分析vancomycin以Matzke method給藥其血中濃度範圍之適當性及影響因子

Analysis of Matzke Method for Vancomycin serum concentration and confounding factors

鄭淨黛(Ching-Tai, Cheng)

指導教授 ： 林双金

高雄醫學大學/藥學院/藥學研究所/碩士(2010年)

摘要

研究背景：
Vancomycin是屬於glycopeptide類的抗生素，廣泛用於治療葛蘭氏陽性細菌所造成的感染症，特別是methicillin-resistant Staphylococcus aureus。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。Vancomycin的經驗性給藥方法有相當多種，包含Moellering、Matzke與Rodvold等。而本研究將以內科加護病房成人病患為例，探討vancomycin以Matzke nomogram給藥後實際血中濃度範圍的適當性及影響血中濃度的因子。

研究方法：
本研究為單一中心的回溯性研究，從TDM資料檔收納2004年7月1日至2009年6月30日期間，使用vancomycin且由藥師訪視建議使用劑量的病患。收集其基本資料包含年齡、性別、實際體重、血清肌酸酐濃度(Scr)與vancomycin血中濃度等。病患腎臟功能評估採用Cockcroft-Gault公式。本研究排除vancomycin的給藥途徑為靜脈注射以外者、懷孕及哺乳婦女、嚴重燒燙傷(>10% BSA)病患與血液透析病患等。利用線性迴歸分析(linear regression analysis)來檢視藥物血中濃度和病患之年齡、實際體重、肌酸酐廓清率(CLcr)、起始劑量、維持劑量及給藥間隔等是否有相關性存在。

研究結果：
本研究族群430位病患的平均起始劑量與維持劑量分別為24.8±1.1 mg/kg與19.3 ± 1.1 mg/kg。病患資料經Cockcroft-Gault公式換算得CLcr ≧60 mL/min有242位(組I)、CLcr介於 30~60 mL/min有162位(組II)與CLcr 介於10~30 mL/min有26位(組III)。TDM結果顯示組I、II與III波峰濃度達到20~40 mg/L的百分比分別有80.2%、71.6%及88.5%，波谷濃度達到5~15 mg/L的百分比分別有62.0%、60.5%及69.2%，有大多數的波谷濃度比例(61.9%)可達到5-15 mg/L。使用ROC curve評估病患的血中濃度有較低的曲線下面積，波峰濃度之AUC值為0.501 (95%信賴區間0.392~0.611)，波谷濃度之AUC值為0.517 (95%信賴區間0.406~0.627)。以線性迴歸來檢視藥物血中濃度和病患CLcr有高度相關性存在。

結論：
研究顯示vancomycin以Matzke nomogram給藥後有高比例的波谷濃度可達到5~15 mg/L，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；另外，本研究也缺少與壯年人族群做比較。因此建議若是使用此方法作為經驗性給藥之依據，應該要進行藥物血中濃度監測，依據血中濃度資料再做進一步給予劑量及給藥間隔的調整。

關鍵字

vancomycin ； Matzke nomogram ； 藥物血中濃度監測 ； ROC曲線

並列摘要

Background
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. Several methods have been proposed for setting the initial dosage regimen of vancomycin therapy, including Moellering nomogram, Matzke nomogram and Rodvold etc.. By using the drug monitoring (TDM) data from adult MICU inpatients, this study had evaluated the appropriateness of the Matzke nomogram and tried to find confounding factor that influencing the vancomycin serum concemtration.

Methods
This is a single-center and retrospective study. All adult patients used vancomycin therapy and with TDM data from July 2004 to June 2009. Data was included in this population model dataset had been included in a previous population modelling study. Demographic data included patient age, gender, total body weight, serum creatinine (Scr) and serum concentrations were collected from TDM files. Creatinine clearance (CLcr) was calculated using the Cockcroft–Gault equation. Vancomycin using less than 48 hours or not using intravenous injection, pregnant or breast-feeding women, burn patients (>10%BSA) and patients on dialysis were excluded from the study. General demographic data with serum concentration and confounding factors were analyzed by linear regression analysis.

Results
The pharmacokinetics of vancomycin were characterized in 430 patients with different degrees of renal function after an initial dose of 24.8±1.1mg/kg and maintain dose 19.3 ± 1.1 mg/kg. According to the level of CLcr, there were 242, 162 and 26 patients subjects in CLcr > 60 mL/min (group I), 30~60 mL/min (group II) and 10~30 mL/min (group III), respectively. The results showed that peak level 80.2% patients in groups I, 71.6% patients in groups II and 88.5% patients in groups IIII were 20~40 mg/L; the trough level 62.0% patients in group I, 60.5% patients in groups II and 69.2% patients in groups IIII were 5~15 mg/L. When tested on Matzke method had the lowest area under the ROC curve, AUC 0.501 (0.392-0.611 95% C.I.) for peak level and AUC 0.517 (0.406-0.627 95% C.I.) for trough level, respeatively. The linear regression analysis showed that the ageing was the confounding favor in predicting vancomycin serum concentration.

Conclusions
Matzke nomogram was shown to achieve target plasma levels (5~15 mg/L) of vancomycin at a higher rate, but lack of convincing evidence of a correlation between serum concentrations and therapeutic outcome. Secondly, little comparative information is currently available as to the dosing of vancomycin in post-adolescent patient populations. This simulation indicated that the Matzke nomogram dosing interval was the most successful method for initial dose selection, but early serum concentration monitoring and adjustment of initial empirical and nomogram-derived doses is necessary.

並列關鍵字

vancomycin ； Matzke nomogram ； therapeutic drug monitoring (TDM) ； ROC curve

參考文獻

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