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研究生:胡菩芳
研究生(外文):Pu-Fang Hu
論文名稱:探討抗生素封存療法對於透析導管相關感染症的效果
論文名稱(外文):Effects of Antibiotic-lock Therapy on Dialytic Catheter-related Infections
指導教授:高雅慧高雅慧引用關係
指導教授(外文):Yea-Huei Yang Kao
學位類別:碩士
校院名稱:國立成功大學
系所名稱:臨床藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:103
中文關鍵詞:血液透析導管感染抗生素封存溶液抗生素封存療法生物膜生成
外文關鍵詞:dialytic catheter-related infectionantibiotic-lock therapybiofilm formationantibiotic-lock solution
相關次數:
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  • 下載下載:33
  • 收藏至我的研究室書目清單書目收藏:0
使用中央靜脈導管進行透析引起感染症之機率遠高於動靜脈廔管或植體,且造成的菌血症不易由一般靜脈給予抗生素治療成功,主要因為細菌的生物膜生成使細菌不易被抗生素殺除,容易造成管路感染症不斷復發。因此發展出抗生素封存療法(Antibiotic-lock therapy, ALT):在不移除洗腎所需要的透析導管下,於不使用管路的期間,將抗生素留置於導管內,利用局部的高濃度抗生素達到殺除產生生物膜之細菌的目的。目前已知感染菌種的不同將影響治療成敗,但本研究希望能更深入探討影響治療或預防成功與失敗的因子,包括是否與生物膜的生成能力強弱有關。
本研究為一含有前瞻性及回溯性之研究,前瞻性組別收錄2008.12.1 ~2009.5.15期間,於成大醫院發生懷疑有透析導管感染的患者,依治療或預防的需要分別給予抗生素封存療法,治療組共治療3週,預防組則使用2週。並於研究期間作血液培養以確認是否長菌並做菌種及生物膜分析。回溯性組別則收集過去兩年內因懷疑導管相關感染而置換管路的病患之資料,從中挑出與治療組相似的病患做為控制組,而完整的回溯性資料則與預防組的資料做比較。
於研究期間內最後共6名病患納入治療組,並都達到短期治療成功之標準,而長期治療成功率則為66.7 %。另外則有16位病患進入預防組,最後總計預防成功率為62.5 %。病歷回溯組則記錄了100位病患資料,包含了130次懷疑透析導管感染事件。
研究族群中有高達近七成病患多以發燒為主要臨床表徵,且在63.7 %陽性細菌培養結果中,格蘭氏陽性菌佔66.27 %,格蘭氏陰性菌佔23.67 %,另外有10.06 %的病患則培養出黴菌。
長期治療成功與治療失敗之所有評估指標皆未達統計上之顯著差異。又另外由病歷回溯組中挑選出符合與治療組相同納入標準之病患共52位作為病歷對照組。治療成功與病歷對照組病患之生命徵象及生理指標也皆未達到統計學上之顯著差異。但在住院天數部分,治療成功組較病歷對照組短(12.00天vs. 35.12天, p = 0.04 )。治療失敗與病歷對照組病患之生命徵象、生理指標及成效評估指標也皆未達到統計學上之顯著差異。
預防成功與失敗組在各生理數值均無顯著差異。而預防成功之病患收縮壓比病歷回溯組顯著較高(160.00 vs. 138.67 mmHg, p = 0.047),且血紅素及血小板數值也顯著的高於病歷回溯組(p = 0.036 and 0.030),其餘部分則無顯著差異。預防失敗組與病歷回溯組之整體生理特性皆相似,所有數值均無顯著差異。
預防組之成效採用PDIR及CRII做為成效指標,PDIR數值越高表示越容易發生感染事件,而CRII值高則表示當次感染需使用較久之抗生素,可能意味著感染較嚴重。經計算後,預防成功組之PDIR指數為0,失敗組則高達0.03,整體預防組之PDIR指數為0.00992;而病歷回溯組之PDIR指數為0.0012。經分析後可發現預防成功組病患之CRII值顯著低於預防失敗組(0.42 vs. 0.98, p =0.014),但與病歷回溯組相較則無顯著差異(0.42 vs. 0.27, p =0.646);而預防失敗組之CRII值更是顯著高於病歷回溯組許多(0.98 vs. 0.27, p <0.001)。
本研究共由10名受試者之血液檢體取得15隻細菌,依生物膜生成實驗步驟得到每隻細菌所形成生物膜之吸光值,若吸光值越大,表示生物膜生成能力越強。但結果發現無論是依治療組與預防組、格蘭氏陽性菌與陰性菌、或是治療組成功與失敗區分,兩兩比較之生物膜生成能力皆無顯著差異。
由本研究結果仍無法得知生物膜生成能力對於抗生素封存療法成功或失敗之影響,但針對透析導管感染症,抗生素封存療法提供不拔除管路的病患另一選項,且也可有效控制感染,治療成功率達六成。
Arteriovenous fistulae (AVF) and graft (AVG) are preferred over hemodialytic catheters due to lower infection rate. It is almost not effective when using systemic antibiotic alone to treat catheter-related infection due to the biofilm formation. The biofilm protects microorganisms from antibiotics which cause recurrent infections. So the antibiotic-lock therapy (ALT) was developed; it means filling the catheters with high concentration antibiotics and lock for periods of time while the catheter is not in use. We’ve already known the fact that different microorganisms may affect the success rate of treatment, but we still want to know which factors, including biofilm formation ability, contribute to the treatment failure.
