Adequate antibiotic dosing may improve outcomes in critically ill patients but is challenging due to altered and variable pharmacokinetics. To address this challenge, AutoKinetics was developed, a decision support system for bedside, real-time, data-driven and personalised antibiotic dosing. This study evaluates the feasibility, safety and efficacy of its clinical implementation. In this two-centre randomised clinical trial, critically ill patients with sepsis or septic shock were randomised to AutoKinetics dosing or standard dosing for four antibiotics: vancomycin, ciprofloxacin, meropenem, and ceftriaxone. Adult patients with a confirmed or suspected infection and either lactate > 2 mmol/L or vasopressor requirement were eligible for inclusion. The primary outcome was pharmacokinetic target attainment in the first 24 h after randomisation. Clinical endpoints included mortality, ICU length of stay and incidence of acute kidney injury. After inclusion of 252 patients, the study was stopped early due to the COVID-19 pandemic. In the ciprofloxacin intervention group, the primary outcome was obtained in 69% compared to 3% in the control group (OR 62.5, CI 11.4–1173.78, p < 0.001). Furthermore, target attainment was faster (26 h, CI 18–42 h, p < 0.001) and better (65% increase, CI 49–84%, p < 0.001). For the other antibiotics, AutoKinetics dosing did not improve target attainment. Clinical endpoints were not significantly different. Importantly, higher dosing did not lead to increased mortality or renal failure. In critically ill patients, personalised dosing was feasible, safe and significantly improved target attainment for ciprofloxacin. Trial registration: The trial was prospectively registered at Netherlands Trial Register (NTR), NL6501/NTR6689 on 25 August 2017 and at the European Clinical Trials Database (EudraCT), 2017-002478-37 on 6 November 2017.

中文翻译：

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正确剂量，现在：在患有脓毒症或脓毒性休克的危重患者中进行床边、实时、数据驱动和个性化的抗生素给药——一项两中心的随机临床试验

足够的抗生素剂量可能会改善危重患者的预后，但由于药代动力学的改变和变化而具有挑战性。为了应对这一挑战，我们开发了 AutoKinetics，这是一种用于床边、实时、数据驱动和个性化抗生素给药的决策支持系统。本研究评估了其临床实施的可行性、安全性和有效性。在这项两中心随机临床试验中，患有败血症或感染性休克的重症患者被随机分配至 AutoKinetics 剂量或四种抗生素的标准剂量：万古霉素、环丙沙星、美罗培南和头孢曲松。确诊或疑似感染且乳酸 > 2 mmol/L 或需要血管加压药的成年患者符合入选条件。主要结果是随机分组后最初 24 小时内达到的药代动力学目标。临床终点包括死亡率、ICU住院时间和急性肾损伤的发生率。在纳入 252 名患者后，该研究因 COVID-19 大流行而提前停止。在环丙沙星干预组中，主要结果的获得率为 69%，而对照组为 3%（OR 62.5，CI 11.4-1173.78，p < 0.001）。此外，目标实现更快（26 小时，CI 18-42 小时，p < 0.001）和更好（增加 65%，CI 49-84%，p < 0.001）。对于其他抗生素，AutoKinetics 给药并未改善目标达到。临床终点没有显着差异。重要的是，更高的剂量不会导致死亡率或肾功能衰竭的增加。在危重患者中，个体化给药是可行的、安全的，并且显着提高了环丙沙星的达标率。试用注册：