2011-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/647853摘要：加護病房中的感染症以革蘭氏陰性菌為主，乙內醯胺（beta-lactam）類為治療時的重要抗生素之一，但近年來抗藥性比例增加，使抗生素的選擇嚴重受限。若依beta-lactam類之『時間依賴型』藥效學特性，延長靜脈輸注時間以提高藥物血中濃度大於最小抑菌濃度（MIC）的時間（% T>MIC），將能最佳化殺菌效果，是對抗與避免抗藥性的策略之一，惟在臺灣仍不是常規處置。國際上有許多以藥效/藥動學模式模擬最適劑量的研究，歐美多所醫院已將這些研究結果應用在臨床治療，給藥時依腎功能調整劑量，也極少引起痙攣等嚴重副作用。但重症病人的藥動學參數可能與常人不同；文獻中依『藥效/藥動學模式』輸注藥物實際上造成的藥物血中濃度、MIC、臨床療效、安全性之間的關係，也缺乏足夠的實證與相關性。加上華人在加護病房中使用beta-lactam的藥動學文獻少，因此本研究將針對piperacillin/tazobactam、ceftazidime、cefepime、imipenem/cilastatin及meropenem五藥，以四年時間（每年研究一～二個上述抗生素）分析至少200位臺大醫院加護病房中革蘭氏陰性菌菌血症或肺炎成年病人之藥物血中濃度、致病菌MIC，療效及安全性。病人隨機分派到實驗組（延長輸注時間）或對照組（依院內治療指引），各藥各組均至少有20位病人。研究結果將提供藥動/藥效學與臨床治療實證，建立適合國人使用之抗生素療法。<br> Abstract: Gram-negative bacteria, including Acinetobacter baumannii, Pseudomonas aeruginosa,Enterobacteriaceae, are the major pathogens in intensive care units (ICU) worldwide. Theimportant role of beta-lactam antibiotics has been emphasized for their excellent safety andefficacy profiles. Unfortunately, the increasing resistance in Gram-negative bacteria has beena major challenge for healthcare professionals due to limited options of antimicrobial agentsavailable. Beta-lactam antibiotics exhibit “time-dependent” bactericidal activities againstsusceptible pathogens. For them, the time of the antibiotic concentration remaining above theminimal inhibitory concentration (MIC) is the strongest predictor for treatment success.Therefore, we may increase dose or frequency of beta-lactam antibiotics to obtain better%T>MIC, thus to overcome resistance. However, the approaches may result in undesired sideeffects, i.e., seizure or decreasing blood cell counts. An alternative method such as extendingthe duration of drug administration may be a superior option because it improvespharmacokinetic (PK) and pharmacodynamic (PD) characters compared to conventionaladministration duration with the PK/PD simulation model in the literatures. Growing numberof hospitals in Western countries have officially adopted extended infusion as a standard fortreatment, but this kind of treatment modality is still uncommon in Taiwan. There are alsovery few publications indicating PK data of piperacilin/tazobactam, ceftazidime, cefepime,imipenem/cilastatin, and meropenem in Asian patients in intensive care units. Furthermore,the association between dosing regimen suggested by PK/PD modeling and actual plasmaconcentration is lacking, and clinical outcome studies of extended infusion of beta-lactams inICU patients are very limited.The purpose of this study is to evaluate the PK/PD parameters, safety and efficacy ofextended infusion of piperacilin/tazobactam, ceftazidime, cefepime, imipenem/cilastatin, andmeropenem in at least 120 intensive care patients who are infected with Gram-negativebacteremia or pneumonia at National Taiwan University Hospital (NTUH). A four year studywill be needed to fully complete the data collection and analysis. Eligible patients will berandomly assigned to either study or control groups. Each group consists with at least 20patients who use one of the aforementioned antibiotics. The control group will follow thestandard (shorter) administration period based on NTUH antibiotic usage guidelines while thestudy group will receive prolonged infusion duration. All patients will have blood withdrawsafter the third dose for analysis of plasma concentration of free form antibiotics by using highperformance liquid chromatography (HPLC). We expect the study results will provide moreclinical data to confirm the appropriateness of extended infusion of beta-lactams in ICUpatients.contaminants of emerging concernendocrine disruptorsobesogenschildhood obesitypuberty development