This is a prospective and retrospective study. The prospective groups recruited patients who were admitted to NCKUH from 2008.11.20 to 2009.5.15 due to suspicion of hemodialytic catheter-related bacteremia. We gave ALT to the treatment group for 3 weeks and to the prevention group for 2 weeks. And we collected blood cultures to evaluate the biofilm formation ability. For the retrospective group, we extracted clinical data from chart of hemodialytic patients who had been replaced catheters due to the suspicion of catheter-related infection. The data then compared with treatment group and prevention group.
We recruited 6 patients to treatment group. They all achieved the short-term treatment goal. And the success rate of long-term treatment was 66.7 %. There were another 16 patients to be recruited to prevention group. The success rate of prevention was 62.5 %. In retrospective group, there were 100 patients recruited, whom contributing to 130 infection episodes.
The main clinical sign of patients was fever. And there were 63.7% positive blood culture results, which contained 66.27 % GPC, 23.67 % GNB, and 10.06% fungi.
For the treatment groups, there were neither significant differences between the success and the failure groups nor between the success group and the retrospcetive group. But the success group had shorter hospitalized-days than retrospective group. (12.00 vs. 35.12 days, p = 0.04 ) The data between failure group and retrospective group had no differences. For the prevention groups, the systolic pressure (p = 0.047), the platelet(p = 0.036), and the hemoglobin (p = 0.030) level of success group were significant higher than retrospective group. Other data had no significant differences.
We conduct the index of patient-days infection rate (PDIR) and catheter-related infection index (CRII) to determine the prevention effect. The high PDIR means higher probibility of infection. And the high CRII means the longer duration of antibiotics used. The PDIR of success group was zero and the failure group was 0.03, total PDIR was 0.00992. But the PDIR of retrospective group was 0.0012. The CRII of success group was significantly lower than the failure group (0.42 vs. 0.98, p =0.014) but not different to retrospective group (0.42 vs. 0.27, p =0.646). The CRII of failure group was significantly higher than retrospective group (0.98 vs. 0.27, p <0.001).
We got 15 bacteriae from patients to test the biofilm formation ability. But we found that there were no differences between each of the following matches : treatment group and prevention group, GPC and GNB, and finally, the success group and failure group of treatment.
Though the biofilm formation ability seems no effect on the success of ALT, ALT still provides another choice instead of replacing catheters to treat catheter-related infections effectively. The success rate reached 66%.
