Abstract Objectives To determine the PK of the pro-drug colistimethate sodium (CMS) and colistin in adult patients admitted to a South African critical care unit and to compare the PK with historical data. Materials and methods We conducted a prospective, observational, PK study in critically ill adult patients receiving intravenous colistin as part of standard of care. CMS was administered as a loading dose of either 9 million units (MU) or 12 MU followed by maintenance doses dependent on creatinine clearance (CrCl) at either 12- or 8-hourly. PK samples were collected at 1, 2, 4, 8, 12, 24 and 48 hours post-loading dose. CMS and colistin concentrations were analysed using liquid chromatography–tandem mass spectrometry. The PK of CMS and colistin were described using non-compartmental analysis in Phoenix WinNonlin. Results We enrolled 24 participants, 50% (12/24) were admitted with burns. Mean age was 42 years (SD ± 16.3) and mean CrCl was 140 mL/min (SD ± 58.7). The PK parameters following a loading dose of 9 MU were comparable to published data. Colistin AUC showed a negative correlation with white cell count (r = −0.63) and eGFR (r = −0.44). Probability of target attainment was acceptable at Acinetobacter baumannii minimum inhibitory concentrations 1 mg/L. Conclusion Our results are comparable to previously published literature. Notably, increasing eGFR and WCC decreased colistin AUC. Future work will adopt a population pharmacokinetic modelling approach to quantify and account for sources of variability, with the aim of informing individualized dosing strategies for this South African population.
Lorente et al. (Tue,) studied this question.