Abstract：
OBJECTIVE: To assess the mortality attributable to infections caused by carbapenem-resistant Enterobacterales (CRE) and to investigate the effect of clinical management on differences in observed outcomes in a multinational matched cohort study.
METHODS: A prospective matched-cohorts study (NCT02709408) was performed in 50 European hospitals from March 2016 to November 2018. The main outcome was 30-day mortality with an active post-discharge follow-up when applied. The CRE cohort included patients with complicated urinary tract infections, complicated intra-abdominal infections, pneumonia, or bacteraemia from other sources because of CRE. Two control cohorts were selected: patients with infection caused by carbapenem-susceptible Enterobacterales (CSE) and patients without infection. Matching criteria included type of infection for the CSE group, hospital ward of CRE detection, and duration of hospital admission up to CRE detection. Multivariable and stratified Cox regression was applied.
RESULTS: The cohorts included 235 patients with CRE infection, 235 patients with CSE infection, and 705 non-infected patients. The 30-day mortality (95% CI) was 23.8% (18.8-29.6), 10.6% (7.2-15.2), and 8.4% (6.5-10.6), respectively. The difference in 30-day mortality rates between patients with CRE infection when compared with patients with CSE infection was 13.2% (95% CI, 6.3-20.0), (HR, 2.57; 95% CI, 1.55-4.26; p < 0.001), and 15.4% (95% CI, 10.5-20.2) when compared with non-infected patients (HR, 3.85; 95% CI, 2.57-5.77; p < 0.001). The population attributable fraction for 30-day mortality for CRE vs. CSE was 19.28%, and for CRE vs. non-infected patients was 9.61%. After adjustment for baseline variables, the HRs for mortality were 1.87 (95% CI, 0.99-3.50; p 0.06) and 3.65 (95% CI, 2.29-5.82; p < 0.001), respectively. However, when treatment-related time-dependent variables were added, the HR of CRE vs. CSE reduced to 1.44 (95% CI, 0.78-2.67; p 0.24).
CONCLUSIONS: CRE infections are associated with significant attributable mortality and increased adjusted hazard of mortality when compared with CSE infections or patients without infection. Underlying patient characteristics and a delay in appropriate treatment play an important role in the CRE mortality.
METHODS: A prospective matched-cohorts study (NCT02709408) was performed in 50 European hospitals from March 2016 to November 2018. The main outcome was 30-day mortality with an active post-discharge follow-up when applied. The CRE cohort included patients with complicated urinary tract infections, complicated intra-abdominal infections, pneumonia, or bacteraemia from other sources because of CRE. Two control cohorts were selected: patients with infection caused by carbapenem-susceptible Enterobacterales (CSE) and patients without infection. Matching criteria included type of infection for the CSE group, hospital ward of CRE detection, and duration of hospital admission up to CRE detection. Multivariable and stratified Cox regression was applied.
RESULTS: The cohorts included 235 patients with CRE infection, 235 patients with CSE infection, and 705 non-infected patients. The 30-day mortality (95% CI) was 23.8% (18.8-29.6), 10.6% (7.2-15.2), and 8.4% (6.5-10.6), respectively. The difference in 30-day mortality rates between patients with CRE infection when compared with patients with CSE infection was 13.2% (95% CI, 6.3-20.0), (HR, 2.57; 95% CI, 1.55-4.26; p < 0.001), and 15.4% (95% CI, 10.5-20.2) when compared with non-infected patients (HR, 3.85; 95% CI, 2.57-5.77; p < 0.001). The population attributable fraction for 30-day mortality for CRE vs. CSE was 19.28%, and for CRE vs. non-infected patients was 9.61%. After adjustment for baseline variables, the HRs for mortality were 1.87 (95% CI, 0.99-3.50; p 0.06) and 3.65 (95% CI, 2.29-5.82; p < 0.001), respectively. However, when treatment-related time-dependent variables were added, the HR of CRE vs. CSE reduced to 1.44 (95% CI, 0.78-2.67; p 0.24).
