Phenotypic Investigation of Virulence Factors, Susceptibility to Ceragenins, and the Impact of Biofilm Formation on Drug Efficacy in Candida auris Isolates from Türkiye.

Candida auris has emerged as a significant fungal threat due to its rapid worldwide spread since its first appearance, along with its potential for antimicrobial resistance and virulence properties. This study was designed to examine virulence characteristics, the efficacy of ceragenins, and biofilm-derived drug resistance in seven C. auris strains isolated from Turkish intensive care patients. It was observed that none of the tested strains exhibited proteinase or hemolysis activity; however, they demonstrated weak phospholipase and esterase activity. In addition, all strains were identified as having moderate to strong biofilm formation characteristics. Upon determining the minimum inhibitory concentrations (MIC) of ceragenins, it was discovered that CSA-138 exhibited the highest effectiveness with a MIC range of 1-0.5 µg/mL, followed by CSA-131 with a MIC of 1 µg/mL. Also, antimicrobial agents destroyed mature biofilms at high concentrations (40-1280 µg/mL). The investigation revealed that the strains isolated from Türkiye displayed weak exoenzyme activities. Notably, the ceragenins exhibited effectiveness against these strains, suggesting their potential as a viable treatment option.

Efficacy of Ceragenins Alone and in Combinations with Antibiotics Against Multidrug-Resistant Gram Negative Pathogens from Bloodstream Infections.

Ceragenins (CSAs) that mimic the activities of antimicrobial peptides may be new options for the treatment of infections caused by multidrug-resistant pathogens. This study investigated the antibacterial activities of eight different ceragenins against MDR pathogens and the synergistic effects of some ceragenins in combinations with antibiotics (meropenem-MEM, ceftazidime + avibactam-CZA, tigecycline-TIG). A disc diffusion method was used for antibiotic susceptibility tests, a broth microdilution, and checkerboard methods were used to detect minimum inhibitory concentrations (MICs) and the effects of combinations, respectively. While MIC90 values CSA-13, CSA-44, CSA-131 against Klebsiella pneumoniae isolates had similar effect with MEM (8 µg/ml); CSA-13, CSA-44, CSA-131, CSA-138, and CSA-144 had better activity than MEM against Acinetobacter baumannii and Pseudomonas aeruginosa isolates. In particular, CSA-44 and CSA-131 were effective against A. baumannii and P. aeruginosa isolates which resistant to both COL and MEM. CSA-44+MEM and CSA-131+CZA combinations showed synergistic activity against most (70%) of MDR- E. coli isolates. Although TIG is known to have weak activity in nonfermentative bacteria, CSA-44+TIG combination showed synergistic activity against two (17%) of the A. baumanni isolates. In addition, CSA-44+TIG and CSA-131+TIG combinations showed additive effects against all P. aeruginosa isolates. Antagonism was not detected in any of the combinations. CSA-44 and CSA-131 alone/or in combinations with MEM or CZA can be considered as new alternative treatments in serious infections caused by MDR pathogens.

Antibacterial and Antibiofilm Activities of Ceragenins Alone and in Combination with Levofloxacin Against Multidrug Resistant Myroides spp. Clinical Isolates from Patients with Urinary Tract Infections.

Myroides spp. are rare opportunistic pathogens, but they can be life-threatening because of their multidrug-resistant drug properties and their potential to cause outbreaks, especially in immunosuppressed patients. In this study, 33 isolates isolated from intensive care patients with urinary tract infections were examined for drug susceptibility. All isolates except three proved to be resistant to the tested conventional antibiotics. The effects of ceragenins, a class of compounds developed to mimic endogenous antimicrobial peptides, were evaluated against these organisms. The MIC values of nine ceragenins were determined, and the most effective ceragenins were CSA-131 and CSA-138. Three isolates that were susceptible to levofloxacin and two isolates resistant to all antibiotics underwent 16 s rDNA analysis, and whereas resistant isolates were identified as M. odoratus, susceptible isolates were identified as M. odoratimimus. CSA-131 and CSA-138 showed rapid antimicrobial effects observed in time-kill analyses. Combinations of ceragenins and levofloxacin caused a significant increase in antimicrobial and antibiofilm activities against M. odoratimimus isolates. In this study, Myroides spp. were found to be multidrug-resistant and have biofilm forming capacity, and ceragenins CSA-131 and CSA-138 were found to be especially effective on both planktonic and biofilm forms of Myroides spp.

In vitro activity of ceragenins against Burkholderia cepacia complex.

Burkholderia cepacia complex (Bcc) species are aerobic, Gram-negative and non-fermantative bacilli. Bcc can cause clinical symptoms in patients with cystic fibrosis, ranging from asymptomatic carriage to fatal pneumonia. A pressing need exists for new antimicrobial agents that target Bcc. Ceragenins, CSA-13, CSA-131 and CSA-131 with 5% Pluronic® F127 (CSA-131P), were evaluated against Bcc clinical isolates (n = 42). MICs of ceragenins and conventional antibiotics were determined. Time-kill curve experiments were performed with 1x, 4x MICs of ceragenins and sulfamethoxazole-trimethoprim (SXT), levofloxacin. MIC50/ MIC90 results (mg l-1) of CSA-13, CSA-131 and CSA-131P were determined as 16/64, 16/128 and 16/128, respectively. CSA-13 and CSA-131 showed bactericidal activity. CSA-13 - levofloxacin combination displayed synergistic activity against Bcc. First-generation (CSA-13) and second-generation (CSA-131 and CSA-131P) ceragenins have significant antimicrobial effects on Bcc. The findings of this study demonstrate that combinations of ceragenins with currently marketed antibiotics could be synergistic in vitro against Bcc isolates. These results suggest that combination therapy with conventional antibiotics could be an alternative approach for treating Bcc infections in the future.