使用头孢吡肟、头孢他啶或头孢托罗匹酯对铜绿假单胞菌一步 AmpC 或外排突变体进行差异选择。
Differential selection of single-step AmpC or efflux mutants of Pseudomonas aeruginosa by using cefepime, ceftazidime, or ceftobiprole.
机构信息
Johnson & Johnson Pharmaceutical Research and Development, LLC, 1000 Route 202 South, Raritan, NJ 08869, USA.
出版信息
Antimicrob Agents Chemother. 2010 Oct;54(10):4092-7. doi: 10.1128/AAC.00060-10. Epub 2010 Jul 6.
Abstract
Single-step Pseudomonas aeruginosa mutants, selected with ceftobiprole, ceftazidime, or cefepime, were generated at frequencies of 10(-6) to <10(-9) at two and four times the MIC. The chromosomal AmpC β-lactamase activity was increased in all ceftazidime-selected mutants. Mutants selected with cefepime either increased AmpC activity or upregulated expression of the mexXY efflux genes. Mutants selected with ceftobiprole did not overexpress AmpC; 90% of these produced elevated levels of mexXY RNA, indicating that increased efflux, not AmpC derepression, is the predominant response to ceftobiprole during first-step mutations in P. aeruginosa.
摘要
在两倍和四倍 MIC 时，用头孢他啶、头孢噻肟或头孢吡肟选择可产生频率为 10(-6) 到 <10(-9) 的一步突变单菌 Pseudomonas aeruginosa。在所有头孢他啶选择的突变体中，染色体 AmpC β-内酰胺酶活性增加。用头孢吡肟选择的突变体增加 AmpC 活性或上调 mexXY 外排基因的表达。用头孢比普酯选择的突变体不高表达 AmpC；90%的突变体产生高水平的 mexXY RNA，表明在铜绿假单胞菌第一步突变中，增加外排而不是 AmpC 去阻遏是对头孢比普酯的主要反应。
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