Objectives: The ceragenins, or CSAs, were designed to mimic the activities of antimicrobial\npeptides and represent a new class of antimicrobial agent. The aim of this study was to comparatively\ninvestigate the antimicrobial activities of first/second generation ceragenins and various antibiotics\nagainst multidrug-resistant (MDR) Klebsiella pneumoniae, including colistin-resistant bacteria. Also,\nthe synergistic effects of two ceragenins with colistin or meropenem were investigated with\nsix K. pneumoniae strains presenting different resistant patterns. Methods: Minimal inhibition\nconcentrations (MICs) were determined by the microdilution method according to the CLSI. Antibiotic\ncombination studies were evaluated by the time-kill curve method. Results: MIC50 and MIC90 values\nof tested ceragenins ranged from 8 to 32 mg/L and 16 to 128 mg/L. Overall, among the ceragenins\ntested, CSA-131 showed the lowest MIC50 and MIC90 values against all microorganisms. The MICs of\nthe ceragenins were similar or better than tested antibiotics, except for colistin. Synergistic activities\nof CSA-131 in combination with colistin was found for strains both at 1* MIC and 4* MIC. No\nantagonism was observed with any combination. Conclusions: First-generation ceragenins CSA-13\nand CSA-44 and second-generation ceragenins CSA-131, CSA-138 and CSA-142 have significant\nantimicrobial effects on MDR K. pneumoniae. Mechanisms allowing resistance to clinical comparator\nantibiotics like colistin did not impact the activity of ceragenins. These results suggest that ceragenins\nmay play a role in treating infections that are resistant to known antibiotics.
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