研究背景
Vancomycin是一種可以用來治療因oxacillin-resistant Staphylococcus aureus (ORSA) 造成的感染症的抗生素。但是根據現有的一些研究報告指出，即使在體外試驗中ORSA對vancomycin呈現敏感性，臨床的治療效果會因為最低抑菌濃度 (minimum inhibitory concentration, MIC) 的不同而有所差別。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。

研究目的
本研究是以因ORSA造成的菌血症而使用vancomycin的病患為對象，評估vancomycin血中波谷濃度和最低抑菌濃度之比值與臨床療效的關係，同時評估vancomycin波谷濃度和腎毒性的相關性。

研究方法
本研究為前瞻性觀察研究，以民國九十五年一月二十日至七月三十一日間進入國立成功大學醫學院附設醫院住院且發生ORSA菌血症而使用vancomycin的成年病患且符合收案條件者為研究對象，記錄其開始使用vancomycin後第四天的波谷濃度、血液檢體細菌培養結果及第四、七、十一、十四日的常規生化、血液檢查數據、每日最高體溫和其他相關資料。主要評估指標為臨床治療效果及血中肌胺酸酐濃度變化。

研究結果
研究期間共有19位病患符合收案條件並納入分析。第四天的vancomycin血中波谷濃度與退燒情形有關，以波谷濃度大於或小於15 μg/mL分組，兩組於第四天已退燒的比例分別為85.7% 及33.3% (P = 0.05)；而第四天vancomycin波谷濃度與MIC比值與退燒情形無關，以比值大於或小於10分組，兩組於第四天已退燒的比例分別為77.8% 及30% (P = 0.07)。此外，19位病患中有5人的血中肌胺酸酐濃度變化符合腎毒性定義，但以有無發生腎毒性分組，兩組的平均vancomycin波谷濃度並無顯著差異。

結論
本研究顯示以vancomycin來治療ORSA菌血症患者時，較高的波谷濃度和第四天的退燒情形有相關性，此外，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波谷濃度無關，但仍需要更大規模的研究來佐證。

Background
Vancomycin is an antimicrobial agent used to treat infections caused by oxacillin-resistant Staphylococcus aureus (ORSA). According to the current literatures, however, even though the in vitro susceptibility of the ORSA strains to vancomycin, the clinical response may not be as good as expected because of the variation of minimum inhibitory concentration (MIC). Besides, nephrotoxicity is an adverse effct associated with vancomycin and it seems to be related to the trough concentration of vancomycin. But there is no definite conclusion and the native data in Taiwan is absent.

Objective
To evaluate the relationship between the ratio of vancomycin trough concentration to MIC of ORSA and the clinical outcome in hospitalized patients with ORSA bacteremia, and to assess the relationship between vancomycin trough concentration and nephrotoxicity.

Method
Adult patients admitted to National Cheng-Kung University Hospital during January 20, 2006 and July 31, 2006 and treated with vancomycin for ORSA bacteremia were eligible for this prospective observational study. On the fourth day after vancomycin use, vancomycin concentration was monitored and blood culture was repeated. Regular biochemistry and blood test on day 4, 7, 11, 14, daily highest temperatue and other associated data were collected. The primary endpoints are the clinical outcome and the change of serum creatinine concentration.

Results
Nineteen patients were enrolled during this period. On day 4, trough concentration of vancomycin was associated with the rate of defervescence. The afebrile rate were 85.7% and 33.3% among patients with trough level of above and below 15 μg/mL, respectively (P = 0.05). For the ratio of vancomycin trough concentration to MIC, patients with ratio greater than 10 had a trend of a higher defervescence rate in comparison with those with ratio less than 10 (77.8% vs. 30%, P = 0.07). In addition, nephrotoxicity was found in five patients, but the mean trough concentrations were not significantly different between the nephrotoxic and non-nephrotoxic groups.

Conclusions
The result of the study shows that higher serum vancomycin trough concentration is associated with the defervescence rate on day 4 when vancomycin is used to treat ORSA bacteremia. Besides, under the condition of regular therapeutic drug monitoring, the nephrotoxicity during vancomycin therapy doesn't seem to be associated with trough concentration, but it needs studies with large sample size to evaluate.

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