2013-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/646226摘要：鮑氏不動桿菌(Acinetobacter baumannii)近年來在全世界成為重要的院內致病菌之一。目前歐洲､北美､亞洲､中東､澳洲等地都有發生規模不小的不動桿菌群突發。常見不動桿菌感染的臨床表現為肺炎、菌血症、軟組織感染及腦膜炎等。菌血症死亡率在非加護病房病患為16.3%､而在加護病房病患死亡率可高達34.0-43.4%。面對抗生素的壓力，此細菌對各式抗生素快速發展出多重抗藥性，故一旦感染，相當難以治療。根據臺大醫院的資料，對傳統5 或6 種抗生素有抗藥性的不動桿菌菌血症佔所有不動桿菌菌血症的比例，在西元2007, 2008, 2009 年，分別為24.9% (54/217), 33.7% (68/202), 32.2%(86/267)。Colistin 雖然是一種在1950 年代就被發現的抗生素，但因為發現它目前對革蘭氏陰性菌有相當好的抗菌效果，因此被考慮用於對其它抗生素都抗藥的細菌所引起的感染做為拯救治療。但是過去很少有前瞻性的觀察研究colistin 用於治療不動桿菌菌血症的療效，且因預測病人預後及治療效果常受到許多的干擾因素影響，因此對於療效的評估不易且缺乏有效的預測性生物標記。“代謝體分析”(Metabolomics)可分析在不同狀況下體液中各種小分子量的代謝物特徵(Metabolic fingerprinting)。目前已有少數研究顯示代謝體分析可以用來尋找有效的敗血症預測性生物標記。另外過去研究也證實即時聚合酶鏈鎖反應能偵測病人血中菌量且不受病人的其它干擾因素影響，能直接反應病人的預後。因此我們將前瞻性的觀察不動桿菌菌血症使用colistin 治療的狀況，利用代謝體分析，及聚合酶鏈鎖反應偵測病患血中菌量，分析影響病患預後的因子，找出最適的colstin 使用方式(合併合種藥物，或單一治療)，並找到敏感的預測性生物標記。<br> Abstract: Acinetobacter baumannii (A. baumannii) have emerged as an important pathogen inhospital settings worldwide. Numerous outbreaks of A. baumannii have been documented inEurope, North America, Asia, Middle East, and Australia. Moreover, the clinical problem withAcinetobacter species is not only of magnitude but also of severity. Mortality of bacteremiacaused by Acinetobacter species is significantly higher than that by other Gram-negativebacteria (57% vs. 31-43%, p<0.05). Acinetobacter species employ several resistancemechanisms enabling survival under selective antimicrobial pressure, and specific treatmentis further complicated by multidrug resistance. At our hospital, the percentage of bacteremiacaused by highly resistant Acinetobacter species, defined as isolates resistant to 5 or 6antimicrobial classes in all bacteremia caused by Acinetobacter species is 24.9% (54/217),33.7% (68/202) and 32.2% (86/267) in 2007, 2008 and 2009, respectively.Colistin (also known as polymyxin E) is a multi-component polypeptide antibioticdiscovered in the 1950s. Owing to its significant (currently high) activity againstGram-negative ‘superbugs’, including A. baumannii, colistin is now being administered as‘salvage’ therapy in patients in whom none of the other available antibiotics are active againsttheir isolate. However, there was no prospective study which focused on the treatmentefficacy of colistin in treating A. baumannii bacteremia. Multiple confounding factors maketreatment response difficult to evaluate. There is also no sensitive biomarker to predict clinicaloutcome.“Metabolomics” is defined as the quantitative measurement of the dynamic metabolicresponse (small molecular weight metabolites) of living systems to patho-physiologicalstimuli or genetic modification. There were also studies showed metabolomics approach canbe used to find sensitive biomarker to predict the progress of sepsis. Real-time PCR had beenused to quantify bacterial load of bacteremia and can reflect clinical outcome independently.Thus, we will conduct a prospective study, which observe the clinical response of colistinin treating A. baumannii bacteremia. Using metabolomics approach, and real-time PCR toquantify the bacterial load, we aim to find outcome predictors, the best colistin treatment(combination regimens, or monotherapy) and also to find new sensitive biomarkers.鮑氏不動桿菌菌血症colistinAbaumanniibacteremiacolistin