CSA-131, a ceragenin active against colistin-resistant Acinetobacter baumannii and Pseudomonas aeruginosa clinical isolates

•Good in vitro activity (MIC90 of 2 mg/L) of ceragenin CSA-131 against epidemiologically unrelated Acinetobacter baumannii and Pseudomonas aeruginosa clinical isolates.•Killing curves of CSA-131 showed bactericidal behaviour at all of the concentrations tested, with re-growth at the lowest concentrations both in A. baumannii and P. aeruginosa.•CSA-131 may be a potential future agent to treat infections caused by A. baumannii and P. aeruginosa even when the strain is resistant to colistin.

In the last decade the number of Acinetobacter baumannii and Pseudomonas aeruginosa isolates showing extended drug resistance and pandrug resistance has steadily increased, thereby limiting or eliminating the antibiotics that can be used to treat infections by these micro-organisms. In addition, few antibiotics have been launched in the last decade. The objective of this study was to investigate the in vitro activity of several ceragenins against A. baumannii and P. aeruginosa. Four ceragenins (CSA-138, -13, -131 and -44) were tested both against colistin-susceptible and colistin-resistant A. baumannii and P. aeruginosa clinical isolates using the microdilution method. Time–kill curves of CSA-131 were performed against colistin-resistant A. baumannii and P. aeruginosa strains. The ceragenin CSA-131 showed the best activity against A. baumannii and P. aeruginosa, with minimum inhibitory concentrations (MICs) of 2 mg/L and <0.5 mg/L, respectively. MIC50 and MIC90 values were determined using 15 epidemiologically unrelated A. baumannii and P. aeruginosa strains, with MIC50 and MIC90 values for CSA-131 being 2 mg/L for A. baumannii and 1 mg/L and 2 mg/L, respectively, for P. aeruginosa. The killing curves of CSA-131 showed bactericidal behaviour at all of the concentrations tested, with re-growth at the lowest concentrations both in A. baumannii and P. aeruginosa. The good MICs of CSA-131 both against A. baumannii and P. aeruginosa and its high bactericidal activity may make this ceragenin a potential future agent to treat infections caused by these two pathogens even when the strain is resistant to colistin.