title: CSA-131, a ceragenin active against colistin-resistant Acinetobacter baumannii and Pseudomonas aeruginosa clinical isolates.
abstract: 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. MIC(50) and MIC(90) values were determined using 15 epidemiologically unrelated A. baumannii and P. aeruginosa strains, with MIC(50) and MIC(90) 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.
authors.affiliation: ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain; Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Vila-Farrés
authors.affiliation: ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.
authors.forename: Anna Elena
authors.initials: AE
authors.lastname: Callarisa
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Savage
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain; Department of Organic Chemistry, University of Barcelona, Barcelona, Spain.
authors.forename: Ernest
authors.initials: E
authors.lastname: Giralt
authors.affiliation: ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain; Department of Clinical Microbiology, CDB, Hospital Clinic, School of Medicine, University of Barcelona, Barcelona, Spain. Electronic address: jvila@ub.edu.
authors.forename: Jordi
authors.initials: J
authors.lastname: Vila
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003091:Colistin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013256:Steroids / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D013256:Steroids; D003091:Colistin
keywords: Acinetobacter baumannii; Activity; Ceragenins; Pseudomonas aeruginosa