萬古黴素抗藥性Enterococcus faecium菌血症：抗生素治療結果以及死亡危險因子分析

Outcomes of Antimicrobial Treatment and Predictors of Mortality in Vancomycin-resistant Enterococcus faecium Bacteremia

陳盈宇(Ying-Yu Chen)

指導教授 ： 張上淳

國立臺灣大學/醫學院/臨床藥學研究所/碩士(2011年)

https://doi.org/10.6342/NTU.2011.02244

摘要

研究背景：
萬古黴素抗藥性Enterococcus faecium（vancomycin-resistant Enterococcus faecium，VREfm）菌血症之感染在近年來有上升的趨勢，而且臨床上能夠治療VREfm菌血症的藥物相當有限，因此在治療上格外地困難，然而目前對於VREfm菌血症之藥物治療結果以及病人預後相關之研究卻不多。

研究目的：
評估抗vancomycin-resistant enterococci（VRE）藥物之使用對於VREfm菌血症病人預後之影響，並進一步分析不同的抗生素對於VREfm菌血症之治療結果；另外也會分析VREfm菌血症發作後第30天之死亡危險因子。

研究設計、地點、對象：
本研究為單醫學中心之回溯性病歷分析，於國立臺灣大學醫學院附設醫院進行研究。研究對象為西元2009年1月1日至2010年12月31日感染VREfm菌血症之病人，只納入第一次感染事件，並排除年齡小於18歲及病歷資料不全者。

研究方法：
以紙本與電子病歷收集相關資料，包含病人基本資料、潛在疾病與造成菌血症感染之潛在因子、臨床表徵與相關檢驗數值、細菌培養結果、菌血症發作後之抗生素治療、後續追蹤與治療結果。本研究之主要觀察終點為菌血症發作後第30天之死亡率，並且利用單變項分析與多變項羅吉斯迴歸分析死亡危險因子以及抗生素治療對於病人預後之影響。

研究結果：
本研究共收入94位感染VREfm菌血症之成年病人，有93位（98.9%）病人為院內感染，有43位（45.7%）為單一菌種感染。全體病人之平均年齡為60.9±17.1歲，有57.4%為男性。在潛在疾病方面，以惡性腫瘤（62.8%）比例最高，其次為心血管疾病（55.3%）。在菌血症發作時，40.4%有敗血性休克，平均APACHE II score為 22.9±8.9。菌血症發作後第30天之死亡率在全體病人為55.3%，在單一菌種感染者則為48.8%。
在單一菌種感染方面，抗VRE藥物之使用對於其第30天之死亡率無顯著影響（P值0.67），而進一步分析不同抗生素之治療結果發現，linezolid組和daptomycin組在第30 天之死亡率也沒有達統計上顯著之差異（57.1% vs. 35.7%，P值0.26）。
在多變項羅吉斯迴歸分析中，全體病人於菌血症發作後第30天死亡之危險因子包含Charlson’s comorbidity index（勝算比1.47；95%信賴區間為1.12-1.93；P值0.006）、敗血性休克（勝算比3.13；95%信賴區間為1.08-9.05；P值0.0035）、APACHE II score≧23分（勝算比6.52；95%信賴區間為2.35-18.12；P值0.0003），而使用抗VRE藥物對於第30天之死亡率沒有影響（勝算比1.09；95%信賴區間為0.37-3.24；P值0.88）；單一菌種感染者於菌血症發作後第30天死亡之危險因子只有APACHE II score≧23分（勝算比14.15；95%信賴區間為2.63-75.98；P值0.002），但是Charlson’s comorbidity index較高者有較高之趨勢會死亡，雖然未達統計上之顯著差異（勝算比1.53；95%信賴區間為0.96-2.44；P值0.07），而抗VRE藥物之使用對於第30天之死亡也沒有顯著之影響（勝算比1.19；95%信賴區間為0.21-6.92；P值0.84）。

