臺灣博碩士論文加值系統

研究背景與目的﹕不適當及過度的抗生素使用與其導致相關的細菌抗藥性病菌的出現是目前一項重大的公共衛生問題。菌血症是一種嚴重的感染症，其導致可觀的罹病率，死亡率和醫療費用支出。而細菌抗藥性的問題進一步減少治療感染症藥物的選擇性並降低病人的安全。本研究為回溯評估一項結合感染症醫師及微生物報告的早期介入菌血症病人處理的抗菌藥物管理方案的介入措施前期、後期的差異。

研究樣本與方法﹕南部一家1,400張病床的醫療中心及2011年377名選定重要致病/抗藥性菌菌血症病人。回溯收集醫院住院病人行政管理資料、藥局藥物使用量及費用、及選定重要致病/抗藥性菌菌血症病人病歷資料。

結果﹕在實施結合感染病專家及微生物實驗室血液培養陽性報告介入前期（2011年1至6月）及介入後期（2011年7月至12月），該醫院內住院病人重要醫療指標並無差異。在介入後期，靜脈注射及口服抗菌藥物的總使用量減少217.8 DDD/1,000 住院病人日(PD) (11.7%)，其中以penicillins、cephalosporins、及quinolones減幅都 >10%﹔全院抗菌藥費、住院抗菌藥費、及平均每住院人日抗菌藥費分別減少7,070,288元(9.0%)、5,991,896元(12.2%)、及40.5元/PD (14.0%)。重要院內感染抗藥性細菌carbapenem-resistant (CR) Acinetobacter baumannii及CR-Pseudomonas aeruginosa抗藥性比率在各屬菌種內呈現下降，分別為50% vs. 43% (p < 0.05)及8.9% vs. 6.0% (p < 0.05)。Etended-spectrum β-lactamase Escherichia coli及vancomycin-resistant Enterococcus faecium抗藥性比率則上升，分別為16.6% vs. 19.2% (p < 0.05)及14.0% vs. 30.7% (p < 0.05)。分析377位重要致病菌菌血症病人，介入前期病人較年長 (72.3 ± 15. vs. 68.8 ± 16.2, p = 0.031)，慢性心臟衰竭較多(10.6% vs. 4.1%, p = 0.018)，長期卧床較多(25.1% vs. 13.5%, p = 0.005)；然而，菌血症嚴重度中，McCabe-Jackon分類則以介入後期終將致命及致命分類較多(p = 0.003) ， 表現急性血液衰竭及肝衰竭的比率亦以後期為高。介入前、後期377位菌血症病人醫療成效的比較：適當抗菌藥物使用延遲時間、適當抗菌藥物被使用時機、及死亡率無差異。

結論﹕本研究強調抗菌藥物管理方案的重要，藉由結合感染症專家及微生物報告的早期主動介入菌血症病人的抗菌藥物管理措施，可有效降低醫院內抗菌藥物的使用量及費用。

Background & Purposes. Inappropriate and over use of antimicrobial agents and its’ related emergence of antimicrobial resistance are major public issues concerned currently. Bacteremia is a severe infection and leads into considerable morbidity, mortality, and medical costs. The emergence of antimicrobial resistance embarrasses the selection in treatment of infectious diseases and injures patient safety. The study was targeted to retrospectively review the impact of an antimicrobial stewardship program by linking early intervention of infectious disease specialists and microbiologic reports on management of bacteremic patients.

Materials & Methods. A 1,400-bed medical center in southern Taiwan and 377 targeted bacteremic patients with important or drug-resistant pathogens. To collect administrative data of hospitalized patients, pharmacy prescription and expenditure, and clinical relevant information, by chart review, in targeted bacteremic patients caused by important or multidrug-resistant pathogens respectively.

Results. Between the pre- and post-intervention phases (January 1, 2011 – June 30,2011 vs. July 1, 2011 – December 31, 2011), there was no difference in administrative indicators. In the post-phase, the amounts in usage of intravenous and oral antimicrobial agents decreased by 217.8 DDD/1,000 inpatients-day (PD) (11.7%); the reduction occurred most in penicillins, cephalosporins, and quinolones (>10%). The expenditure of all antimicrobials, antimicrobials for inpatients, and average daily cost of inpatient-day decreased in post-phase: NT$ 7,070,288(9.0%), NT$5,991,896 (12.2%), and NT$ 40.5/PD (14.0%), respectively. The carbapenem-resistant rate in Acinetobacter baumannii and Pseudomonas aeruginosa decreased from 50% to 43% and 8.9% to 6.0%, respectively (p < 0.05). The percentage of extended-spectrum β-lactamase producing Escherichia coli and vancomycin-resistant Enterococcus faecium increased from 16.6% to 19.2% and from 14.0% to 30.7%, respectively, (p < 0.05). In an analysis of 377 bacteremic patients caused by important pathogens, patients in pre-phase were with older age (72.3 ± 15. vs. 68.8 ± 16.2, p = 0.031), more cases with chronic heart failure (10.6% vs. 4.1%, p = 0.018) and in bed-ridden (25.1% vs. 13.5%, p = 0.005).However, cases in post-phase with higher severity of infection by McCabe-Jackson category (p = 0003), and more cases presenting acute hematologic failure and acute liver failure. In comparison between two phases, there was no difference in delay time between bacteremia onset and use of appropriate antimicrobials, timing of appropriate antimicrobials used, and mortality rate.

