背景
產生廣效性乙內醯胺酶(extended-spectrum beta-lactamase, ESBL)的菌種越來越普遍出現在院內與社區之感染症，檢測ESBL表現型的標準方法已被建立，carbapenem或ciprofloxacin被建議治療ESBL細菌的感染症。然而，對廣效頭孢菌素(extended-spectrum cephalosporin, ESC)有抗藥性且非ESBL細菌之感染症尚無一致的理想治療藥物。

研究目的
評估對廣效頭孢菌素具有抗藥性，且非ESBL表現型的Escherichia coli或Klebsiella pneumoniae菌血症，以第四代頭孢菌素或carbapenem藥物治療的效果。

研究方法
研究類型：
以回顧病歷方式進行的回溯性研究。
研究對象：
自民國九十二年七月到九十五年十二月間，收入發生非ESBL表現型的E. coli或K. pneumoniae菌血症的成大醫院病患，其菌血症的細菌敏感性試驗結果，對任一個第三代頭孢菌素具有抗藥性，且對第四代頭孢菌素和carbapenems具有敏感性。只收入病患第一次發生的菌血症，年紀小於16歲病患或病歷記載不完整者予以排除。
評估指標：
主要的評估指標為菌血症後14天的死亡率。

結果
研究期間，總共收入163個對廣效頭孢菌素具有抗藥性，且非ESBL表現型的菌血症病患，菌血症發生後14天的死亡率為18.4%，30天死亡率為24.5%。依治療藥物分成三組，單獨使用第四代頭孢菌素 (46人)、單獨使用carbapenem (24人)、其他組 (24人)。在基本資料方面，如年齡、性別、潛在疾病、感染來源、危險因子或併發症，在此三組皆無有意義的差異。然而，由APACH II score評估的疾病嚴重程度，在carbapenem組傾向高於第四代頭孢菌素組 (P=0.15)。在14天死亡率方面，第四代頭孢菌素組為2.2%，而carbapenem組為16.7% (P=0.045)。然而，若單看APACH II score大於16分者 (P=0.15)或使用多變項回歸校正後 (P=0.14)，兩組14天死亡率並無有意義的差別。

結論
感染對廣效頭孢菌素具有抗藥性，且非ESBL表現型的E. coli或K. pneumoniae菌血症患者，在確定性治療時，使用第四代頭孢菌素治療效果不比carbapenem差。

Background
Extended-spectrum beta-lactamase (ESBL)-producing organisms become more and more prevalent not only in nosocomial, but also in community-acquired infections. Standard methods for ESBL phenotype detection had been established. A carbapenem or ciprofloxacin is recommended for infections caused by ESBL-producing organisms. However, there is no consensus for optimal therapeutic agents for extended-spectrum cephalosporin (ESC) resistant infections without the ESBL phenotype.

Objective
We aimed to evaluate therapeutic outcomes of bacteremia caused by ESC-resistant Escherichia coli or Klebsiella pneumoniae strains without ESBL phenotype treated by a 4th-generation cephalosporin or carbapenem .

Method
Design：
A retrospective review of medical records.
Subjective：
Patients with bacteremia caused by E. coli and K. pneumoniae with a specific resistant phenotype from July 2003 to December 2006 at National Cheng Kung University Hospital were included. The specific resistant phenotype indicated the absence of ESBL phenotype, and resistance to one of 3rd-generation cephalosporins and susceptibility to 4th-generation cephalosporins and carbapenems. Only the fist episode of each patient was included in the analysis. Those younger than 16 years old or with incomplete medical records were excluded.
Endpoint：
Primary endpoint of the present study was the mortality rate at 14 days.

Results
During the study period, 163 patients had bacteremia due to non-ESBL and ESC-resistant organisms. The mortality rate at 14 days after onset was 18.4%, and at 30 days 24.5%. Forty-six patients were treated by 4th-gerenation cephalosporin monotherapy, 24 by carbapenem monotherapy, and 24 by other antibiotics. In baseline data, such as age, gender, underlying diseases, infection sources, risk factors or complications, there was no significant difference among three groups. However, the severity of acute illness, indicated by APACH II score, among patients treated by carbapenem monotherapy tended to be higher than that of those treated by 4th-gerenation cephalosporin monotherapy (P=0.15). The 14-day mortality rate of 4th-gerenation cephalosporin monotherapy was 2.2%, and in contrast that of carbapenem monotherapy was 16.7% (P=0.045). However, the 14-day mortality rates of two groups were not significantly different in patients with severe infections (i.e, APACH II scores ≥16) (P=0.15) or in multiple regression analysis (P=0.14).

Conclusion
For bacteremia caused by ESC-resistant E. coli or K. pneumoniae strains without ESBL phenotype, the therapeutic efficacy of 4th-gerneration cephalosporins as definitive therapy was not inferior to that of carbapenems.

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