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    Ceragenins exhibiting promising antimicrobial activity against various multidrug resistant Gram negative bacteria
    (Istanbul Univ, Fac Pharmacy, 2018) Oyardi, Ozlem; Savage, Paul B.; Alper Akçalı; Erturan, Zayre; Bozkurt-Guzel, Cagla
    Ceragenins are novel promising agents for the treatment of infections caused by multi-drug resistant microorganisms. Since colistin resistance has become a worldwide problem, the need for new treatment agents has been increasing steadily. Therefore, this study aimed to investigate in vitro antimicrobial activities of ceragenins (Cationic Steroid Antibiotics) (CSA-8, CSA-13, CSA-142 and CSA-192) against multidrug resistant Gram negative isolates from Turkey. Experiments were performed by using broth microdilution method against Klebsiella pneumoniae, Morganella morganii, Pseudomonas aeruginosa and Stenotrophomonas maltophilia isolates. All microorganisms except for three isolates were identified as multidrug resistant. Among tested ceragenins, CSA-13 showed the best results (MIC: 8-64 mu g/ml). Nevertheless, the antimicrobial activity of CSA-8 was not significant. In conclusion, ceragenins appear to be a good candidate as antimicrobial therapy in the presence of multidrug (including colistin) resistant microorganisms.
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    Potential Synergy Activity of the Novel Ceragenin, CSA-13, against Carbapenem-Resistant Acinetobacter baumannii Strains Isolated from Bacteremia Patients
    (Hindawi Ltd, 2014) Bozkurt-Guzel, Cagla; Savage, Paul B.; Alper Akçalı; Ozbek-Celik, Berna
    Carbapenem-resistant Acinetobacter baumannii is an important cause of nosocomial infections, particularly in patients in the intensive care units. As chronic infections are difficult to treat, attempts have been made to discover new antimicrobials. Ceragenins, designed to mimic the activities of antimicrobial peptides, are a new class of antimicrobial agents. In this study, the in vitro activities of CSA-13 either alone or in combination with colistin (sulphate), tobramycin, and ciprofloxacin were investigated using 60 carbapenem-resistant A. baumannii strains isolated from bacteremia patients blood specimens. MICs and MBCs were determined by microbroth dilution technique. Combinations were assessed by using checkerboard technique. The MIC50 values (mg/L) of CSA-13, colistin, tobramycin, and ciprofloxacin were 2, 1, 1.25, and 80, respectively. The MIC90 (mg/L) of CSA-13 and colistin were 8 and 4. The MBCs were equal to or twice greater than those of the MICs. Synergistic interactions were mostly seen with CSA-13-colistin (55%), whereas the least synergistic interactions were observed in the CSA-13-tobramycin (35%) combination. No antagonism was observed. CSA-13 appears to be a good candidate for further investigations in the treatment of A. baumannii infections. However, future studies should be performed to correlate the safety, efficacy, and pharmacokinetic parameters of this molecule.