危重症脓毒症患者β-内酰胺血清浓度过高的神经学负担和结局：一项前瞻性队列研究。

Neurological burden and outcomes of excessive β-lactam serum concentrations of critically ill septic patients: a prospective cohort study.

机构信息

Department of Intensive Care Medicine, CHU Amiens-Picardie, Amiens, France.

Department of Clinical Pharmacology, CHU Amiens-Picardie, Amiens, France.

出版信息

J Antimicrob Chemother. 2023 Nov 6;78(11):2691-2695. doi: 10.1093/jac/dkad284.

DOI:10.1093/jac/dkad284

PMID:37694500

Abstract

BACKGROUND

Therapeutic drug monitoring (TDM) contributes to optimizing exposure to β-lactam antibiotics. However, how excessive exposure to β-lactams can increase the burden of care of critically ill patients is unclear.

PATIENTS AND METHODS

In a prospective cohort study, we examined whether excessive β-lactam serum concentrations contribute to neurological deterioration and the associated complications of adult septic patients without recent history of neurological disease treated with β-lactams in a medical ICU. Excessive β-lactam concentrations were defined as serum concentrations that exceeded the upper limit of the therapeutic range recommended by the French Societies of Pharmacology and Therapeutics (SFPT) and Anesthesia and Intensive Care Medicine (SFAR). Neurological deterioration was defined as an increase in the neurological Sequential Organ Failure Assessment score (nSOFA) of ≥1 between the day of starting treatment at admission and the day of TDM performed 2 days after treatment initiation.

RESULTS

We included 119 patients [median age: 65 years; males: 78 (65.5%)] admitted for acute respiratory distress [59 (49.6%)] or septic shock [25 (21%)]. In adjusted logistic regression analysis, an excessive β-lactam serum concentration was associated with neurological deterioration [OR (95% CI): 10.38 (3.23-33.35), P < 0.0001]. Furthermore, in adjusted linear regression analysis, an excessive β-lactam serum concentration was associated with longer time to discharge alive (β=0.346, P = 0.0007) and, among mechanically ventilated patients discharged alive, with longer time to extubation following the withdrawal of sedation (β=0.248, P = 0.0030).

CONCLUSIONS

These results suggest that excessive exposure to β-lactams could complicate the management of septic patients in the ICU and confirm the clinical relevance of the upper concentration limits recommended for dose reduction.

摘要

背景

治疗药物监测（TDM）有助于优化β-内酰胺类抗生素的暴露。然而，β-内酰胺类药物的过度暴露如何增加重症患者的护理负担尚不清楚。

患者和方法

在一项前瞻性队列研究中，我们研究了在没有近期神经病史的成年脓毒症患者中，β-内酰胺类药物治疗的 ICU 中，β-内酰胺类药物的血清浓度过高是否会导致神经恶化和相关并发症。β-内酰胺类药物的血清浓度过高被定义为血清浓度超过法国药理学和治疗学会（SFPT）和麻醉与重症监护医学学会（SFAR）推荐的治疗范围上限。神经恶化定义为在开始治疗的第一天和开始治疗后 2 天进行 TDM 之间，神经系统序贯器官衰竭评估评分（nSOFA）增加≥1 分。

结果

我们纳入了 119 名患者（中位年龄：65 岁；男性：78 例[65.5%]），急性呼吸窘迫[59 例（49.6%）]或感染性休克[25 例（21%）]入院。在调整后的逻辑回归分析中，β-内酰胺类药物血清浓度过高与神经恶化相关[比值比（95%CI）：10.38（3.23-33.35），P<0.0001]。此外，在调整后的线性回归分析中，β-内酰胺类药物血清浓度过高与存活出院时间延长相关（β=0.346，P=0.0007），且在存活并撤机的机械通气患者中，镇静剂停药后拔管时间延长（β=0.248，P=0.0030）。