PI-060 - CHARACTERIZING COLISTIN PHARMACOKINETICS FOLLOWING A LOADING DOSE: FIRST DESCRIPTION IN AN AFRICAN COHORT.

V. Pillay-Fuentes Lorente¹, A. Abulfathi², J. de Jong¹, K. Reddy³, R. van Rensburg¹, U. Lalla⁴, R. Davids⁵, A. Parker⁶, T. Lovelock⁶, T. kellermann¹, E. Decloedt¹; ¹Division of Clinical Pharmacology, Department of Medicine, Stellenbosch University, Cape Town, South Africa, ²Certara USA, Norristown, PA, USA, ³Microbiology Department, National Health Laboratory Service, South Africa, Microbiology Department, National Health Laboratory Service, South Africa, ⁴Division of Pulmonology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa, ⁵Department of Anaesthesiology and Critical Care, Stellenbosch University, Cape Town, South Africa, ⁶Division of Infectious Diseases, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Background:

Background: Colistin, an old but effective low-cost antimicrobial, still remains widely used in low-to-middle income countries to treat multidrug resistant gram-negative bacterial (MDR-GNB) infections. However, colistin pharmacokinetic (PK) data are limited, with no data on African patients. Average steady state plasma concentration of 2 mg/L is associated with efficacy. Our objective was to determine the PK of colistin after administration of a loading dose in South African patients.

Methods:

Methods: We conducted a prospective, observational, PK study in critically-ill adult patients receiving intravenous colistin as part of standard of care. Colistin was administered as a loading dose of 9 million units colistimethate sodium, equivalent to 300 mg colistin base activity. PK samples were collected at 1, 2, 4, 8, 12, 24 and 48-hours post-loading dose. Colistin concentrations were analyzed using liquid chromatography-tandem mass spectrometry. The PK of colistin were described using non-compartmental analysis in Phoenix WinNonlin.

Results:

Results: We enrolled 22 participants, 73% (16/22) males and 55% (12/22) were admitted with burns. Median age was 44 years (interquartile range [IQR] 26 - 51) and median creatinine clearance was 140 mL/min (IQR 103 - 186). Geometric mean area-under-the-concentration-time curve over 12 hours (AUC0-12) was 27.1 mg.h/L (percent co-efficient of variation [CV], 50%). Geometric mean of the average concentration over the first dosing interval was 2.3 mg/L (CV 50%) with 32% (7/22) < 2 mg/L.

Conclusion:

Conclusion: Our results are comparable to published data in non-African populations. Notably, in one-third of patients average plasma colistin concentrations were below the target concentrations. Our future work will adopt a population modelling approach to quantify and account for the sources of variability to inform individualized dosing strategies in South Africans.