Colistin: how should it be dosed for the critically ill?

Area of Science:

• Pharmacology
• Infectious Diseases
• Critical Care Medicine

Background:

• Colistin is a last-resort antibiotic for multidrug-resistant Gram-negative bacterial infections.
• Colistin is administered as an inactive prodrug, colistin methanesulfonate (CMS).
• Optimal colistin dosing is critical due to its narrow therapeutic window.

Purpose of the Study:

• To review advances in optimizing colistin dosing in critically ill patients.
• To provide scientifically based recommendations for colistin administration.
• To address dose adjustments for renal impairment and renal replacement therapy.

Main Methods:

• Development of a dosing algorithm for achieving target plasma colistin concentrations.
• Consideration of loading doses for rapid achievement of therapeutic levels.
• Review of therapeutic drug monitoring and combination therapy strategies.

Main Results:

• Dosing algorithms account for renal function and renal replacement therapy.
• Loading doses are necessary for timely effective concentrations.
• Inhalation or direct CNS administration of CMS enhances local colistin concentrations.

Conclusions:

• Optimized colistin dosing strategies improve clinical outcomes.
• Therapeutic drug monitoring is essential due to high interpatient variability.
• Alternative administration routes (inhalation, intrathecal) enhance efficacy and minimize systemic toxicity.