Evaluation of methods for determining antibacterial activity of serum and urine after colistimethate injection

The purpose of this study was to evaluate methods for determining antibacterial activity in serum and urine following intramuscular administration of colistimethate sodium to man. The levels of actual antibacterial activity were determined by a serial dilution technique with the use of 30 minutes of incubation, and the results were compared with levels determined by an agar diffusion method and a serial dilution technique with 18 hours of incubation. The results indicate that colistimethate sodium itself has little antibacterial activity but that activation occurs rapidly in vivo. Antibacterial activity in serum was sustained for up to 12 hours after injection of colistimethate sodium. Levels derived with serial dilution methods with 18 hour incubation periods were falsely elevated, and levels obtained from agar diffusion techniques were falsely low. The inaccuracy of the agar diffusion results was, at least in part, related to a decrease in diffusibility of colistimethate sodium that occurs as the material is activated.