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. CONCLUSION: 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.
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. CONCLUSION:CSA-13 appears to be a good candidate in the treatment of P. aeruginosa strains in CFpatients. Future studies should be performed to correlate the safety, efficacy, and pharmacokinetic parameters of this molecule.
Authors: Katarzyna Niemirowicz; Ewelina Piktel; Agnieszka Z Wilczewska; Karolina H Markiewicz; Bonita Durnaś; Marzena Wątek; Irena Puszkarz; Marta Wróblewska; Wiesława Niklińska; Paul B Savage; Robert Bucki Journal: Int J Nanomedicine Date: 2016-10-19
Authors: Ewelina Piktel; Katarzyna Pogoda; Maciej Roman; Katarzyna Niemirowicz; Grażyna Tokajuk; Marta Wróblewska; Beata Szynaka; Wojciech M Kwiatek; Paul B Savage; Robert Bucki Journal: Sci Rep Date: 2017-03-15 Impact factor: 4.379