The Activity of Polymyxins against Dense Populations of Escherichia coli

Abstract

The activities of polymyxin B sulfate, colistin (polymyxin E) sulfate and their sulfomethyl derivatives were compared by continuous turbidimetric monitoring of dense cultures of an E. coli strain exposed to these agents. Judged by the concentration of antibiotic which caused a rapid fall in opacity of the culture, polymyxin B sulfate and colistin sulfate had similar activities, but the sulfomethyl compounds differed considerably: sulfomyxin sodium induced lysis of the culture at a concentration 4 times that of the parent compound and colistin sulfomethate sodium induced a delayed fall in opacity consistent with recruitment of activity as the inactive sulfomethyl derivative was broken down to the parent compound. During overnight incubation, regrowth of cultures which initially succumbed to polymyxin action occurred, apparently due to the selection of phenotypically resistant variants from within the population. In this way cultures could easily be adapted to growth in concentrations of antibiotic well above the conventionally-determined minimum inhibitory concentration. The comparative ease of adaptation was in the order: colistin sulfomethate > sulfomyxin > colistin sulfate > polymyxin B sulfate.