Plasma Trough Concentrations of Beta-Lactam Antibiotics in the Early Phase of Septic Shock.

IF 2 4区医学 Q2 ANESTHESIOLOGY

Acta Anaesthesiologica Scandinavica Pub Date : 2025-07-01 DOI:10.1111/aas.70050

Malin Hägglund, Magnus Brink, Ulrika Snygg Martin, Daniel Bremell, Carl Johan Svensson

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Abstract

Introduction: Septic shock necessitates timely antibiotic therapy, often with broad-spectrum beta-lactam antibiotics (ß-LA). To our knowledge, no previous study has examined antibiotic concentrations repeatedly during the initial phase of treatment. This observational study aimed to assess early-phase plasma concentrations of ß-LA in patients with septic shock.

Method: Prospective observational study of patients with septic shock, according to the SEPSIS-3 criteria, who received cefotaxime, piperacillin/tazobactam, or meropenem in accordance with Swedish practice. Demographic and clinical data were recorded for each patient. Consecutive blood samples were obtained during the first 24 h of treatment, and total antibiotic concentrations were measured using liquid chromatography mass spectrometry. Target concentrations were defined as 100% of the time that free (unbound) antibiotic concentrations remained above the minimal inhibitory concentration (fT > MIC).

Results: Twenty-two patients were included, 15 (68%) were male and the median age was 65.5 years (IQR 46.3-65.5). In-hospital mortality was 7/22 (32%). Antibiotic exposure exceeding 100% fT > MIC was achieved in 16 (73%) of the patients. Four patients did not receive the recommended additional dose between the first and second doses of antibiotics; two of them still achieved 100% fT > MIC, whereas the other two attained 66% and 33% fT > MIC, respectively. Among the patients who received the additional dose, four did not achieve 100% fT > MIC. No relationship between mortality and fT > MIC was observed. Significant associations with achieving 100% fT > MIC were observed for older age (p = 0.045) and illness severity (SAPS3, p = 0.025).

Conclusion: Our findings demonstrate considerable variability in antibiotic exposure during the initial 24 h of septic shock treatment, highlighting a critical gap in understanding the clinical relevance of sub-optimal serum antibiotic concentrations and their potential impact on patient outcomes.

Editorial comment: Therapeutic drug monitoring of antimicrobials is increasingly being used in research and clinical practice.

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感染性休克早期β -内酰胺类抗生素的血浆谷浓度。

感染性休克需要及时使用抗生素治疗，通常使用广谱β -内酰胺类抗生素（ß-LA）。据我们所知，以前没有研究在治疗初期反复检查抗生素浓度。这项观察性研究旨在评估脓毒性休克患者早期血浆中ß-LA的浓度。方法：前瞻性观察研究，根据SEPSIS-3标准，根据瑞典惯例接受头孢噻肟、哌拉西林/他唑巴坦或美罗培南治疗的脓毒性休克患者。记录每位患者的人口学和临床资料。在治疗的前24小时内连续采集血液样本，并使用液相色谱-质谱法测定总抗生素浓度。目标浓度定义为游离（未结合）抗生素浓度保持在最低抑制浓度（fT > MIC）以上的100%时间。结果：纳入22例患者，男性15例（68%），中位年龄65.5岁（IQR 46.3 ~ 65.5）。住院死亡率为7/22（32%）。16例（73%）患者抗生素暴露超过100% fT > MIC。4名患者没有在第一次和第二次抗生素剂量之间接受推荐的额外剂量；其中两个仍然达到100%的fT > MIC，而另外两个分别达到66%和33%的fT > MIC。在接受额外剂量的患者中，有4名患者没有达到100% fT > MIC。死亡率与fT > MIC无关系。在年龄较大（p = 0.045）和疾病严重程度（SAPS3, p = 0.025）的患者中，达到100% fT > MIC有显著相关性。结论：我们的研究结果表明，在感染性休克治疗的最初24小时内，抗生素暴露具有相当大的可变性，突出了在了解次优血清抗生素浓度的临床相关性及其对患者预后的潜在影响方面的关键差距。编辑评论：抗微生物药物的治疗性药物监测越来越多地用于研究和临床实践。

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来源期刊

Acta Anaesthesiologica Scandinavica 医学-麻醉学

CiteScore

4.30

自引率

9.50%

发文量

157

审稿时长

3-8 weeks

期刊介绍： Acta Anaesthesiologica Scandinavica publishes papers on original work in the fields of anaesthesiology, intensive care, pain, emergency medicine, and subjects related to their basic sciences, on condition that they are contributed exclusively to this Journal. Case reports and short communications may be considered for publication if of particular interest; also letters to the Editor, especially if related to already published material. The editorial board is free to discuss the publication of reviews on current topics, the choice of which, however, is the prerogative of the board. Every effort will be made by the Editors and selected experts to expedite a critical review of manuscripts in order to ensure rapid publication of papers of a high scientific standard.