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Abstract：
BACKGROUND: This study aimed to evaluate the different efficacies between monotherapy and combination therapy with ceftazidime/avibactam (CAZ/AVI) in treating carbapenem-resistant Klebsiella pneumoniae (CRKP) infection.
METHODS: We retrospectively analyzed observational multicenter data from 38 hospitals in China. Multivariate regression analysis was used to explore the association between combination therapy with CAZ/AVI and in-hospital mortality. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to validate our findings.
RESULTS: A total of 132 eligible patients were divided into CAZ/AVI combination therapy (n = 43) and monotherapy (n = 89) cohorts. Multivariate logistic regression showed that there was no statistically significant relationship between combination therapy and a lower risk of in-hospital mortality [odds ratio (OR) 0.907, 95% confidence interval (CI) 0.329-2.498, p = 0.850]. In the subgroup of critical patients who were in the intensive care unit (ICU) (OR 0.943, 95% CI 0.221-4.033, p = 0.937) or with sequential organ failure assessment (SOFA) ≥ 3 (OR 0.733, 95% CI 0.191-2.808, p = 0.650), CAZ/AVI combination therapy was not a lower risk factor for in-hospital mortality. Moreover, in the subgroup of patients using CAZ/AVI plus tigecycline (accounting for 46.5% in the combination therapy) compared with CAZ/AVI monotherapy, there was no statistical difference between the two groups in in-hospital mortality, nor in the subgroup of patients with CRKP-associated pneumonia.
CONCLUSIONS: Combination therapy (or CAZ/AVI combined with tigecycline) and monotherapy with CAZ/AVI had similar prognoses in patients with only CRKP infection (or CRKP-associated pneumonia), as well as in critically ill patients. Larger randomized controlled trials are warranted to confirm these findings.
METHODS: We retrospectively analyzed observational multicenter data from 38 hospitals in China. Multivariate regression analysis was used to explore the association between combination therapy with CAZ/AVI and in-hospital mortality. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to validate our findings.
RESULTS: A total of 132 eligible patients were divided into CAZ/AVI combination therapy (n = 43) and monotherapy (n = 89) cohorts. Multivariate logistic regression showed that there was no statistically significant relationship between combination therapy and a lower risk of in-hospital mortality [odds ratio (OR) 0.907, 95% confidence interval (CI) 0.329-2.498, p = 0.850]. In the subgroup of critical patients who were in the intensive care unit (ICU) (OR 0.943, 95% CI 0.221-4.033, p = 0.937) or with sequential organ failure assessment (SOFA) ≥ 3 (OR 0.733, 95% CI 0.191-2.808, p = 0.650), CAZ/AVI combination therapy was not a lower risk factor for in-hospital mortality. Moreover, in the subgroup of patients using CAZ/AVI plus tigecycline (accounting for 46.5% in the combination therapy) compared with CAZ/AVI monotherapy, there was no statistical difference between the two groups in in-hospital mortality, nor in the subgroup of patients with CRKP-associated pneumonia.
CONCLUSIONS: Combination therapy (or CAZ/AVI combined with tigecycline) and monotherapy with CAZ/AVI had similar prognoses in patients with only CRKP infection (or CRKP-associated pneumonia), as well as in critically ill patients. Larger randomized controlled trials are warranted to confirm these findings.
摘要：
背景：本研究旨在评估头孢他啶/阿维巴坦（CAZ/AVI）单药治疗和联合治疗对碳青霉烯耐药的肺炎克雷伯菌（CRKP）感染的不同疗效。
方法：我们回顾性分析了来自中国38家医院的多中心观察数据。多因素回归分析用于探讨CAZ/AVI联合治疗与住院死亡率之间的关系。进行倾向评分匹配（PSM）和治疗加权逆概率（IPTW）以验证我们的发现。
结果：总共132名符合条件的患者被分为CAZ/AVI联合治疗组（n=43）和单药治疗组（n=89）。多变量逻辑回归显示，联合治疗与住院死亡率风险降低之间没有统计学意义的关系[比值比（OR）0.907，95％置信区间（CI）0.329-2.498，p=0.850]。在重症监护病房（ICU）（OR0.943，95％CI0.221-4.033，p=0.937）或序贯器官衰竭评估（SOFA）≥3（OR0.733，95％CI0.191-2.808，p=0.650）的重症患者亚组中，CAZ/AVI联合治疗不是住院死亡率较低的危险因素。此外，在使用CAZ/AVI联合替加环素的患者亚组（在联合治疗中占46.5％）与CAZ/AVI单药治疗相比，两组住院死亡率无统计学差异,在CRKP相关性肺炎患者亚组中也是如此。
结论：联合治疗（或CAZ/AVI联合替加环素）和单独治疗CAZ/AVI在仅有CRKP感染（或CRKP相关性肺炎）的患者中具有相似的预后，以及危重病人。需要更大规模的随机对照试验来证实这些发现。
方法：我们回顾性分析了来自中国38家医院的多中心观察数据。多因素回归分析用于探讨CAZ/AVI联合治疗与住院死亡率之间的关系。进行倾向评分匹配（PSM）和治疗加权逆概率（IPTW）以验证我们的发现。
结果：总共132名符合条件的患者被分为CAZ/AVI联合治疗组（n=43）和单药治疗组（n=89）。多变量逻辑回归显示，联合治疗与住院死亡率风险降低之间没有统计学意义的关系[比值比（OR）0.907，95％置信区间（CI）0.329-2.498，p=0.850]。在重症监护病房（ICU）（OR0.943，95％CI0.221-4.033，p=0.937）或序贯器官衰竭评估（SOFA）≥3（OR0.733，95％CI0.191-2.808，p=0.650）的重症患者亚组中，CAZ/AVI联合治疗不是住院死亡率较低的危险因素。此外，在使用CAZ/AVI联合替加环素的患者亚组（在联合治疗中占46.5％）与CAZ/AVI单药治疗相比，两组住院死亡率无统计学差异,在CRKP相关性肺炎患者亚组中也是如此。
结论：联合治疗（或CAZ/AVI联合替加环素）和单独治疗CAZ/AVI在仅有CRKP感染（或CRKP相关性肺炎）的患者中具有相似的预后，以及危重病人。需要更大规模的随机对照试验来证实这些发现。
