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脓毒症和脓毒性休克强化β-内酰胺类治疗24小时时的血清浓度:一项前瞻性研究:脓毒症中的β-内酰胺类血药浓度

Serum Concentration at 24 h With Intensive Beta-Lactam Therapy in Sepsis and Septic Shock: A Prospective Study: Beta-Lactam Blood Levels in Sepsis.

作者信息

Thériault Evelyne, Benali Massilia, Starnino Samuel, Blain Hugues, Goettel Nicolas, Beloin-Jubinville Bianca, Marsot Amélie, Lamontagne Francois

机构信息

Department of Pharmacy, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec, Canada.

Faculté de Pharmacie, Université de Montréal, Québec, Canada.

出版信息

Crit Care Res Pract. 2024 Oct 21;2024:9757792. doi: 10.1155/2024/9757792. eCollection 2024.

Abstract

Early administration of appropriate antibiotics has been shown to be among the most effective interventions to reduce mortality in septic patients. We evaluated the attainment of efficacy and safety targets at 24 h associated with the use of intensive beta-lactam therapy in patients admitted to the intensive care unit for sepsis. This was a prospective study with patients who received beta-lactams for sepsis or septic shock between February 2023 and September 2023. The antibiotic dose was unadjusted for renal function and administered by a loading dose followed by extended infusions, according to local practices. Blood samples were taken at the trough 24 h after the start of the beta-lactam to obtain serum levels. These levels were compared to efficacy and innocuity thresholds found in the literature. Among 36 included patients, all of them achieved serum concentrations above the minimum inhibitory concentration (MIC) for 100% of the therapeutic interval and 75% of them achieved serum concentrations above four times the MIC for 100% of the therapeutic interval. The predefined toxicity thresholds were reached by 8.3% of patients. Renal impairment was the factor most associated with the achievement of higher serum levels. Nonrenally adjusted doses of beta-lactams administered by extended infusion showed good attainment of effective concentrations and few toxic concentrations in critically ill patients with sepsis or septic shock. Further studies are needed to better define the association between toxic concentrations and toxicity manifestations.

摘要

早期使用适当的抗生素已被证明是降低脓毒症患者死亡率最有效的干预措施之一。我们评估了在因脓毒症入住重症监护病房的患者中,使用强化β-内酰胺类治疗在24小时时达到疗效和安全目标的情况。这是一项前瞻性研究,研究对象为2023年2月至2023年9月期间因脓毒症或脓毒性休克接受β-内酰胺类治疗的患者。根据当地的做法,抗生素剂量未根据肾功能进行调整,采用负荷剂量给药,随后进行延长输注。在β-内酰胺类药物开始使用24小时后的谷值时间采集血样以获得血清水平。将这些水平与文献中发现的疗效和无害性阈值进行比较。在纳入的36例患者中,所有患者在100%的治疗间期内血清浓度均高于最低抑菌浓度(MIC),75%的患者在100%的治疗间期内血清浓度高于四倍MIC。8.3%的患者达到了预定义的毒性阈值。肾功能损害是与达到较高血清水平最相关的因素。通过延长输注给予非肾调整剂量的β-内酰胺类药物,在脓毒症或脓毒性休克的重症患者中显示出良好的有效浓度达标率和较低的毒性浓度。需要进一步研究以更好地界定毒性浓度与毒性表现之间的关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1270/11519078/722ee2a763d6/CCRP2024-9757792.001.jpg

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