- 期刊
Piperacillin/tazobactam延長輸注與連續輸注方式給藥於重症病人臨床效益與安全性探討
Piperacillin/tazobactam Prolonged or Continuous Infusion in Critical Ill Patients: Clinical and Medical Economic Benefits
摘要
加護病房是最常使用抗生素的單位，而敗血症是使用抗生素的主要原因。敗血症也會影響抗生素藥物動力學變化，導致血中藥物濃度不足，使感染重症治療失敗機率上升。因此2016年敗血症治療指引建議，臨床醫師應根據藥物動力學採取不同的抗生素輸注策略，以提升敗血症治療成功率。β-lactam類抗生素中，piperacillin/tazobactam為最常用來對抗綠膿桿菌感染，屬於時間依賴型抗生素，可採取延長輸注4小時（prolonged infusion, PI）或者連續輸注24小時（continuous infusion, CI）這兩種策略。但PI、CI的輸注方式是否具有臨床上治療效益，或在不良反應發生率及醫療經濟成本上，具有不劣於甚至優於傳統輸注方式（CII）的優勢，值得進行文獻回顧。本文將探討以下三點：一、急重症病患病理生理變化與對抗生素藥物動力學之影響；二、使用PI、CI方式給與piperacillin/tazobactam對重症病患以及嗜中性血球低下發燒症（febrile neutropenia, FN）之效益探討；三、使用PI、CI方式給與piperacillin/tazobactam之安全性與醫療成本考量。結果發現，高疾病嚴重度的重症病患，使用PI、CI方式，可以提高血中藥物濃度，進而降低住院死亡率、治療天數以及抗生素暴露劑量以提高治療效益。其次，對於FN病患採PI、CI方式有較佳的臨床反應，尤其是已確認致病菌患者具有降低死亡率的優勢；第三，CI方式對於接受連續性血液透析替代療法（CRRT）的重症患者，可以提高血中藥物濃度，但不會增加急性腎損傷（AKI）的發生率；最後，CI、PI在醫療費用支出上，可顯著降低藥物的直接花費，甚至降低整體醫療照護支出費用。經由上述文獻，我們建議應推廣PI、CI在重症病患的使用，以達臨床及醫療經濟效益。
並列摘要
In sepsis, pharmacokinetic of antibiotics should be addressed as an important factor of treatment failure due to inadequate serum drug concentration. The current guideline in 2016 recommended adopting different infusion strategies of antibiotics to improve the treatment outcomes. Piperacillin/tazobactam, a time-dependent beta-lactam antibiotic, is commonly used to treat pseudomonas-related infection. Prolonged infusion (PI) for 4 hours or continuous infusion (CI) for 24 hours has been proposed to improve outcomes. Plenty of researches have been published regarding the comparison among PI, CI and conventional intermittent infusion (CII) in clinical efficacy,adverse effect, and economicbenefits. However, few comprehensive articles have been published in Chinese. The current article will focusing on three important issues : (1) Pathophysiology of acute critical ill patients (CIP) and its effect on antibiotic pharmacokinetics; (2) The benefits of using PI and CI strategy to administrate piperacillin/tazobactam to CIP or febrile neutropenia (FN); (3) The safety and economic benefits of using PI or CI strategy. Our review suggested that using PI or CI strategy in CIP with higher disease severity can increase drug concentrations in serum, thereby reducing the hospital mortality, total treatment days, and exposure dose of antibiotics to improve the therapeutic outcomes. PI or CI strategy in FN patients exist better treatment response, especially in those pathogens has been confirmed. The CI strategy could elevate the drug concentration during renal replace treatment and would not increase the incidence of acute kidney injury. Finally, we found the drug cost and total medical cost can significantly decrease by using of PI or CI strategy. In summary, we recommend PI or CI strategy in CIP to improve clinical efficacy and economic benefit in medical cost.