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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 |
| 顯示於類別: | [保健營養系(所) ] 期刊論文
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