結論：
從全體病人或是單一菌種感染者的多變項分析結果顯示，病人於VREfm菌血症發作時之合併症以及疾病嚴重程度才是影響病人於菌血症發作後第30天死亡之危險因子，而使用抗VRE藥物治療VREfm菌血症並無法改善病人之預後。

關鍵字

抗生素治療 ； 菌血症 ； Enterococcus faecium ； 死亡率 ； 危險因子 ； 萬古黴素抗藥性

並列摘要

Background:
Vancomycin-resistant Enterococcus faecium (VREfm) bacteremia has increased rapidly in recent years. Because few agents have activity against VREfm, it is difficult to treat VREfm bacteremia. However, there were limited studies that analyzed treatment outcomes and prognosis of VREfm bacteremia.

Objectives:
The present study was performed to evaluate the influence of anti-VRE therapy on prognosis of VREfm bacteremia patients and treatment outcomes of different antibiotic regimens. Risk factors for 30-day mortality were also assessed.

Study design and study population:
A retrospective chart review was conducted at National Taiwan University Hospital (NTUH), a medical center in northern Taiwan. Patients with bacteremia due to VREfm between January 1, 2009 and December 31, 2010 were enrolled. Only the first episode of bacteremia for each patient was included in the analysis. Patients younger than 18 years old or with incomplete medical records were excluded.

Methods:
Data were collected from medical records, including demographic data, underlying diseases, predisposing factors for infection, clinical presentation at the onset of VREfm bacteremia, laboratory data, microbiological data, antimicrobial treatment and outcomes. The primary end point was 30-day all-cause mortality. Univariate and multivariate stepwise logistic regression analyses were performed to determine risk factors for mortality and outcomes of antimicrobial treatment.

Results:
Ninety-four patients were enrolled in this study, and ninety-three (98.9%) were nosocomial infection. Among patients with VREfm bacteremia, forty-three (45.7%) patients were monomicrobial infection. The mean age was 60.9±17.1 years old and 57.4% were men. The most common underlying diseases were malignancy (62.8%), followed by cardiovascular diseases (55.3%). At the onset of bacteremia, 40.4% had septic shock and the mean APACHE II score was 22.9±8.9. The 30-day mortality was 55.3% for all patients and was 48.8% for patients with monomicrobial infection.
Among patients with monomicrobial infection, receipt of anti-VRE therapy did not affect 30-day mortality (P=0.67). When further analyzing the treatment outcome between linezolid and daptomycin, there was no significant difference on 30-day mortality (57.1% vs. 35.7%，P=0.26).
Multivariate logistic regression of patients with VREfm bacteremia showed that Charlson’s comorbidity index (odds ratio 1.47, 95%CI 1.12-1.93, P=0.006), septic shock (odds ratio 3.13, 95%CI 1.08-9.05, P=0.0035), APACHE II score≧23 (odds ratio 6.52, 95%CI 2.35-18.12, P=0.0003) were independent risk factors for 30-day mortality, but anti-VRE therapy was not associated with 30-day mortality (odds ratio 1.09, 95%CI 0.37-3.24, P=0.88). Among patients with monomicrobial infection, multivariate logistic regression revealed that only APACHE II score≧23 was associated with 30-day mortality (odds ratio 14.15, 95%CI 2.63-75.98, P=0.002), and higher Charlson’s comorbidity index showed a trend towards higher mortality (odds ratio 1.53, 95%CI 0.96-2.44, P=0.07). However, anti-VRE therapy was not a significant risk factor for 30-day mortality (odds ratio 1.19, 95%CI 0.21-6.92, P=0.84).

Conclusions:
This study showed that severity of illness and comorbidity at the onset of VREfm bacteremia had a significant influence on prognosis of patients, but receipt of anti-VRE therapy did not improve survival for patients.

並列關鍵字

Antimicrobial treatment ； bacteremia ； Enterococcus faecium ； mortality ； risk factors ； vancomycin-resistant

參考文獻

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