Potential synergy activity of the novel ceragenin, CSA-13, against clinical isolates of Pseudomonas aeruginosa, including multidrug-resistant P. aeruginosa

Abstract

Objectives: Previous data from our research had shown that the novel ceragenin, CSA-13, demonstrated concentration-dependent bactericidal activity against glycopeptide-resistant Staphylococcus aureus. However, it is unknown whether CSA-13 demonstrates a similar property against Pseudomonas aeruginosa. We evaluated CSA-13 antipseudomonal activity compared with cefepime, meropenem, piperacillin/tazobactam, tobramycin and ciprofloxacin by susceptibility testing as well as in combination with cefepime, tobramycin and ciprofloxacin.

Methods: Fifty clinical isolates of P. aeruginosa were analysed by reference broth microdilution methods. Four strains with various susceptibilities were evaluated by time-killing curve (TKC) analysis at 0.5x, 1x, 2x and 4x MIC using an initial inoculum of 10(6) cfu/mL. For synergy testing, TKC analysis of CSA-13 alone and in combination with cefepime, tobramycin and ciprofloxacin at 0.5x MIC was performed.

Results: CSA-13 MIC50 and MBC50 were 16 and 16 mg/L, respectively. TKC analysis demonstrated concentration-dependent activity, with CSA-13 at 4x MIC achieving earliest kill at 1 h (99.9%, detection limit). Combination TKC analysis demonstrated synergy or additive effect with cefepime and ciprofloxacin, in some cases achieving early synergy. The addition of tobramycin to CSA-13 resulted in no difference in kill for two strains.

Conclusions: CSA-13 showed concentration-dependent activity against clinical isolates of P. aeruginosa, including multidrug-resistant P. aeruginosa. The addition of cefepime or ciprofloxacin to CSA-13 enhanced bacterial kill, achieving early synergy.