BACKGROUND Critically ill patients undergo extensive physiological alterations that will have impact on antibiotic pharmacokinetics. Up to 60% of intensive care unit (ICU) patients meet the pharmacodynamic targets of beta-lactam antibiotics, with only 30% in fluoroquinolones. Not reaching these targets might increase the chance of therapeutic failure, resulting in increased mortality and morbidity, and antibiotic resistance. The DOLPHIN trial was designed to demonstrate the added value of therapeutic drug monitoring (TDM) of beta-lactam and fluoroquinolones in critically ill patients in the ICU. METHODS A multi-centre, randomised controlled trial (RCT) was designed to assess the efficacy and cost-effectiveness of model-based TDM of beta-lactam and fluoroquinolones. Four hundred fifty patients will be included within 24 months after start of inclusion. Eligible patients will be randomly allocated to either study group: the intervention group (active TDM) or the control group (non-TDM). In the intervention group dose adjustment of the study antibiotics (cefotaxime, ceftazidime, ceftriaxone, cefuroxime, amoxicillin, amoxicillin with clavulanic acid, flucloxacillin, piperacillin with tazobactam, meropenem, and ciprofloxacin) on day 1, 3, and 5 is performed based upon TDM with a Bayesian model. The primary outcome will be ICU length of stay. Other outcomes amongst all survival, disease severity, safety, quality of life after ICU discharge, and cost effectiveness will be included. DISCUSSION No trial has investigated the effect of early TDM of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients. The findings from the DOLPHIN trial will possibly lead to new insights in clinical management of critically ill patients receiving antibiotics. In short, to TDM or not to TDM? TRIAL REGISTRATION EudraCT number: 2017-004677-14. Sponsor protocol name: DOLPHIN. Registered 6 March 2018 . Protocol Version 6, Protocol date: 27 November 2019.

中文翻译：

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β-内酰胺和氟喹诺酮类药物治疗药物监测对危重患者临床结局的影响：多中心随机对照试验的DOLPHIN试验方案。

背景技术重症患者经历广泛的生理改变，这将对抗生素药代动力学产生影响。多达60％的重症监护病房（ICU）患者达到了β-内酰胺类抗生素的药效学指标，而氟喹诺酮类药物仅占30％。未达到这些目标可能会增加治疗失败的机会，从而导致死亡率和发病率以及抗生素耐药性增加。DOLPHIN试验旨在证明ICU中危重患者中β-内酰胺和氟喹诺酮类药物的治疗药物监测（TDM）的附加价值。方法设计了多中心随机对照试验（RCT），以评估基于模型的TDM的β-内酰胺和氟喹诺酮类药物的疗效和成本效益。开始纳入后的24个月内将纳入450名患者。符合条件的患者将随机分配至两个研究组：干预组（活动性TDM）或对照组（非TDM）。在干预组中，在第1、3和5天根据T型进行研究抗生素（头孢噻肟，头孢他啶，头孢曲松，头孢呋辛，阿莫西林，阿莫西林与克拉维酸，氟氯西林，哌拉西林与他唑巴坦，美洛培南和环丙沙星的剂量调整）。贝叶斯模型。主要结果将是ICU住院时间。包括所有生存，疾病严重程度，安全性，ICU出院后生活质量以及成本效益等方面的其他结果。讨论没有试验研究过早期TDM对内危患者的β-内酰胺和氟喹诺酮类药物的临床效果。DOLPHIN试验的发现可能会为重症患者接受抗生素的临床治疗带来新的见解。简而言之，对TDM还是对TDM？试用注册EudraCT号：2017-004677-14。赞助商协议名称：DOLPHIN。2018年3月6日注册。协议版本6，协议日期：2019年11月27日。