目錄
中文摘要 i
Abstract iii
誌謝 v
目錄 vii
表目錄 x
圖目錄 xi
Abbreviation xii
第一篇、 抗生素封存療法對於透析導管相關感染症 的治療與預防效果 1
第一章 緒論 1
第二章 文獻回顧 3
第一節 末期腎臟疾病與血液透析 3
第二節 台灣末期腎臟疾病流行病學之現況 4
第三節 血液透析與相關感染 5
第四節 抗生素封存療法(Antibiotic-lock therapy, ALT) 19
第三章 研究目的 21
第四章 研究方法 22
第一節 研究設計 22
第二節 研究流程 24
第三節 評估指標與定義 32
第四節 統計方法與工具 34
第五章 研究結果 40
第一節 收案對象及病患基本資料 40
第二節 透析導管相關感染症之臨床表現 44
第三節 治療組結果 47
第四節 預防組結果 52
第五節 生物膜生成能力 57
第六節 藥物不良反應 60
第六章 討論 61
第一節 透析導管相關感染 61
第二節 抗生素封存療法之成效 62
第三節 評估預防性使用抗生素封存療法成效之參數 64
第四節 生物膜生成能力評估 66
第五節 研究限制 67
第六節 未來研究方向 68
第七章 結論 69
第二篇、 臨床藥事服務 70
第一章 目的 70
第二章 方法 70
第三章 記錄方式 71
第四章 結果 73
第一節 藥事服務個案 73
第二節 藥物資訊提供 81
第五章 結語 87
參考文獻 88
附錄ㄧ 人體試驗委員會同意臨床試驗證明書 94
附錄二 受試者同意書 95
附錄三 生物安全委員會生物材料異動申請審查單 97
附錄四 研究計畫宣導單 98
附錄五 Naranjo score評分表 100

表目錄
表一 不同血液透析通路之併發症發生比例 7
表二 靜脈導管相關感染症之定義 12
表三 常見造成血液透析中央靜脈導管相關血流感染之菌株 14
表四 各類透析導管抗生素調劑方法 35
表五 病患基本資料 43
表六 透析導管相關感染症之臨床表現 45
表七 透析導管相關感染症之菌株 46
表八 治療組病患感染時生理變化與治療成效指標 50
表九 預防組病患納入研究時生理基準值與預防成效指標 55
表十 受試者檢體培養之菌株與對照組標準菌株之生物膜吸光值 59
表十一 治療組與預防組之生物膜吸光值 59
表十二 格蘭氏陽性菌與格蘭氏陰性菌之受測菌株生物膜吸光值 59
表十三 治療組成功與失敗病患之受測菌株生物膜吸光值 59
表十四 成大醫院臨床藥事服務個案記錄表 個案編號 72
表十五 臨床藥事服務介入個案數 73
表十六 臨床藥事服務種類及數量統計 73
表十七 藥物不良反應評估個案 80

圖目錄
圖一 導管上之側邊孔洞 (side-hole) 7
圖二 透析導管相關感染症之影響因子關係圖 13
圖三 具皮下隧道之中央靜脈導管感染相關之菌血症處置方式 15
圖四 細菌生物膜形成之發展模式 18
圖五 治療組病患納入前流程 26
圖六 治療組病患納入後之研究流程 26
圖七 預防組病患納入前流程 28
圖八 預防組病患納入後研究流程 28
圖九 院內網路住院藥局管理系統之疑義處方照會 71
圖十 臨床藥事服務介入原因 74
圖十一 臨床藥事服務介入個案之藥品統計 75
圖十二 臨床藥事服務介入後之結果 76
圖十三 臨床藥事服務介入目的 77
圖十四 臨床藥事服務之經濟考量 77
圖十五 高三酸甘油脂血症之治療藥物選擇 83
圖十六 C型肝炎建議治療期間 85
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