Clinical pharmacokinetics of colistimethate sodium and formed colistin in patients with renal impairment or on dialysis modalities: a systematic review and implications for precision dosing.

BACKGROUND

Optimizing colistin dosing in patients with renal impairment, particularly those undergoing renal replacement therapy (RRT), remains a major challenge due to complex and variable pharmacokinetics. This systematic review identifies key covariates affecting pharmacokinetics of colistimethate sodium (CMS) and its active form colistin and evaluates dosing variability in patients with renal impairment, including those receiving RRT.

METHODS

Systematic searches of PubMed, Embase, Scopus, and Cochrane Library (up to November 2025) identified studies reporting the pharmacokinetics of intravenous CMS, formed colistin or colistin sulfate (nebulized CMS used as adjuvant in some studies) in adults with renal impairment or on RRT. Data on dosing regimens, dialysis characteristics, pharmacokinetic parameters, and covariates were extracted, and methodological quality was appraised using validated pharmacokinetic criteria.

RESULTS

Thirteen studies (n = 450) met inclusion. CMS clearance was primarily determined by renal function and dialysis-related parameters were the most consistent determinants of pharmacokinetics, while additional covariates such as cystatin C, ALT, hematocrit, and body weight were identified in individual studies. In patients undergoing SLEDD, extracorporeal clearance was reported to account for up to 67% of total drug clearance in a single study. Standardized CMS dosing regimens often failed to achieve pharmacodynamic targets for formed colistin (fAUC/MIC ≥12).

CONCLUSIONS

Colistin pharmacokinetics in patients with renal impairment and those receiving renal replacement therapy are highly variable and influenced by both renal and non-renal factors, including dialysis modality. Standard dosing regimens frequently fail to achieve pharmacodynamic targets, highlighting the need for individualized, physiology-based dosing strategies. Integration of renal function, RRT parameters, and emerging biomarkers such as cystatin C, alongside therapeutic drug monitoring, is essential to optimize efficacy while minimizing toxicity in this high-risk population.

PROSPERO: www.crd.york.ac.uk/prospero identifier is CRD42021294141.