Pharmacokinetics of colistin in adult critically ill patients in South Africa

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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.

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