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 (AUC0-8) for colistin after the 1st dose ranged from 3.3 to 16.4 mg×h/l (median, 4.59). After the 5th dose, AUC0-8for 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, AUC0-8/MIC ranged from 26.7 to 131.4 (median, 36.7) and 35.5 to 126.0 (median, 48.0) after the 1st and the 5th 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.
Keywords: Colistin - Gram-negative infections - MDR - pharmacodynamics - pharmacokinetics.