Vancomycin 於藥物治療濃度監測之使用評估

Drug Evaluation of Vancomycin in Therapeutic Drug Monitoring

蔡淑貞(Shu-Chen Tsai)

指導教授 ： 黃耀斌

高雄醫學大學/藥學院/藥學研究所碩士在職專班/碩士(2012年)

摘要

研究背景及目的：Vancomycin是屬於glycopeptide類的抗生素，廣泛用於治療革蘭氏陽性(G(+)) 細菌所造成的感染症，特別是methicillin-resistant Staphylococcus aureus (MRSA)。使用vancomycin時需監測其藥物血中濃度來避免副作用的產生並觀察臨床療效。此外，腎毒性是 vancomycin 相關的不良反應之一，研究也指出這可能和 vancomycin 的血中濃度有關，但這方面目前仍沒有一確切定論，也尚缺少台灣本地的資料。本研究之目的是以使用 vancomycin 且有監測血中濃度的病患為對象，評估 vancomycin 之 trough濃度和腎毒性的相關性。
研究方法：本研究為回溯性研究，收集民國2009年1月1日至2009年12月31日於高雄某教學醫院住院，因醫師判定需使用vancomycin治療的患者且監測vanocmycin血中濃度(包含peak及trough濃度)之住院病人，則初步納入為收案對象。透過該院TDM資料檔收納，取得病人病歷號、姓名，依此資料審閱病歷。
研究結果：收集2009年1月至12月所有使用vancomycin的住院病患共57人，作回溯性的分析。使用vancomycin的患者其年齡分佈65歲以上者佔了29.82%(17人)；在57人中，27人(47.37%)為腦部感染，15人(26.32%)為菌血症，有27人(47.37%)細菌培養符合SANFORD GUIDE中vancomycin建議治療之菌種，其中14人(24.56%)為MRSA。100 % 病人在使用vancomycin前，已做血清中肌酸酐(serum creatinine; Scr)的監測，而用藥後，92.98%的醫師會再次監測病患的Scr，分析本研究族群57位病人的資料，病人資料經Cockcroft-Gault公式換算得CLcr ≧50 mL/min有36位(組I)、CLcr介於 10~50 mL/min有20位(組II)與CLcr 小於10 mL/min有1位(組III)。TDM結果顯示組I、II與III trough濃度達到5~15 mg/L的百分比分別有40.35%、12.28%及0%。另外，8人(14.04%)在使用vancomycin後腎功能變差，懷疑可能為藥物濃度所引起的腎毒性併發症，分析病人基本資料，性別、年齡、有無抽菸喝酒、就診科別與腎毒性的關係 (P值分別為0.609、0.605、0.596、0.589、0.665)；有17.54%的病人一開使使用vancomycin劑量是超過熱病的建議劑量，但即使使用劑量都在建議範圍內其有無發生腎毒性比例與超過建議劑量相同(P=0.772) ；有52.63% trough 濃度落於建議範圍(5~15 mg/mL)，42.11% trough 濃度大15 mg/mL，分析濃度與腎毒性發生與否沒有相關性(P=0.773)，另外如考慮vancomcyin使用天數對腎毒性的影響，62.50% 發生腎毒性的病人使用vancomcyin小於14天(P=1)，所以vancomcyin使用天數與腎毒性發生與否沒有相關性，可能原因為收案數較少，相較於前述所提及相關研究的個案數都是上百人，本研究的個案數明顯偏少，所以可能因此看不出差異性。
結論: 在常規藥物濃度監測作業下使用 vancomycin 期間產生的腎毒性可能和其血中trough濃度與使用天數無關，但仍需要更大規模的研究來佐證。但對於臨床療效並未評估，因此達到理想藥物血中濃度與治療結果的相關性仍需要進一步研究檢視。

關鍵字

萬古黴素 ； oxacillin抗藥性之金黃色葡萄球菌 ； 治療藥物血中濃度監測 ； 波谷濃度 ； 腎毒性

並列摘要

Background and aim: The glycopeptide antibiotic vancomycin has been widely used in the treatment of gram-positive infectious diseases; especially those caused by methicillin-resistant Staphylococcus aureus (MRSA). In vancomycin therapy, plasma levels of vancomycin must be monitored to avoid side effects and obtain effective clinical responses in each individual. Furthermore, renal toxicity is side effect of vancomycin. In our research showed renal toxicity may be related with higher therapeutic serum level, but it was still uncertain result, and also there was lack of data in Taiwan. The aim of this study is to evaluate the patient use vancomycin in hospitalized with the TDM the relationship between vancomycin trough concentration and nephrotoxicity.
Methods: This is a single-center in Kaohsiung and retrospective study. All adult patients used vancomycin therapy and with TDM data from Jan 2009 to Dec 2009. Data was included in this population model dataset had been included in a previous population modelling study. Creatinine clearance (CLcr) was calculated using the Cockcroft–Gault equation. Vancomycin using less than 4 days or not using intravenous injection, and patients on dialysis were excluded from the study.
Results: The pharmacokinetics of vancomycin were characterized in 57 patients with different degrees of renal function. 100% Patients did serum creatinine test before vancomycin administered, and 92.98% rechecked it after vancomyhcin adminisetred. We analysis the relationship of the p’ts characteristics and nephrotoxicity. No relationship between sex, age, smoking, drinking and nephrotoxicity of vancomycin. Most patients’ Initial vancomycin dose were in recommended dose, There are 17.5% of patient whose vancomycin dose over recommended dose. The rate of initial vancomycin dose within recommended range was the same in three group of patient (patient with, without nephrotoxicity, patient without SCr data). But there were more patients with nephrotoxicity in the groups whose vancomycin were over recommended dose group, and in group without Scr data. We analysis the relationship of vancomycin trough level and nephrotoxicity. Only 52.6% patient’s vancomycin trough level was within therapeutic range, 42.1% patients’ vancomycin trough level were more 15mg/dl. The were no patient happened nephrotoxicity in the group of vancomycin below 5mg/dl. There were more patient with nephrotoxicity in the group of vancomycin trough level more 15mg/dl. There were 59% patients using vancomycin less than 14days. There were more patients with nephrotoxicity in group of vancomycin using less than 14days, about 62.5%.
Conclusions: The result of the study shows that under the condition of regular therapeutic drug monitoring, the nephrotoxicity during vancomycin therapy doesn’t seem to be associated with trough concentration days of vancomycin therapy, but it needs studies with large sample size to evaluate.

並列關鍵字

Vancomycin ； oxacillin-resistant Staphylococcus aureus (ORSA) ； Therapeutic drug monitoring (TDM) ； trough concentration ； nephrotoxicity.

參考文獻

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