Critically-ill patients with acute kidney injury could benefit from higher doses of the antibiotic colistin on the days they are also receiving dialysis, according to a new study by Monash University and Mahidol University.
Colistin is a treatment for life-threatening multidrug-resistant Gram-negative infections, such as pneumonia and bloodstream infections, against which other antibiotics fail. It is administered intravenously as the inactive prodrug colistin methanesulfonate (CMS), which is converted in the body to the active colistin.
Led by the Monash Institute of Pharmaceutical Sciences (MIPS) and Mahidol University (Bangkok, Thailand), the researchers evaluated CMS and colistin concentrations among 13 critically-ill patients being treated with the antibiotic and also receiving sustained low-efficiency dialysis (SLED) – a commonly used type of dialysis for kidney replacement therapy in very sick patients. SLED is run over several hours on days when kidney support is required.
The goal was to determine how SLED impacts the time-courses of CMS and colistin concentrations and, ultimately, provide infectious disease clinicians and patients with clinically applicable dosing regimens to maximise the probability of successful treatment outcome.
Published in Clinical Microbiology and Infection, the researchers characterised the population pharmacokinetics (concentration and time-course of drug exposure) of CMS and colistin following administration of CMS to each patient on SLED days and non-SLED days.
Blood and urine samples were collected on both SLED and non-SLED days, followed by measurement of CMS and colistin concentrations and the development of a population pharmacokinetic model.
Results showed the rates at which CMS and colistin are eliminated from the body were substantially higher during SLED and, therefore, a higher dose of CMS should be administered on days when SLED is undertaken. Simulations using the developed population pharmacokinetic model evaluated likely benefits versus risks of different dosing regimens.
The study's corresponding author, Associate Professor Cornelia Landersdorfer from MIPS, said the team hopes the findings fill a gap in knowledge relating to dosing regimens for high-risk patients being treated with CMS and requiring SLED.
"This study is the first to examine CMS and colistin disposition exclusively in patients undergoing SLED by applying population pharmacokinetic modeling, and enrolled 13 patients, making it an important development for clinicians and patients alike," Associate Professor Landersdorfer said.
MIPS PhD candidate Dominika Fuhs was a lead author of the study.
"Our findings generated clinically applicable dosing regimens, showing that CMS doses should be higher on days when SLED is undertaken due to the greater rate at which CMS and colistin exit the body on those days," Ms Fuhs said.
Dr Adhiratha Boonyasiri from Mahidol University, was also a lead author who specialises in infectious disease epidemiology. "There is currently very little information on the handling of CMS and colistin in critically-ill patients on days when SLED is undertaken, so we are excited to publish our findings and contribute to enhancing dosing regimens for such patients," Dr Boonyasiri said.
The next step is for the developed dosing regimens to be applied clinically.
The full study, titled Disposition of colistin in critically-ill patients on sustained low-efficiency dialysis: a population pharmacokinetic study can be found here: https://www.sciencedirect.com/science/article/pii/S1198743X25002526
DOI: https://doi.org/10.1016/j.cmi.2025.05.021
