泌尿道感染病人使用喹諾酮類與主動脈瘤及主動脈剝離風險之關聯性：一個以臺灣人口為基礎的世代研究

Association between aortic aneurysm and aortic dissection with quinolone use in urinary tract infections patients: A population-based cohort study

陳尹陽(Yin-Yang Chen)

指導教授 ： 葉兆斌

共同指導教授 ： 周明智(Ming-Chih Chou)

中山醫學大學/醫學院/醫學研究所/碩士(2021年)

https://doi.org/10.6834/csmu202100141

摘要

研究目的
泌尿道感染是全世界最常見的社區型感染和院內感染。泌尿道感染的發生率會隨著年齡增加，且以女性為大宗。根據泌尿道感染治療指引的建議，頭孢子菌素和喹諾酮類為第一線的經驗性抗生素。然而過去研究指出喹諾酮類抗生素會造成主動脈瘤和主動脈剝離的風險上升，同時也有較新的研究指出主動脈瘤和主動脈剝離的風險會受到感染情形的干擾。因此本研究的目的為釐清泌尿道感染的病患使用喹諾酮類抗生素和主動脈瘤和主動脈剝離風險的相關性。

研究方法及資料
我們使用健保資料庫當中的2000年一百萬人承保抽樣歸人檔 (LHID2000)，納入從2002年1月1日至2016年12月31日當中有診斷為泌尿道感染並且只有使用單一種類抗生素的病患，再依據使用的抗生素分組別(喹諾酮類、第一/二代頭孢子菌素、第三代頭孢子菌素)。研究結果為主動脈瘤和主動脈剝離的診斷。我們使用多變數Cox迴歸分析來分析資料，並採用傾向分數配對來減少干擾因子造成的誤差。

研究結果
經過排除條件篩選後，總共有1249944位泌尿道感染的病患，而在PSM配對之後，有28568位病患使用喹諾酮類、28568位病患使用第一/二代頭孢子菌素及28568位病患使用第三代頭孢子菌素。女性為泌尿道感染的大宗。病患基礎資料及特徵如性別、年齡、合併症等在PSM之後在三組間沒有顯著差異。我們發現使用第三代頭孢子菌素的泌尿道感染病患與使用喹諾酮類相比，其主動脈瘤及主動脈剝離的風險有顯著但些微的上升(校正後風險比為1.59、95%CI =1.11-2.26、競爭型風險比為1.49 、95% CI=1.05-2.11)。Kaplan–Meier curve顯示使用第三代頭孢子菌素的泌尿道感染病患與使用喹諾酮類相比，反而有較高顯著的死亡率(Log-rank p<0.0001)和些微的主動脈瘤及主動脈剝離累積發生素上升(Log-rank p=0.2459)。
結論與建議
喹諾酮類的使用和第三代頭孢子菌素，對於泌尿道感染的病人並不會造成主動脈瘤及主動脈剝離的風險上升。如此風險的差異主要歸因於感染嚴重程度的不同。因此，臨床上對於泌尿道感染的病患，首要的目標為選擇合適的抗生素及針對感染的控制，而不是因為擔心主動脈瘤及主動脈剝離的風險而不使用喹諾酮類抗生素治療病患。

關鍵字

泌尿道感染 ； 主動脈瘤 ； 主動脈剝離 ； 喹諾酮類抗生素

並列摘要

Objective
Urinary tract infections(UTIs) are the most common community-acquired infections and hospital-acquired infection worldwide. The prevalence of UTIs increases with age and predominates in female compared with males. According to the current treatment guideline, antimicrobial regimen of Cephalosporin and Fluoroquinolone are the first-line antibiotics recommended for infection control. Recent studies have shown the positive association between aortic aneurysm/aortic dissection(AA/AD) and Fluoroquinolone, while other studies the risk was confounded by infection itself. The objective of this study is to clarify the relationship between AA/AD and Fluoroquinolone in UTIs patients.
Material and Methods
We used the Longitudinal Health Insurance Database (LHID) 2000, which is a subset of the National Health Insurance Research Database (NHIRD), to include patients of UTIs with diagnosis and accepted only one category of antibiotics treatment between 2002 to 2016. The patient further categorized into three groups based on category of the antibiotics use. The study event was defined as the diagnosis of aortic aneurysm and aortic dissection. Multivariate analysis with a multiple Cox regression model was applied to analyze the data. Propensity score match(PSM) was further performed to reduce the bias due to confounding variables.
Results
A total of 1249944 patients were selected from LHID 2000, which include 28568 UTIs patients in each three group of Fluoroquinolone, 1st or 2nd generation cephalosporin and 3rd generation cephalosporin after PSM. The incidence of AA/AD was conversely increased in UTIs patients with 3rd generation cephalosporin, comparing with the fluoroquinolones: the adjusted HR (aHR) was 1.59 (95% CI=1.11-2.26) and competing HR was 1.49 (95% CI=1.05-2.11). Mortality was also increased in patients with 3rd generation cephalosporin, with aHR of 1.85 (95% CI= 1.76-1.95). The Kaplan–Meier curve showed a significant increase in mortality in the 3rd-cephalosporins group (Log-rank p<0.0001) but not in the cumulative incidence of AA/AD (Log-rank p=0.2459).

Conclusion and Suggestion
Our study result showed that fluoroquinolones use, compared with 3rd-cephalosporin, was not associated with increased risk of AA/AD in UTI patients. The different risk of AA/AD may mainly attribute to different disease severity for each patient. Therefore, for patients with UTIs and indicated for antibiotics treatment, the first goal is to treat and control infection with adequate antibiotics, rather than postpone or even exclude the treatment of fluoroquinolones in the concern of AA/AD.

並列關鍵字

Urinary tract infections ； Aortic aneurysm ； Aortic dissection ； Fluoroquinolone

參考文獻

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