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

YILMAZ F. N., ÖKSÜZ L., Demir E. S., DÖŞLER S., Savage P. B., Guzel C. B.

CURRENT MICROBIOLOGY, cilt.80, sa.10, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 80 Sayı: 10
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1007/s00284-023-03443-5
  • Dergi Adı: CURRENT MICROBIOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, Food Science & Technology Abstracts, Veterinary Science Database
  • İstanbul Üniversitesi Adresli: Evet

Özet

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 mu g/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.