Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/27639
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    標題: Use of Carbapenems against Clinical, Nontyphoid Salmonella Isolates: Results from In Vitro and In Vivo Animal Studies
    作者: Tang, Hung-Jen
    Chen, Chi-Chung
    Zhang, Chun-Cheng
    Cheng, Kuo Chen
    Chiang, Shyh-Ren
    Chiu, Yu-Hsin
    Ku, Yee Huang
    Ko, Wen-Chien
    Chuang, Yin-Ching
    貢獻者: 保健營養系
    關鍵字: Increasing Ceftriaxone Resistance
    Enterica Serotype Choleraesuis
    Healthy-Volunteers
    Streptococcus-Pneumoniae
    Pharmacokinetics
    Ciprofloxacin
    Tigecycline
    Taiwan
    Meropenem
    Imipenem
    日期: 2012-06
    上傳時間: 2014-03-21 16:16:07 (UTC+8)
    出版者: Amer Soc Microbiology
    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 mu g/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 10(2)- to 10(4)-fold and exhibited killing effects similar to each other. The survival rates of mice inoculated with 1 X 10(5) 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 x 10(4) and 10(5) 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.
    關聯: Antimicrobial Agents And Chemotherapy, 56(6), 2916-2922
    显示于类别:[保健營養系(所) ] 期刊論文

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