Colistin exposure, therapeutic target attainment, and renal safety in critically ill older adults: A prospective observational study.

BACKGROUND

The rise of multidrug-resistant Gram-negative bacteria has made polymyxins vital last-line therapies. However, its pharmacokinetics in elderly patients remain poorly characterized, which hinders dosing optimization to balance efficacy and toxicity risks in this vulnerable population.

METHODS

A prospective, single-centre observational study was conducted in elderly (≥65) intensive care unit (ICU) patients who received colistin sulfate therapy. Blood samples were collected prior and post-dose time points. Plasma concentrations of colistin sulfate were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic (PK) parameters were calculated via non-compartmental analysis. Treatment-emergent adverse events and laboratory parameters were systematically recorded for safety evaluation.

RESULTS

Thirteen patients with MDR gram-negative infections were included and all received colistin sulfate-based combination therapy; 84.6% achieved anti-infective efficacy. Compared with previously reported data in healthy individuals at 50 MIU q12h, elderly patients demonstrated significantly higher AUC0-12h (9.62 ± 3.58 vs. 5.33 ± 0.71 mg·h/L, p < 0.05), prolonged T1/2 (25.84 ± 25.19 vs. 4.53 ± 1.22 h, p < 0.05), and larger Vd (87.57 ± 74.40 vs. 17.32 ± 2.52 L, p < 0.05). Target attainment(AUC0-24h/MIC ≥ 50) probability was ≥ 80% only at MIC ≤ 0.25 mg/L, dropping to ≤ 20% at MIC ≥ 0.5 mg/L. Serum creatinine elevations occurred during colistin therapy and returned to baseline after discontinuation 7-14 days, while liver function parameters remained stable throughout.

CONCLUSIONS

Colistin sulfate therapy in critically ill elderly ICU patients demonstrates elevated systemic exposure with reversible nephrotoxicity, necessitating pharmacokinetic-guided dosing strategies individualized to renal function, therapeutic drug monitoring, and clinical severity.