Use of carbapenems against clinical, nontyphoid Salmonella isolates: Results from In Vitro and In Vivo animal studies

Hung Jen Tang, Chi Chung Chen, Chun Cheng Zhang, Kuo Chen Cheng, Shyh Ren Chiang, Yu Hsin Chiu, Yee Huang Ku, Wen Chien Ko, Yin Ching Chuang

研究成果: Article同行評審

6 引文 斯高帕斯(Scopus)

摘要

The emergence of multidrug-resistant Salmonella isolates has created the need for new therapeutic agents. We evaluated the intracellular activity of four carbapenem compounds against clinical nontyphoid Salmonella (NTS) isolates in vitro and ex vivo. Subsequently, the efficacy of carbapenem treatment against selected Salmonella isolates in vivo was assessed using a murine peritonitis model. The MIC50 and MIC90 for doripenem, ertapenem, imipenem, and meropenem against 126 NTS isolates were found to be 0.062 and 0.062, 0.015 and 0.015, 0.5 and 1, and 0.031 and 0.031 μg/ml, respectively. The intracellular killing effect of ertapenem was sustained for 24 h and was superior to that of imipenem, meropenem, and doripenem; its effect was comparable to that of ceftriaxone. Ertapenem demonstrated an excellent pharmacokinetic profile with a percent time above the MIC of 75.5% and an area under the concentration-time curve/MIC ratio of 20,733. When peritoneal exudate cells were examined directly ex vivo from mice with Salmonella-induced peritonitis, cells from mice treated with ertapenem and ceftriaxone had intracellular and extracellular bacterial counts reduced 102- to 104-fold and exhibited killing effects similar to each other. The survival rates of mice inoculated with 1 × 105 and 10 6 CFU of a ceftriaxone-susceptible Salmonella isolate that were subsequently treated with ertapenem or ceftriaxone were 100% and 90%, respectively. When mice were inoculated with 5 × 104 and 105 CFU of a ceftriaxone-resistant and ciprofloxacin-resistant Salmonella isolate, mice treated with ertapenem had a higher survival rate than mice treated with ceftriaxone (70% versus 0% and 50% versus 0%, respectively; P < 0.001). Our results suggest that ertapenem is at least as effective as ceftriaxone in treating murine Salmonella infections and show that further clinical investigations on the potential use of ertapenem in treatment of human Salmonella infections are warranted.

原文English
頁(從 - 到)2916-2922
頁數7
期刊Antimicrobial agents and chemotherapy
56
發行號6
DOIs
出版狀態Published - 2012 六月

All Science Journal Classification (ASJC) codes

  • 藥理
  • 藥學(醫學)
  • 傳染性疾病

指紋

深入研究「Use of carbapenems against clinical, nontyphoid Salmonella isolates: Results from In Vitro and In Vivo animal studies」主題。共同形成了獨特的指紋。

引用此