JAC Advance Access originally published online on December 12, 2007
Journal of Antimicrobial Chemotherapy 2008 61(2):365-370; doi:10.1093/jac/dkm457
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Original research |
Potential synergy activity of the novel ceragenin, CSA-13, against clinical isolates of Pseudomonas aeruginosa, including multidrug-resistant P. aeruginosa
1 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 2 JMI Laboratories, North Liberty, IA, USA 3 Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA
Received 15 August 2007; returned 23 September 2007; revised 23 October 2007; accepted 30 October 2007
* Corresponding author. Tel: +1-313-577-4376; Fax: +1-313-577-8915; E-mail: m.rybak{at}wayne.edu
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 106 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.
Keywords: Gram-negative , cationic steroid antimicrobial , resistance
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. N. Leonard, G. W. Kaatz, L. R. Rucker, and M. J. Rybak Synergy between gemifloxacin and trimethoprim/sulfamethoxazole against community-associated methicillin-resistant Staphylococcus aureus J. Antimicrob. Chemother., December 1, 2008; 62(6): 1305 - 1310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bucki, D. B. Namiot, Z. Namiot, P. B. Savage, and P. A. Janmey Salivary mucins inhibit antibacterial activity of the cathelicidin-derived LL-37 peptide but not the cationic steroid CSA-13 J. Antimicrob. Chemother., August 1, 2008; 62(2): 329 - 335. [Abstract] [Full Text] [PDF]
|
|