內科加護病房克雷伯氏肺炎菌肺炎：流行病學調查與不同抗生素治療組合之有效性探討

Klebsiella pneumoniae Pneumonia in the Medical Intensive Care Units: Epidemiology and Effectiveness of Different Antibiotic Strategies

陳俞如(Yu-Ju Chen)

指導教授 ： 林英琦

高雄醫學大學/藥學院/藥學系臨床藥學碩士班/碩士(2018年)

摘要

研究背景
克雷伯氏肺炎菌是內科加護病房中最常見的病原菌之一，且其造成的高死亡率對於病人及醫療人員造成嚴重的威脅。此外，根據2017年台灣院內感染監視通報系統統計分析報告，克雷伯氏肺炎菌是醫學中心加護病房中最常分離的肺炎病原菌。因此，此研究的目的在於：一、分析造成克雷伯氏肺炎菌肺炎死亡的危險因子；二、探討何種抗生素治療對於克雷伯氏肺炎菌肺炎有較好的療效。

研究方法
這是一項在高醫附院、小港及大同的內科加護病房進行的回溯性觀察研究，利用高雄醫學大學的研究資料庫及病歷回溯的方式蒐集資料，探討於2009至2015年間之克雷伯氏肺炎菌造成之感染的分布，以及影響克雷伯氏肺炎菌肺炎加護病房死亡率的危險因子。此外，我們更進一步分析抗生素治療對於克雷伯氏肺炎菌肺炎的有效性。此研究以加護病房死亡率作為主要的分析結果，使用單變相及多變相的羅吉斯回歸來分析造成死亡率的危險因子及各種抗生素策略的有效性。

研究結果
研究期間共有416例患者感染肺炎，死亡率為37.3％。在多變項羅吉斯回歸模型中，肺炎合併菌血症 (aOR, 4.30; 95% CI, 2.17-8.50; P < .0001) ，先前使用免疫抑製劑 (aOR, 3.67; 95% CI, 1.32-10.20; P =0.0126)及APACHE II score (aOR, 1.05; 95% CI, 1.02-1.08; P =0.0007) 顯著增加ICU死亡率；Glasgow coma scale (aOR, 0.88; 95% CI, 0.82-0.95; P = 0.0004)及血小板計數 (aOR, 0.997; 95% CI, 0.995-0.999; P = 0.0027)為減少ICU死亡率的因子。關於抗生素分析，使用tigecycline做為確切性抗生素治療則與加護病房的死亡率顯著相關 (aOR，5.01; 95％CI，1.05-23.84; P =0.0427)。此外，penicillin-based和3rd or 4th cephalosporin-based的抗生素的有效性沒有差異。

結論
肺炎是我們病人族群中最常見的感染部位，肺炎合併菌血症以及先前使用免疫抑製劑會顯著增加死亡率。至於抗生素分析，確切性抗生素tigecycline在加護病房病人族群中死亡率最高。本研究提供克雷伯氏肺炎菌引起的肺炎之治療依據。

關鍵字

克雷伯氏肺炎菌 ； 肺炎 ； 加護病房

並列摘要

Background
K. pneumoniae is one of the most common pathogens in medical ICUs, and the high mortality rate poses a threat to the medical care professionals and patients. According to the report of the Taiwan Nosocomial Infections Surveillance System in 2017, K. pneumoniae is the most frequently isolated pathogen in pneumonic patients of ICUs in the medical centers. Therefore, our study has two aims: The first, to find the risk factors of mortality related to K. pneumoniae pneumonia of ICU patients. The second, find a better antibiotic regimen for patients infected with K. pneumoniae pneumonia who admitted to medical ICU.

Methods
This is a retrospective observational study conducted in medical intensive care units (MICU) of three hospitals affiliated to Kaohsiung Medical University. Patients with K. pneumoniae pneumonia admitted to MICU during January 2009 to December 2015 who met the inclusion criteria would be selected from the Research Database of KMU. Their clinical data would be collected from their electronic medical records. The primary clinical outcome in our study was ICU mortality. To access the risk factors for ICU mortality and the effectiveness of different antibiotic strategies, adjusted odds ratios (aORs) and 95% confidence interval (CIs) were acquired by multivariate analysis with logistic regression model.

Results
416 patients matched the inclusion and exclusion criteria and the mortality was 37.3%. In the multivariate logistic regression model, pneumonia complicated with bacteremia (aOR, 4.30; 95% CI, 2.17-8.50; P < .0001), prior use of immunosuppression agent (aOR, 3.67; 95% CI, 1.32-10.20; P =0.0126), and APACHE II score, (aOR, 1.05; 95% CI, 1.02-1.08; P =0.0007), Glasgow coma scale (aOR, 0.88; 95% CI, 0.82-0.95; P = 0.0004), platelet count (aOR, 0.997; 95% CI, 0.995-0.999; P = 0.0027), were significantly associated with ICU mortality. As for antibiotic analysis, tigecycline-based definitive therapy was significantly associated with higher ICU mortality (aOR, 5.01; 95％CI,1.05-23.84; P =0.0427). There was no difference in the effectiveness of penicillin-based and 3rd or 4th cephalosporin-based antibiotics.

Conclusion
Pneumonia was the most common infection site in our populations and pneumonia complicated with bacteremia and prior use of immunosuppression agent would significantly increase the mortality. As for antibiotic analysis, tigecycline-based definitive therapy was associated with the worst outcome. In the future, more studies are needed to confirm the effectiveness of antibiotic therapies in pneumonia caused by K. pneumoniae.

並列關鍵字

Klebsiella pneumoniae ； Pneumonia ； Intensive Care Units

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