Optimizing colistin dosing in patients undergoing continuous kidney replacement therapy: critical considerations for intensivists

Abstract

[...]polymyxins remain crucial therapeutic options for MDR-GNB infections [5]. The emergence of colistin resistance, first reported in 2015, has been attributed to the plasmid-mediated mobile colistin resistance gene (mcr-1), which encodes phosphoethanolamine transferase, conferring resistance in certain Gram-negative bacteria. The need for higher colistin doses during CKRT may be explained by the extensive carrier-mediated tubular reabsorption of colistin in the kidneys, a physiological mechanism not replicated by extracorporeal devices currently used in clinical practice [10]. [...]in patients with renal failure, plasma concentrations of colistimethate sodium—substantially removed during continuous veno-venous hemodiafiltration (CVVHDF)—are significantly higher than active colistin concentrations due to reduced conversion efficiency [11]. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study.