Carbapenem 類抗生素是目前用於治療產生 AmpC- 和超廣效性 β-lactamases 的腸內菌所感染之病患。因此，carbapenem 類抗生素便成為治療腸內菌之重要的抗生素。Enterobacter cloacae 是非常重要的醫院院內感染之病原菌，由於其天生會產生 AmpC-β-lactamases 之特性，造成 E. cloacae 菌株通常對於廣效性頭孢素類的抗生素具有高度抗藥性存在。本研究目標是探討在成功大學附設醫院的 ertapenem 非敏感性 E. cloacae 臨床菌株之抗藥性分析。本實驗收集 2007 年 355 株不重複之臨床菌株，其中 53 (14.9%) 株對於 ertapenem 具有抗藥性。這 53 株 ertapenem 非敏感性菌株中有 40 (75.5%) 株會表現 SHV-type 超廣效性 β-lactamases，此外 46 株 (86.8%) 會表現 TEM-type β-lactamases。利用脈衝式電泳進行 53 株臨床菌株之分析發現，共可分為 23 種圖譜，其中 35 株可分為 5 種主要的圖譜。萃取 E. cloacae 臨床菌株之外套膜蛋白質分析發現，42 (79.2%) 株 ertapenem 非敏感性 E. cloacae 菌株之外套膜蛋白質表現量並沒有明顯差異。互補菌株之 OmpC 或 OmpF 的表現不會影響其對 ertapenem 的敏感性。加入 efflux pump 抑制劑 carbonyl cyanide m-chlorophenylhydrazone (CCCP) 後，E. cloacae 臨床菌株之 ertapenem 最小抑制濃度下降約 8 到 16 倍 (從 16 μg/ml 下降至 2 μg/ml)，然而加入 phenylalanine argine β-naphthylamide (PAβN) 抑制劑後其 MICs 僅有 4 倍之差異。從本實驗中發現，我們收集的菌株中以超廣效性 β-lactamases 酵素的產生與 efflux pump 的活性兩種抗藥機轉同時發生時是造成 E. cloacae 臨床菌株對 ertapenem 敏感性降低的主要原因。

Carbapenems are most frequent agents used for treating infections caused by AmpC- and extended-spectrum-β-lactamases (ESBLs)-producing Enterobacteriaceae. Therefore, the emergence of carbapenem resistance in Enterobacteriaceae has become a great concern. Enterobacter cloacae, an important nosocomial pathogen, may become resistant to broadspectrum cephalosporins by constitutive expression of its chromosomal AmpC β-lactamase. The aim of this study was to characterize ertapenem-non-susceptible (ETP-NS) E. cloacae isolates in National Cheng Kung University Hospital. The present study demonstrated that 53 of 355 (14.9 %) E. cloacae isolates were ETP-NS in 2007. Among them, 40 (75.5 %) of the ETP-NS E. cloacae isolates had ESBLs, and all were found to produce the SHV-type ESBLs. In addition, 46 (86.8%) isolates had the TEM-type β- lactamases. Twenty-three patterns were pulsed-field gel electrophoresis (PFGE) analysis. Five major patterns dominated for 35 ETP-NS isolates. No discernible change in the expression of outer membrane proteins was found in most (n=42, 79.2%) of strains. Overexpression of OmpC or OmpF in complemented strain had no effect on ertapenem susceptibility. The MICs of ertapenem in the presence of pump inhibitor, carbonyl-cyanide- m-chlorophenylhydrazone (CCCP), had 8 to 16-fold decreased (from 16 to 2 μg/ml). However, the presence of phenylalanine- argine-β-naphthylamide (PAβN) had no significant effect on the result of MIC for most isolates, which reduced less than 4 fold. This study suggests that the decreased susceptibility to ertapenem in E. cloacae in the hospital may arise largely by the production of ESBLs combined with the efflux pump expression in this region.

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