臺灣博碩士論文加值系統

前言
抗藥性細菌增加是廣泛使用抗生素的結果，如何減低抗藥性細菌的增加是近代醫學上的一大挑戰。臨床上，細菌產生抗藥性的原因中，抗生素的藥物動力學(pharmacokinetic；PK)與藥效學(pharmacodynamic；PD)參數的改變是一重要因素。其中，對於時間依賴型(time–dependent)抗生素而言，藥物在血中濃度大於最小抑菌濃度的時間(T＞MIC)是決定治療效果的重要指標，此指標跟抗藥性細菌產生的關連性至今還未釐清。但抗生素給藥的輸注形式是影響藥物動力學與藥效學參數的重要因素之ㄧ。本研究是以抗生素meropenem為例，利用電腦模擬試算取得適當的給藥劑量，並探討不同形式的抗生素輸注時間 (即間歇性輸注與持續性輸注)，所產生抑制肛門 (anus) 與喉嚨 (throat) 細菌群 (flora) 改變的效應。
研究材料與方法
自2005年1月1日至2006年6月30日期間總共有215位病患申請使用meropenem治療。扣除不符收案條件或完成治療但採檢不完整案例，實際確定收案分配到group I (對照組) 間歇性輸注30分鐘組病患有55位，及group II (實驗組) 持續性輸注 3小時組有49位，所有病人均有採集到治療前與治療後的肛門與喉嚨swab (拭子)的細菌培養。
結果
經過每6小時靜脈輸注meropenem 500 mg治療14日後，在肛門GNB 細菌群 (flora) 部分，Enterobacteriaceae (腸桿菌科) 細菌群之總數與比例降低，但是glucose nonfermenter (葡萄糖非發酵性) 細菌升高。其細菌群下降的幅度在grou II 持續性輸注3小時組明顯大於group I 間歇性輸注30分鐘組。但相對於Enterobacteriaceae (腸桿菌科)，在group I與group II兩組的glucose nonfermenter (葡萄糖非發酵性細菌) 的細菌群總數與比例都是升高，而其中MDR (multiple drug reisitance)菌株上升量尤其驚人。在喉嚨GNB細菌群部份的變化，group I與group II兩組Enterobacteriaceae (腸桿菌科)細菌大量降低，甚至ESBL 菌株與inducible菌株均被壓縮到幾乎不存在，但對glucose nonfermenter (葡萄糖非發酵性) 細菌中之MDR菌株及Stenotrophomonas maltophila (嗜麥芽窄食單胞菌)仍見大量升高。

結論
本實驗中，meropenem給藥輸注時間延長 (持續性輸注3小時組)，確實會讓血中濃度超過最小抑菌濃度佔給藥間隔時間的比例(%T＞MIC) 變的較佳。Meropenem使用低劑量延長給藥輸注時間的治療方式，對於Enterobacteriaceae (腸桿菌科) 細菌的根除效果較好，且throat (喉嚨)部位的根除效果較anus (肛門)部位明顯。但是對於glucose nonfermenter (葡萄糖非發酵性) 細菌，包括MDR菌株及Stenotrophomonas maltophila的根除效果，使用低劑量是不足的，即使延長輸注時間也幫助不大。因此，對於難治的細菌或容易出現抗藥性細菌的感染，應依據藥物動力學與藥效學考量抗生素使用適當的劑量級注射時間方式是必要的。

Background
Meropenem, a broad-spectrum antibiotic of carbapenem, is active against both gram-positive and negative organisms. There were postulate that the way of administration may influence effect of the pharmacodynamics in bactericidal activity (%T＞MIC). However , the bactericidal activity is coherent between the high dosage (2000 mg) and low dosage (500 mg). In the view of cost effectiveness goal, choice the low dose 500 mg meropenem with correct administration way may a best priority of strategy.
Objectives
The aims of this study was to differentiated the pharmacodynamics between 3 hours infusion and 30 minutes infusion of 500 mg meropenem.
Materials and methods
This was open-randomized study, adults with ventilation in the intensive care had infection required antimicrobial agent treatment were randomized to receive 500 mg of meropenem every 6 hours by 3 hours or 30 minutes infusion for 2 weeks. Throat and anus swab cultures were obtained at baseline and at the end of study therapy and take culture to compare the change of throat and gut flora.
Endpoints：
Observations and comparison the change of throat and gut flora.
Result：
One hundred and four patients were randomized to receive 30 minutes (n=55) or 3 hours (n=49) infusion of meropenem. Throat and anus swab cultures of these patients were done before and after meropenem administration. The throat culture results of 30 minutes infusion group before and after meropenem use were Enterobacteriaceae (27/3)、ESBL-producing Enterobacteriaceae (12/0) and glucose-non-ferment gram-negative bacilli (GNFGNB) (30/31); 3 hours group were Enterobacteriaceae (23/0)、ESBL-producing Enterobacteriaceae (8/0) and GNFGNB (39/37). The anus culture results of 30 minutes infusion group before and after meropenem use were Enterobacteriaceae (53/48)、ESBL-producing Enterobacteriaceae (42/28) and GNFGNB (15/27); 3 hours group were Enterobacteriaceae (46/32)、ESBL-producing Enterobacteriaceae (38/16) and GNFGNB (12/20).
Conclusion：
3 hours infusion of meropenem 500 mg every 6 hours has more decreasing the colonization of Enterobacteriaceae, ESBL– producing Enterobacteriaceae strains and Amp C inducible strains in throat and anus than 30 minutes infusion.

目錄 I
附圖目錄 III
附表目錄 IV
中文摘要 1
英文摘要 4
第一章 前言 7
第一節 研究背景 7
抗藥性細菌 7
抗生素的藥物動力學與藥效學關係 18
時間依賴型抗生素 19
Meropenem 24
第二節 研究目的 39
第二章 研究方法 40
第一節 研究材料 40
病人收集條件 40
細菌檢體收集條件 43
第二節 研究設計 45
第三節 統計方法 48
第三章 研究結果 49
肛門GNB flora的改變 49
喉嚨GNB flora的改變 50
第四章 結論與討論 51
參考文獻 58

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