內科加護病房碳青黴烯類抗藥性鮑氏不動桿菌肺炎:流行病學調查與不同抗生素治療組合之有效性探討

Carbapenem-Resistant Acinetobacter baumannii (CRAB) Pneumonia in the Medical Intensive Care Units: Epidemiology and Effectiveness of Different Anti-CRAB Antibiotic Strategies

梁君安(Chun-An Liang)

指導教授 ： 林英琦

共同指導教授 ： 許超群(Chau-Chyun Sheu)

高雄醫學大學/藥學院/藥學系臨床藥學碩士班/碩士(2017年)

摘要

研究背景
受限於有限的治療組合，鮑氏不動桿菌（Acinetobacter baumannii）造成的肺炎在加護病房病人有很高的死亡率。近年來碳青黴烯類抗藥性鮑氏不動桿菌（carbapenem-resistant Acinetobacter baumannii，CRAB）的比例逐年上升，但目前仍無好的實證證據支持最有效的治療方式為何。了解當地鮑氏不動桿菌的盛行率及抗藥性趨勢並採用最佳的抗生素組合因此為臨床重要的課題。因此本研究的目的為:一、高醫體系三院區院內及內科加護病房中常見菌種的流行病學探討，尤其是鮑氏不動桿菌的盛行率及藥物敏感性試驗趨勢；二、探討常用於治療CRAB肺炎中各藥物組合的有效性。
研究方法
本研究為一回溯性研究，利用高雄醫學大學研究資料庫與病歷回溯的方式，探討2010-2015年間高醫附院、小港及大同三院全院及內科加護病房的菌種及抗生素敏感性試驗的趨勢分析，並對內科加護病房內因CRAB造成的肺炎病人做各藥物組合的有效性探討。我們以加護病房死亡率做為主要的臨床結果。趨勢分析採用Cochran-Armitage test。在藥物有效性探討中，除了整體CRAB肺炎療效外，分成兩個族群探討：第一個族群是轉入內科加護病房時確診有CRAB肺炎的病人，第二個族群是於內科加護病房住院期間發生CRAB肺炎的病人。我們以單變項及多變項的羅吉斯回歸來分析整體及兩個族群中各種治療策略與加護病房死亡率之間的關聯性。
研究結果
在研究期間（2010-2015），總共有636位個案曾在內科加護病房中感染鮑氏不動桿菌，約占所有菌種的13%，位居加護病房中常見菌種的第三位。然而，這些個案中感染的鮑氏不動桿菌高達86%對carbapenem類抗生素有抗藥性，而此抗藥性的比例在院內有逐年上升的趨勢（p = 0.02）。在族群一（轉入加護病房時有CRAB肺炎的病人）和族群二（於加護病房住院中發生CRAB肺炎的病人）中各有112及103位病人納入最後分析。研究結果顯示，tigecycline最常作為治療藥物，約佔所有抗CRAB的抗生素中的71%，其次為colistin。結果顯示使用colistin有較低的死亡率（族群一：24.1%，p = 0.05；族群二：45.7%，p = 0.84）；相反的，使用tigecycline有較高的粗死亡率（族群一：39.5%，p = 0.05; 族群二，45.5%，p = 0.65）。進行多變項羅吉斯回歸發現，在所有CRAB肺炎病人中，單用tigecycline相較於使用非tigecycline類抗生素，會顯著增加加護病房死亡率（aOR, 2.05; 95% CI, 1.03-4.09），然而，單用colistin相較於採取colistin合併治療有較低的死亡率（aOR, 0.20; 95% CI, 0.02-0.68）。進一步將病人依幾個主要的治療組合區分時，我們發現單用colistin 比單用tigecycline能顯著降低加護病房死亡率（aOR, 0.25; 95% CI, 0.09-0.67）。
結論
鮑氏不動桿菌為加護病房中最常出現的菌種之一，CARB的比率仍逐年上升。本研究發現單用colistin相較於採取colistin合併治療能降低加護病房死亡率；相反的，使用tigecycline類抗生素相較於非tigecycline類抗生素會增加死亡率；在所有治療策略中，單用colistin相較單用tigecycline能顯著降低CRAB肺炎病人的加護病房死亡率。

關鍵字

碳青黴烯類抗藥性鮑氏不動桿菌 ； 肺炎 ； 抗生素 ； 加護病房 ； 死亡率

並列摘要

Background
The mortality of patients with pneumonia caused by Acinetobacter baumannii, especially carbapenem-resistant A. baumannii (CRAB), remains high. Due to limited therapeutic options, the rising prevalence of CRAB has become a threat in intensive care units (ICUs) worldwide. Building up the local antibiogram and finding the best anti-CRAB strategies are important issues. The aims of this study were: 1. to estimate the trends in the distribution and antibiotic susceptibility of A. baumannii, and 2. to evaluate the effectiveness of different anti-CRAB strategies in ICU patients with CRAB pneumonia.
Methods
This is a multicenter, retrospective study conducted in the medical intensive care units (MICUs) of three affiliated hospitals of Kaohsiung Medical University (KMU) in the southern Taiwan. Patients with pneumonia that were admitted into the MICUs between 2010 and 2015 were identified from the KMU research database and their medical records. ICU mortality was used as the primary outcome. A linear trend in the percent susceptibility of each antibiotic was assessed with the Cochran-Armitage test. To compare the effectiveness of anti-CRAB treatments, we estimated effectiveness in all CRAB pneumonia patients and two different cohorts. Patients admitted to the ICU with CRAB pneumonia were enrolled into cohort 1, and patients who developed CRAB pneumonia during the ICU stay were enrolled into cohort 2. Univariate and multivariate logistic regressions were used to evaluate the ICU mortality between different anti-CRAB strategies.
Results
Between 2010 and 2015, 636 ICU patients had A. baumannii infections, accounting for 13.0% of all isolations. The carbapenem-resistant rate of A. baumannii was up to 86% in the ICUs, and the resistant rate was significantly increasing (p = 0.02). We totally enrolled 215 patients in total and found that tigecycline was the most common antibiotic used for CRAB pneumonia. However, the tigecycline group had a higher crude ICU mortality rate of 39.5% in cohort 1 (p = 0.05) and 45.5% in cohort 2 (p = 0.65). Multivariate logistic regression found that tigecycline monotherapy was associated with higher ICU mortality compared to non-tigecycline therapy (OR, 2.05; 95% CI, 1.03-4.09). Colistin monotherapy was associated with lower ICU mortality than colistin combination therapy (aOR, 0.20; 95% CI, 0.02-0.68). We classified patients according to several treatment strategies, and found that colistin monotherapy was associated with lower ICU mortality than tigecycline monotherapy (aOR, 0.25; 95% CI, 0.09-0.67).
Conclusion
A. baumannii is common pathogen in the ICUs with high rate of resistance to carbapenem. Tigecycline-based was associated with higher ICU mortality than non-tigecycline based therapy. Among the anti-CRAB strategies, colistin monotherapy had lower ICU mortality than tigecycline monotherapy.

並列關鍵字

Carbapenem-resistant Acinetobacter baumannii ； Pneumonia ； Antimicrobial agents ； Intensive care unit ； Mortality

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