Pharmacokinetics of colistin in patients with multidrug-resistant Gram-negative infections: A pilot study

BACKGROUND & OBJECTIVES: There is little information concerning intravenously (i.v.) administered colistin in patients with multidrug-resistant (MDR) Gram-negative infections. Thus, this pilot prospective study was undertaken to characterize efficacy and pharmacokinetics of colistin in patients with MDR Gram-negative infections. METHODS: Nine patients with age >12 yr and MDR Gram-negative infections were included, of whom six were given colistin at the doses of 2 MU, while three patients were given 1 MU i.v. dose every 8 h. Blood samples were collected at different time intervals. Determination of colistin concentration was done by a ultra-high-performance liquid chromatography/mass spectrometry/selected reaction monitoring assay. RESULTS: The area under the plasma concentration-versus-time curve over eight hours (AUC(0-8)) for colistin after the 1(st) dose ranged from 3.3 to 16.4 mg×h/l (median, 4.59). After the 5(th) dose, AUC(0-8) for colistin ranged from 4.4 to 15.8 mg×h/l (median, 6.0). With minimal inhibitory concentration (MIC) value of 0.125 mg/l, AUC(0-8)/MIC ranged from 26.7 to 131.4 (median, 36.7) and 35.5 to 126.0 (median, 48.0) after the 1(st) and the 5(th) doses of 2 MU every 8 h, respectively. INTERPRETATION & CONCLUSIONS: As there is a paucity of information on AUC/MIC for colistin, it may not be possible to conclude whether AUC/MIC values in our patients were adequate. There is a microbiological clearance of organism, which goes in favour of the dosing schedule being adequate. Further studies need to be done to understand the pharmacokinetics of colistin in patients with infections.