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

被引:89
作者
Chin, Judy N. [1 ]
Jones, Ronald N. [3 ]
Sader, Helio S. [3 ]
Savage, Paul B. [2 ]
Rybak, Michael J. [1 ]
机构
[1] Wayne State Univ, Eugene Applebaum Coll Pharm & Hlth Sci, Dept Pharm Practice, Antiinfect Res Lab, Detroit, MI 48201 USA
[2] Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA
[3] JMI Labs, N Liberty, IA USA
关键词
Gram-negative; cationic steroid antimicrobial; resistance;
D O I
10.1093/jac/dkm457
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
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.
引用
收藏
页码:365 / 370
页数:6
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