| 研究生: |
胡菩芳 Hu, Pu-Fang |
|---|---|
| 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 Effects of Antibiotic-lock Therapy on Dialytic Catheter-related Infections |
| 指導教授: |
高雅慧
Kao, Yea-Huei Yang |
| 學位類別: |
碩士 Master |
| 系所名稱: |
醫學院 - 臨床藥學研究所 Institute of Clinical Pharmacy |
| 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 infection, antibiotic-lock therapy, biofilm formation, antibiotic-lock solution |
| 相關次數: | 點閱:99 下載:3 |
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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%.
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