CONCLUSIONS: CRE infections are associated with significant attributable mortality and increased adjusted hazard of mortality when compared with CSE infections or patients without infection. Underlying patient characteristics and a delay in appropriate treatment play an important role in the CRE mortality.
摘要：
目的：评估耐碳青霉烯类肠杆菌（CRE）感染引起的死亡率，并研究临床管理对多国配对队列研究中观察结果差异的影响。
方法：2016年3月至2018年11月在50家欧洲医院进行了一项前瞻性配对队列研究（NCT02709408）。主要结果是30天死亡率，出院后积极随访。CRE队列包括复杂尿路感染患者，复杂的腹腔感染，肺炎,或由于CRE而来自其他来源的菌血症。选择了两个对照组：碳青霉烯类敏感肠杆菌（CSE）引起的感染患者和未感染的患者。匹配标准包括CSE组的感染类型，CRE检测的医院病房，以及住院时间直至CRE检测。采用多变量分层Cox回归。
结果：队列包括235例CRE感染患者，235例CSE感染患者，705名未感染患者。30天死亡率（95%CI）为23.8%（18.8-29.6），10.6%（7.2-15.2），8.4%(6.5-10.6)，分别。与CSE感染患者相比，CRE感染患者30天死亡率差异为13.2%（95%CI，6.3-20.0），(HR,2.57；95%CI，1.55-4.26；p<0.001），与未感染患者相比，为15.4%(95%CI，10.5-20.2)(HR，3.85；95%CI，2.57-5.77；p<0.001)。CRE与30天死亡率的人口归因分数CSE为19.28%，和CREvs.未感染患者为9.61%.调整基线变量后，死亡率的HR分别为1.87(95%CI,0.99-3.50;p=0.06)和3.65(95%CI,2.29-5.82;p<0.001),分别。然而,当添加与治疗相关的时间依赖变量时，CRE的HR与CSE降至1.44（95%CI，0.78-2.67；p0.24）。
结论：与CSE感染或无感染患者相比，CRE感染与显著的归因死亡率和调整后死亡率增加相关。潜在的患者特征和适当治疗的延迟在CRE死亡率中起重要作用。
方法：2016年3月至2018年11月在50家欧洲医院进行了一项前瞻性配对队列研究（NCT02709408）。主要结果是30天死亡率，出院后积极随访。CRE队列包括复杂尿路感染患者，复杂的腹腔感染，肺炎,或由于CRE而来自其他来源的菌血症。选择了两个对照组：碳青霉烯类敏感肠杆菌（CSE）引起的感染患者和未感染的患者。匹配标准包括CSE组的感染类型，CRE检测的医院病房，以及住院时间直至CRE检测。采用多变量分层Cox回归。
结果：队列包括235例CRE感染患者，235例CSE感染患者，705名未感染患者。30天死亡率（95%CI）为23.8%（18.8-29.6），10.6%（7.2-15.2），8.4%(6.5-10.6)，分别。与CSE感染患者相比，CRE感染患者30天死亡率差异为13.2%（95%CI，6.3-20.0），(HR,2.57；95%CI，1.55-4.26；p<0.001），与未感染患者相比，为15.4%(95%CI，10.5-20.2)(HR，3.85；95%CI，2.57-5.77；p<0.001)。CRE与30天死亡率的人口归因分数CSE为19.28%，和CREvs.未感染患者为9.61%.调整基线变量后，死亡率的HR分别为1.87(95%CI,0.99-3.50;p=0.06)和3.65(95%CI,2.29-5.82;p<0.001),分别。然而,当添加与治疗相关的时间依赖变量时，CRE的HR与CSE降至1.44（95%CI，0.78-2.67；p0.24）。
结论：与CSE感染或无感染患者相比，CRE感染与显著的归因死亡率和调整后死亡率增加相关。潜在的患者特征和适当治疗的延迟在CRE死亡率中起重要作用。