Conclusion. This study underlines the importance of antimicrobial stewardship program. By linking early intervention of infectious disease specialists and microbiologic reports on management of bacteremic patients can effectively reduce the expenditure of antimicrobial expenditure in hospital.

目錄
誌謝 i
中文摘要 ii
英文摘要 iv
第一章 緒論 1
第一節、 研究背景 1
第二節、 研究動機 2
第三節、 研究目的 3
第四節、 預期貢獻 4
第五節、 名詞解釋 5
第二章 文獻探討 10
第一節、 菌血症(Bacteremia)的臨床重要性及處理原則 10
第二節、 細菌抗藥性對感染症治療的影響 13
第三節、 抗菌藥物管理方案源由 17
第四節、 抗菌藥物管理方案介紹、施行策略及成效 19
第三章 研究方法 25
第一節、 研究架構和研究假設 25
第二節、 研究設計 29
第三節、 研究材料 30
第四節、 研究變項 32
第五節、 統計分析計畫 34
第四章 研究結果 35
第一節、 介入前、後期住院病人重要指標變化 35
第二節、 介入前、後期抗菌藥物的使用量及費用 36
第三節、 介入前、後期院內重要抗藥性細菌的變化 37
第四節、 介入前、後期Clostridium difficile感染情形 39
第五節、 介入前、後期377位菌血症病人的特性、感染來源及菌種、及發生感染部位等重要指標 40
第六節、 介入前、後期377位菌血症病人的醫療成效差異 41
第七節、 377位菌血症病人的死亡因子分析 42
第五章 討論與結論 43
第一節、 研究目的和研究假設討論 43
第二節、 研究限制 50
第三節、 未來研究方向 51
第四節、 結論和建議 52
第六章 參考文献 53
第七章 附錄……………………………………………………………………………81

表目錄
表一、 在實施結合感染病專家及微生物實驗室血液培養陽性報告早期介入菌血症病人的處理介入前期（2011年1至6月）及介入後期（2011年7至12月）醫院內住院病人重要指標的的變化。…………………………………………62
表二、 在實施結合感染病專家及微生物實驗室血液培養陽性報告早期介入菌血症病人的處理介入前期（2011年1至6月）及介入後期（2011年7至12月）的靜脈注射及口服抗菌藥物使用量， 定義之日劑量（DDD）/1,000住院病人日 (PD)。…………………………………………………………………………63
表三、 在實施結合感染病專家及微生物實驗室血液培養陽性報告早期介入菌血症病人的處理前6個月期間（2011年1至6月）及干預後6個月期間（2011年7月至12月）的靜脈注射抗菌藥物使用量，定義之日劑量（DDD）/1,000住院病人日 (PD)。………………………………………………………………64
表四、 在實施結合感染病專家及微生物實驗室血液培養陽性報告早期介入菌血症病人的處理介入前期（2011年1至6月）及介入後期（2011年7至12月）住院及門診的總藥費及抗菌藥費支出及佔率(%)。……………………………65
表五、 在實施結合感染病專家及微生物實驗室血液培養陽性報告早期介入菌血症病人的處理介入前期（2011年1至6月）及介入後期（2011年7至12月）醫院內重要抗藥性細菌抗藥菌株數及比率的變化。………………………………………………………………………………66
表六、 在實施結合感染病專家及微生物實驗室血液培養陽性報告早期介入菌血症病人的處理前6個月期間（2011年1至6月）及干預後6個月期間（2011年7月至12月）腹瀉病人的糞便C. difficile分離率 (%)變化。……………67
表七、 在實施結合感染病專家及微生物實驗室血液培養陽性報告早期介入菌血症病人的處理介入前期（2011年1至6月）及介入後期（2011年7至12月）醫院內住院病人特性、感染來源及菌種、及發生感染部位等重要指標。………………………………………………………………………………68
表八、 在實施結合感染病專家及微生物實驗室血液培養陽性報告早期介入菌血症病人的處理介入前期（2011年1至6月）及介入後期（2011年7至12月）醫療成效差異比較。……………………………………………………………72
表九、 重要菌血症病人的30日死亡因子分析。………………………………………74
表十、 菌血症病人選擇性死亡危險因子 (N = 377)。………………………………80

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