The significance of different formulations of aerosolized colistin

Abstract

We thank Dr Mubareka and Dr Rubinstein for their thoughtful commentary [1] related to our recent publication on aerosolized colistin for the treatment of nosocomial pneumonia due to multidrug-resistant Gram-negative bacteria in patients without cystic fibrosis [2]. We would like to provide some additional clarifications related to the formulation of colistin used in our study because the commentators state that ... it is not clear why the more toxic form of colistin was chosen over the better-tolerated colistin sulphamethate. There are two different forms of colistin available for clinical use. Colistin sulfate is administered orally for bowel decontamination and is administered topically as a powder for the treatment of bacterial skin infections; and colistimethate sodium (also called colistin methanesulfate, pentasodium colistimethanesulfate, colistin sulfamethate, and colistin sulfonyl methate) is administered intravenously and intramuscularly [3]. It is obvious that the terminology regarding the different formulations of colistin may be confusing. Colistimethate sodium is produced by a sulfomethylation reaction of colistin in which the primary amine groups of L-α-γ-diaminobutyric acid are reacted with formaldehyde followed by sodium bisulfite [4]. Both formulations of colistin (colistin sulfate and colistimethate sodium) have been used for aerosol treatment. However, colistimethate sodium is associated with fewer adverse effects such as chest tightness, throat irritation, and cough compared with colistin sulfate [5]. The formulation of colistin that was administered to our patients was therefore colistimethate sodium (i.e. the less toxic form of the drug), not colistin sulfate. In fact, the exact trade names of colistin that were administered to our patients are stated in our paper [2].