Antimicrobial Activity of Ceragenins against Vancomycin-Susceptible and -Resistant Enterococcus spp.

Ceragenins (CSAs) are a new class of antimicrobial agents designed to mimic the activities of endogenous antimicrobial peptides. In this study, the antibacterial activities of various ceragenins (CSA-13, CSA-44, CSA-90, CSA-131, CSA-138, CSA-142, and CSA-192), linezolid, and daptomycin were assessed against 50 non-repeated Enterococcus spp. (17 of them vancomycin-resistant Enterococcus-VRE) isolated from various clinical specimens. Among the ceragenins evaluated, the MIC50 and MIC90 values of CSA-44 and CSA-192 were the lowest (2 and 4 µg/mL, respectively), and further studies were continued with these two ceragenins. Potential interactions between CSA-44 or CSA-192 and linezolid were tested and synergistic interactions were seen with the CSA-192-linezolid combination against three Enterococcus spp., one of them VRE. The effects of CSA-44 and CSA-192 on the MIC values of vancomycin were also investigated, and the largest MIC change was seen in the vancomycin-CSA-192 combination. The in vivo effects of CSA-44 and CSA-192 were evaluated in a Caenorhabditis elegans model system. Compared to no treatment, increased survival was observed with C. elegans when treated with ceragenins. In conclusion, CSA-44 and CSA-192 appear to be good candidates (alone or in combination) for the treatment of enterococcal infections, including those from VRE.

In vitro activities of antifungals alone and in combination with tigecycline against Candida albicans biofilms.

BACKGROUND: Candida may form biofilms, which are thought to underlie the most recalcitrant infections. METHODS: In this study, activities of antifungal agents alone and in combination with tigecycline against planktonic cells and mature and developing biofilms of Candida albicans isolates were evaluated. RESULTS: Amphotericin B and echinocandins were found to be the most effective agents against mature biofilms, whereas the least effective agent was fluconazole. Furthermore, the most effective anti-fungal monotherapies against biofilm formation were amphotericin B and anidulafungin, and the least effective monotherapy was itraconazole. The combination of tigecycline and amphotericin B yielded synergistic effects, whereas combinations containing itraconazole yielded antagonist effects against planktonic cells. The combination of tigecycline and caspofungin exhibited maximum efficacy against mature biofilms, whereas combinations containing itraconazole exhibited minimal effects. Combinations of tigecycline with amphotericin B or anidulafungin were highly effective against C. albicans biofilm formation. DISCUSSION: In summary, tigecycline was highly active against C. albicans particularly when combined with amphotericin B and echinocandins.