Optimizing Colistin Sulfate Dosing in Severe Infections: A Population Pharmacokinetic Model-Guided Approach
Yingchao Ma1, Yongjing Wang1, Xia Wu1
1Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People's Republic of China.
Drug Design, Development and Therapy
|June 22, 2026
Summary
Individualized dosing of colistin sulfate is crucial for critically ill patients with carbapenem-resistant Gram-negative bacilli infections. Renal function significantly impacts colistin clearance, necessitating dose adjustments for optimal treatment outcomes.
Area of Science:
- Pharmacokinetics and Pharmacodynamics
- Infectious Diseases
- Critical Care Medicine
Background:
- Colistin sulfate is vital against carbapenem-resistant Gram-negative bacilli but has a narrow therapeutic window and high resistance risk.
- Limited clinical data and high pharmacokinetic variability necessitate individualized dosing strategies.
- Optimizing colistin sulfate dosing is critical for critically ill patients.
Purpose of the Study:
- To develop a population pharmacokinetic (PPK) model for colistin sulfate.
- To optimize and guide precise individualized dosing in critically ill patients.
- To improve clinical efficacy and minimize resistance risk.
Main Methods:
- A PPK model was developed using NONMEM in critically ill patients with confirmed CRO infections.
- Model performance was evaluated using goodness-of-fit diagnostics and visual predictive checks.
- Monte Carlo simulations determined the probability of target attainment (PTA) for various dosing regimens and MICs.
Main Results:
- The PPK model identified creatinine clearance (CrCL) as a significant covariate affecting colistin clearance.
- Standard dosing achieved PTA ≥90% only when MIC ≤0.5 μg/mL with normal renal function.
- Insufficient exposure was noted with MIC ≥1 μg/mL in patients with normal renal function, and no regimen achieved PTA ≥90% for MIC ≥2 μg/mL.
Conclusions:
- Renal function significantly impacts colistin sulfate clearance, requiring dose adjustments based on CrCL.
- Standard dosing may lead to underexposure in patients with normal renal function and higher MICs.
- Consideration of off-label high-dose regimens is recommended for such cases to ensure adequate drug exposure.
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