title: In vitro activities of the novel ceragenin CSA-13, alone or in combination with colistin, tobramycin, and ciprofloxacin, against Pseudomonas aeruginosa strains isolated from cystic fibrosis patients.
abstract: BACKGROUND
  The rise in the rates of antibiotic resistance among Pseudomonas aeruginosa strains from cystic fibrosis (CF) patients is concerning and underscores the need for the development of novel compounds. Among them CSA-13, a cationic steroid molecule, mimics the activity of naturally occurring antimicrobial peptides.
  
  
  METHODS
  MICs and MBCs were determined using the microbroth dilution technique. Combinations were assessed using the checkerboard technique. The bactericidal activity of CSA-13 in combination with colistin was measured using the time-kill curve method for two strains.
  
  
  RESULTS
  The MIC(90) values of CSA-13, colistin, tobramycin, and ciprofloxacin were 2, 1, 1, and 2 mg/l, respectively. The MBCs were equal to or two-fold greater than those of the MICs. With a fractional inhibitory concentration index of ≤0.5 as borderline, synergistic interactions were mostly seen with the CSA-13-colistin combination (54%). No antagonism was observed. The results of the time-kill curve analysis demonstrated rapid bactericidal activity of CSA-13 and synergism with colistin; in one strain early synergy was achieved.
  
  
  CONCLUSIONS
  CSA-13 appears to be a good candidate in the treatment of P. aeruginosa strains in CF patients. Future studies should be performed to correlate the safety, efficacy, and pharmacokinetic parameters of this molecule.
authors.affiliation: Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul University, Turkey. caglabozkurt@hotmail.com
authors.forename: Cagla
authors.initials: C
authors.lastname: Bozkurt-Guzel
authors.forename: Paul B
authors.initials: PB
authors.lastname: Savage
authors.forename: Ayse Alev
authors.initials: AA
authors.lastname: Gerceker
mesh_terms: D002939:Ciprofloxacin / Q000008:administration & dosage*; D003091:Colistin / Q000008:administration & dosage*; D003550:Cystic Fibrosis / Q000382:microbiology*; D024901:Drug Resistance, Multiple, Bacterial / Q000502:physiology; D004359:Drug Therapy, Combination; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D013256:Steroids / Q000008:administration & dosage*; D014031:Tobramycin / Q000008:administration & dosage*
chemical_list: D013256:Steroids; C521528:ceragenin CSA-13; D002939:Ciprofloxacin; D014031:Tobramycin; D003091:Colistin