From the Guidelines
Intravenous colistin (polymyxin E) therapy should be administered with a loading dose of 9 MU (5 mg/kg) followed by a maintenance dose of 4.5 MU (2.5 mg) twice daily in critically-ill patients, as recommended by recent guidelines 1.
Administration Guidelines
The administration of colistin requires careful consideration due to its potential toxicity.
- A loading dose of 9 MU (5 mg/kg) of colistin is suggested, followed by a maintenance dose of 4.5 MU (2.5 mg) twice daily in critically-ill patients 1.
- Dosage adjustment is essential for patients with renal impairment, with reductions of 50-75% for those with creatinine clearance below 50 ml/min.
- Administration should occur via slow intravenous infusion over 30-60 minutes to minimize adverse effects.
Precautions
Regular monitoring of renal function is crucial, with serum creatinine and BUN checked at baseline and every 2-3 days during therapy 1.
- Neurotoxicity can occur, manifesting as paresthesias, vertigo, or neuromuscular blockade, requiring vigilant clinical assessment.
- Concurrent nephrotoxic medications should be avoided when possible.
- Adequate hydration must be maintained throughout treatment.
Treatment Duration
Treatment duration typically ranges from 7-14 days depending on infection severity and clinical response, though longer courses may be necessary for complicated infections. The most recent and highest quality study 1 supports the use of colistin as a treatment option for infections due to multidrug-resistant organisms, with a suggested dosage regimen of 9 MU of colistin methanesulfonate (CMS) initially followed by 4.5 MU CMS twice a day as the maintenance dose. However, it is essential to note that the optimal dosage of colistin in pediatric patients remains uncertain, and the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) recommends a loading dose of 0.15 MU/kg of colistin in children followed by a maintenance dose of 0.075 MU/kg every 12 h 1. Additionally, a task force on management and prevention of Acinetobacter baumannii infections in the ICU suggests the use of a loading dose of 6–9 million IU and subsequently high, extended-interval maintenance doses (4.5 million IU/12 h) in critically ill patients and patients with severe sepsis/septic shock with creatinine clearance above 50 mL/min 1.
From the FDA Drug Label
DOSAGE AND ADMINISTRATION ... INTRAVENOUS ADMINISTRATION Direct Intermittent Administration - Slowly inject one-half of the total daily dose over a period of 3 to 5 minutes every 12 hours. Continuous Infusion - Slowly inject one-half of the total daily dose over 3 to 5 minutes Add the remaining half of the total daily dose of Colistimethate for Injection, USP to one of the following: 0.9% NaCI 5% dextrose in 0.9% NaCI 5% dextrose in water 5% dextrose in 0.45% NaCI 5% dextrose in 0. 225% NaCI lactated Ringer's solution 10% invert sugar solution Administer the second half of the total daily dose by slow intravenous infusion, starting 1 to 2 hours after the initial dose, over the next 22 to 23 hours
The administration guidelines for intravenous Colistin (polymyxin E) therapy are as follows:
- Direct Intermittent Administration: slowly inject one-half of the total daily dose over 3 to 5 minutes every 12 hours.
- Continuous Infusion: slowly inject one-half of the total daily dose over 3 to 5 minutes, then add the remaining half to a compatible solution and administer by slow intravenous infusion over 22 to 23 hours.
- Compatible solutions for continuous infusion include:
- 0.9% NaCI
- 5% dextrose in 0.9% NaCI
- 5% dextrose in water
- 5% dextrose in 0.45% NaCI
- 5% dextrose in 0.225% NaCI
- lactated Ringer's solution
- 10% invert sugar solution In the presence of impaired renal function, reduce the infusion rate depending on the degree of renal impairment 2.
From the Research
Administration Guidelines for Intravenous Colistin Therapy
- Colistin is administered as its inactive prodrug colistin methanesulfonate (CMS) in patients, parenterally or by inhalation 3.
- A dosing algorithm has been developed to achieve desired plasma colistin concentrations in critically ill patients, including necessary dose adjustments for patients with impaired kidney function and those on renal replacement therapy 3, 4.
- Due to the slow conversion of CMS to colistin, a loading dose is needed to generate effective concentrations within a reasonable time period 3.
- Therapeutic drug monitoring is warranted, where available, because of the observed high interpatient variability in plasma colistin concentrations 3.
Precautions for Intravenous Colistin Therapy
- The most important concern with polymyxins (Colistin and Polymyxin B) use is nephrotoxicity 5.
- Colistin in currently recommended doses is significantly more nephrotoxic than Polymyxin B, and colistin toxicity is dose-dependent, mostly mild to moderate, and is reversible in most cases 5.
- Nephrotoxicity developed in 39.3% patients in the Colistin group compared to 11.8% patients in the Polymyxin B group 5.
- Colistin adsorption by the haemofilter contributed to its extracorporeal clearance to a large extent, and total colistin clearance was reduced compared with patients with normal renal function 6.
Special Considerations
- For patients receiving renal replacement therapy, supplemental dosing is needed to achieve target attainment rates of >80% for average steady-state plasma colistin concentration (Css,avg) ≥2mg/L 4.
- Inhalation of CMS achieves considerably higher colistin concentrations in lung fluids than is possible with intravenous administration, with negligible plasma exposure 3.
- For central nervous system infections, dosing CMS directly into the cerebrospinal fluid generates significantly higher colistin concentrations at the infection site compared with what can be achieved with systemic administration 3.