title: Potential synergy activity of the novel ceragenin, CSA-13, against clinical isolates of Pseudomonas aeruginosa, including multidrug-resistant P. aeruginosa.
abstract: OBJECTIVE
  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.
authors: Anti-infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA.
authors: Judy N
authors: JN
authors: Chin
authors: Ronald N
authors: RN
authors: Jones
authors: Helio S
authors: HS
authors: Sader
authors: Paul B
authors: PB
authors: Savage
authors: Michael J
authors: MJ
authors: Rybak
mesh_terms: D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects* / Q000502:physiology; D004357:Drug Synergism; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification*; D013256:Steroids / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D013256:Steroids; C521528:ceragenin CSA-13