全球對抗生素組合效用的評估困境

Abstract

細菌抗藥性是影響全球醫療體系的一大流行，目前臨床上常使用的療法包含 了抗生素組合，尤其是在治療多重抗藥性細菌上。然而，關於抗生素組合的療效是 有爭議的，近年來文獻上有支持的數據也有相反的，如此不一致的結論使「個人化」 抗生素組合顯的重要，要達到這個目標，在投藥前的評估即要做的完善。 在日本、台灣、和法國，我們透過拜訪微生物實驗室、檢驗室與感染科醫師來 了解當地如何去評估抗生素組合的效用，由於不同國家皆有自己習慣的一套判定 方式，由此得出一個結論—全球並沒有一個臨床評估抗生素組合效用的「黃金準 則」。僅有研究用的 E 測試法、棋盤格殺菌試驗、殺菌時間曲線試驗供參考用，而 此些實驗方法不單人力成本高，繁瑣的實驗流程更使其操作時間長，是此，這些研 究用的實驗方法始終無法完整被應用於臨床檢驗室。 為了解決此一痛點，我與三位共同創辦人們一起創立了醫流體股份有限公司， 以微流體的技術為核心去建造一抗生素篩選平台，不單能自動化的進行微量的抗 生素稀釋以及不同抗生素的混合、更能於 6 小時內給出抗生素敏感性結果。利用 在台大感染科實驗室實習的機會，以十例的臨床菌株驗證此微流體技術是否有辦 法準確的評估抗生素組合效用。

Antimicrobial resistance (AMR) is a well-known pandemic threating the modern medicine. To fight with AMR, antibiotic combination therapy (ACT) is commonly used in clinical practice, especially for treating multi-drug resistance bacteria. However, some recent studies demonstrated ACT has controversial results that some are supportive and some are not. This fact strengthens the importance that the use of ACT should be more individualized, and thus spotlights evaluating ACT effect before the actual prescription. In Japan, Taiwan, and France, we investigated how different countries evaluate ACT effect through laboratory practice, corporate visit, and consulting with infectious disease specialists. We confirmed that no gold standard methods have been established globally for the evaluation of ACT effect but for research use only, including the Etest methods, the checkerboard array, and the time-kill assay. It is the high labor cost and time- consuming procedure that make them cumbersome to adapt to the clinical labs. Aiming to tackle this issue, I cofounded MedFluid with my teammates and used microfluidic chip to build an antibiotic screening platform. The microfluidic chip can rapidly combine different antibiotics in multiple concentrations automatically and provide results within 6 hours. During my internship in the infectious disease laboratory at National Taiwan University Hospital, I validated the microfluidic chip with 10 clinical isolated bacteria to learn its functionality to evaluate the ACT effect.