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

• Published in: Current microbiology 2023-10, Vol.80 (10), p.327-327, Article 327
• Main Authors: Yilmaz, Fatima Nur, Öksüz, Lütfiye, Demir, Elif Sena, Döşler, Sibel, Savage, Paul B., Güzel, Çağla Bozkurt
• Format: Article
• Language: English
• Subjects: Acinetobacter baumannii; Antagonism; Antibacterial activity; antibiotic resistance; Antibiotics; Antimicrobial peptides; Biomedical and Life Sciences; Biotechnology; blood flow; Ceftazidime; Drug resistance; E coli; Escherichia coli; Infections; Klebsiella; Klebsiella pneumoniae; Life Sciences; Meropenem; Microbiology; minimum inhibitory concentration; Multidrug resistance; Multidrug resistant organisms; multiple drug resistance; Pathogens; Peptides; Pseudomonas aeruginosa; synergism; Synergistic effect; Tigecycline
• ISSN: 0343-8651; 1432-0991
• DOI: 10.1007/s00284-023-03443-5

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 MIC 90 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.