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Efficacy of Carbapenems Compared With Noncarbapenem Broad-Spectrum Beta-Lactam Antibiotics as Initial Antibiotic Therapy Against Sepsis: A Nationwide Observational Study

碳青霉烯类与非碳青霉烯类广谱

β-内酰胺类抗生素作为脓毒症初始抗生素治疗的疗效比较：一项全国性观察研究

Background

As causative pathogens are not usually identified at the time of initiating antibiotics in sepsis, carbapenems are commonly used as an initial treatment. To reduce indiscriminate use of carbapenems, the efficacy of alternative empiric regimens, such as piperacillin–tazobactam and the fourth-generation cephalosporins, should be elucidated. This study aimed to evaluate survival effect associated with carbapenems as initial therapy for sepsis compared with these antibiotics.

背景

由于在开始使用抗生素治疗脓毒症时，通常无法确定致病病原体，因此碳青霉烯类药物通常被用作初始治疗。为了减少碳青霉烯类药物的滥用，应阐明其他经验性方案的疗效，如哌拉西林-他唑巴坦和第四代头孢菌素。本研究旨在评估碳青霉烯类抗生素作为脓毒症初始治疗的生存效果，并与这些抗生素进行比较。

Methods

This study was a multicenter retrospective observational study, used data of adult patients diagnosed as having sepsis from 2006 to 2019 extracted from a large-scale database in Japan. Patients were divided into two groups as follows: patients receiving carbapenems and patients receiving noncarbapenem broad-spectrum beta-lactam antibiotics as initial treatment. In-hospital mortality was compared between the groups by a logistic regression model adjusted by an inverse probability treatment weighting using propensity scores. To evaluate heterogeneity of effects according to patient characteristics, we also fitted logistic models in several subgroups. 

方法

这项研究是一项多中心回顾性观察研究，使用了从日本大规模数据库中提取的从2006年到2019年成人脓毒症患者的数据。将患者分为以下两组:接受碳青霉烯类抗生素的患者和接受非碳青霉烯类广谱β-内酰胺类抗生素作为初始治疗的患者。通过使用倾向评分的逆概率治疗加权调整的逻辑回归模型比较两组间的住院死亡率。为了根据患者特征评估效应的异质性，我们还在几个亚组中拟合了logistic模型。

Results

Among 7,392 patients with sepsis, 3,547 patients received carbapenems, and 3,845 patients received noncarbapenem agents. The logistic model showed no significant association between carbapenem therapy and lower mortality (adjusted OR 0.88, p = 0.108). Subgroup analyses suggested that there were significant survival benefits associated with carbapenem therapy in patients with septic shock, in ICUs, or with mechanical ventilation (p for effect modifications: < 0.001, 0.014, and 0.105, respectively).

结果

在7392例脓毒症患者中，3547例接受碳青霉烯类药物治疗，3845例接受非碳青霉烯类药物治疗。logistic模型显示碳青霉烯类药物治疗和低死亡率之间没有显著相关性(校正OR 0.88，p = 0.108)。亚组分析表明，碳青霉烯类药物治疗对感染性休克、ICU或机械通气患者有显著的生存益处(效应修正p值分别< 0.001、0.014和0.105)。
 

Conclusions

Compared with the noncarbapenem broad-spectrum antibiotics, carbapenems as initial empiric therapy were not associated with significantly lower mortality overall in patients with sepsis. Scientific evidence on the benefits of carbapenem therapy as initial therapy in sepsis is still limited, and further prospective studies need to be performed.

结论

与非碳青霉烯类广谱抗生素相比，碳青霉烯类抗生素作为初始经验性治疗并不显著降低脓毒症患者的总体死亡率。关于碳青霉烯类药物作为脓毒症初始治疗的益处的科学证据仍然有限，需要进行进一步的前瞻性研究。