The present invention relates to a polymyxin derivative wherein the derivativehas a total of three positive chargesat physiological pH and wherein the terminal moiety (D) of the derivativecomprises a total of 1 to 5 carbon atoms； and to acom-bination product comprising at least two such derivatives. The inventionfurther relates to a method for sensitizing Gram-negativebacteria to an antibacterial agent by administering, simultaneously orsequentially in any order a therapeutically effective amountof said antibacterial agent and a derivative according to the presentinvention to said subject； to methods for developing novelan-tibiotics； and for sensitizing clinically important bacteria to a hostdefense mechanism complement present in serum. Theinven-tion also relates to a method of treating a subject for a gram-negativebacterial infection by administering a polymyxin derivativeof the invention in combination with a second antibacterial agent. Finally,the invention relates to a process for preparing suchpolymyxin derivatives.
