar lavage 2 hours after infusion when dosed at 2 million IU every 8 hours 1
• Real-world data shows that 43% of patients receive doses not following current recommendations, particularly those with renal impairment 5

Nephrotoxicity Considerations

• Monitor renal function closely at baseline and 2-3 times per week during treatment 3
• Acute kidney injury during colistin treatment is a major factor related to clinical failure and mortality 3, 6
• Nephrotoxicity rates range from 27-35% without loading dose to potentially 69% with loading dose in patients with SOFA score >7 7
• Age is a significant risk factor for nephrotoxicity, with older patients (median 67 vs 50 years) at higher risk 7
• Most nephrotoxicity is reversible within one week of discontinuation 6

Loading Dose Efficacy Evidence

• A multicenter study showed that loading dose administration resulted in higher favorable clinical outcomes (55.2% vs 35.8%) and microbiological eradication rates (50% vs 27.3%) at day 14 compared to no loading dose 8
• The loading dose group had shorter hospital stays without increased nephrotoxicity risk 8

Alternative Consideration: Polymyxin B

Polymyxin B may be preferred in certain situations: 1, 6

• Loading dose: 2-2.5 mg/kg; Maintenance: 1.5-3 mg/kg/day in 2 doses 1
• Does not require dose adjustment in renal replacement therapy 1, 6
• Lower incidence of nephrotoxicity (11.8% vs 39.3% with colistin) 6
• Administered as active drug, not a prodrug, so plasma concentrations are not influenced by renal function 1