Collaborative approach of individual participant data of prospective studies of de-escalation in non-immunosuppressed critically ill patients with sepsis

Background: There is a concern to conduct de-escalation in very sick patients. Aims: To determine if de-escalation is feasible in ICU settings. Methods: We performed a metaanalysis of published studies conducted comparing de-escalation (defined by withdrawal of at least one antimicrobial empirically prescribed, switch to a new antimicrobial with narrower spectrum and withdrawal of at least one antimicrobial plus change of another drug to a new one with narrower spectrum) in non-immunocompromised patients with sepsis admitted to ICU. Results: Eight hundred and seventeen patients with severe sepsis or septic shock were evaluated. De-escalation was applied in 274 patients (33.5%). We found no differences in hospital long of stay between de-escalation group compared to those who did not receive it. We also found significant lower hospital mortality in de-escalation group as compared with no modification group in front of the others (25.9 vs. 43.1%; p < 0.001). Taking into account the etiology of infection, in both gram negative and gram positives microorganisms, de-escalation strategy was assessed as a good prognosis factor for mortality in the adjusted multivariate analysis (OR 0.41; 95% CI 0.22–0.74 and OR 0.33; 95% CI 0.15–0.70 respectively) whereas SOFA score along with age were found as a factors independently associated with a worse clinical outcome (OR 1.23; 95% CI 1.12–1.35 and OR 1.02; 95% CI 1.01–1.04 respectively). Conclusions: In our study there was an independent association of de-escalation and decrease mortality rate.

背景：针对重症患者开展抗菌药物降阶梯治疗（de-escalation）的临床可行性已成为学界关注的议题。
研究目的：明确抗菌药物降阶梯治疗在重症监护室（Intensive Care Unit，ICU）中的应用可行性。
方法：本研究针对收入ICU的非免疫功能低下脓毒症患者，对已发表的相关研究开展荟萃分析，对比不同抗菌药物降阶梯治疗方案——该方案定义为以下三类：停用至少1种经验性开具的抗菌药物、换用窄谱新型抗菌药物，或停用至少1种抗菌药物并将另一种药物更换为窄谱新型抗菌药物。
结果：本研究共纳入817例重度脓毒症或感染性休克患者进行评估。其中274例（33.5%）患者接受了抗菌药物降阶梯治疗。研究未观察到降阶梯治疗组与非降阶梯治疗组患者的住院时长存在显著差异；与未调整抗菌药物治疗组相比，降阶梯治疗组的住院病死率显著更低（25.9% vs. 43.1%；p < 0.001）。按感染病原体分型分析，在革兰阴性菌与革兰阳性菌感染亚组中，经校正的多因素分析显示，抗菌药物降阶梯治疗策略均为患者病死率的良好预后因素（比值比（Odds Ratio，OR）分别为0.41、95%置信区间（Confidence Interval，CI）：0.22–0.74；0.33、95%CI：0.15–0.70）；而序贯器官衰竭评分（SOFA）与年龄则被证实为与不良临床结局独立相关的因素（OR分别为1.23、95%CI：1.12–1.35；1.02、95%CI：1.01–1.04）。
结论：本研究证实，抗菌药物降阶梯治疗与患者病死率降低存在独立相关性。