延長β-lactam類抗生素輸注時間對抗菌力影響

Effect of Extended Infusion of β-lactam Antibiotics on Their Antibacterial Outcomes

β-lactam類抗生素因半衰期短，需要將一天劑量分三至四次給予，每次輸注時間約30～60分鐘，但β-lactam類抗生素屬時間依賴型抗生素，不需很高的波峰血中藥物濃度，而需血中藥物濃度長時間穩定且持續高於最小抑菌濃度（minimum inhibitory concentrations ,MIC），因此將輸注時間拉長，可優化抗生素在體內的藥物動力學，理論上可達到更優異的抗菌效果。許多研究針對不同的β-lactam類抗生素，比較同一抗生素延長輸注（prolonged infusion）與間歇輸注（intermittent infusion）的優劣，在眾多β-lactam類抗生素中，以piperacillin-tazobactam與carbapenems取得較多成果。可惜的是，目前發表的研究皆為小型前瞻性試驗或世代研究（cohort studies），並未有大型、高品質、隨機分派的研究可提供決定性證據，證實延長輸注相較傳統間歇輸注，可顯著地提升臨床治療效果。本文回顧過去相關的研究，分析新的給藥策略的優劣，並試圖找出可應用之處。

Given that β-lactam antibiotics have relatively short half-lives, they are required to be administered 3-4 times a day with each dose infused over 30-60 minutes. β-Lactam antibiotics are time-dependent, and do not need to reach peak blood concentrations. Rather, in order to ensure their antimicrobial effects, they are sustained over a long time at stable blood concentrations above the minimum inhibitory concentration (MIC). Therefore, prolonged infusion of β-lactam antibiotics might, theoretically, optimize their pharmacokinetics and help achieve more efficient antibacterial effects. Several studies have compared the effects of prolonged and intermittent infusions of different β-lactam antibiotics. Of these, piperacillin-tazobactam and carbapenems yielded better outcomes. Unfortunately, current published literature includes only either small prospective trials or cohort studies. Large and randomized control trials are required for conclusive evidence for whether prolonged or continuous infusion significantly improves clinical outcomes. In this article, we review the relevant literature and summarize conclusions.