Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul University, Istanbul, Türkiye.
Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University, 34093-Capa-Fatih, Istanbul, Türkiye.
Curr Microbiol. 2023 Aug 24;80(10):327. 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 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.
模拟抗菌肽活性的鲨烯胺（CSAs）可能成为治疗多重耐药病原体引起感染的新选择。本研究调查了 8 种不同的鲨烯胺对多重耐药病原体的抗菌活性，以及一些鲨烯胺与抗生素（美罗培南-MEM、头孢他啶+阿维巴坦-CZA、替加环素-TIG）联合使用的协同作用。采用纸片扩散法进行抗生素药敏试验，肉汤微量稀释法和棋盘法分别用于检测最小抑菌浓度（MIC）和组合的协同作用。CSA-13、CSA-44 和 CSA-131 对肺炎克雷伯菌的 MIC 值与 MEM（8μg/ml）相似；CSA-13、CSA-44、CSA-131、CSA-138 和 CSA-144 对鲍曼不动杆菌和铜绿假单胞菌的活性均优于 MEM。特别是 CSA-44 和 CSA-131 对同时对 COL 和 MEM 耐药的鲍曼不动杆菌和铜绿假单胞菌具有活性。CSA-44+MEM 和 CSA-131+CZA 联合用药对大多数（70%）多重耐药性大肠杆菌的活性表现出协同作用。虽然 TIG 已知对非发酵菌活性较弱，但 CSA-44+TIG 联合用药对 2 株（17%）鲍曼不动杆菌具有协同作用。此外，CSA-44+TIG 和 CSA-131+TIG 联合用药对所有铜绿假单胞菌均表现出相加作用。在任何组合中均未检测到拮抗作用。CSA-44 和 CSA-131 单独或与 MEM 或 CZA 联合使用可作为治疗由多重耐药病原体引起的严重感染的新选择。
