TY - JOUR
T1 - Right dose, right now
T2 - bedside, real-time, data-driven, and personalised antibiotic dosing in critically ill patients with sepsis or septic shock—a two-centre randomised clinical trial
AU - Roggeveen, Luca F.
AU - Guo, Tingjie
AU - Fleuren, Lucas M.
AU - Driessen, Ronald
AU - Thoral, Patrick
AU - van Hest, Reinier M.
AU - Mathot, Ron A. A.
AU - Swart, Eleonora L.
AU - de Grooth, Harm-Jan
AU - van den Bogaard, Bas
AU - Girbes, Armand R. J.
AU - Bosman, Rob J.
AU - Elbers, Paul W. G.
N1 - Funding Information: The study was partially supported by a grant from the Netherlands Organisation for Health Research and Development (ZonMw, project number 836041018). The funders had no influence on the design and conduct of the trial, data collection and analysis of the results, writing of the manuscript or the decision to submit for publication. Publisher Copyright: © 2022, The Author(s).
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Background: 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. Methods: 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. Results: 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. Conclusions: 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.
AB - Background: 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. Methods: 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. Results: 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. Conclusions: 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.
KW - Clinical decision support
KW - Pharmacokinetics
KW - Sepsis
KW - Therapeutic drug monitoring
UR - http://www.scopus.com/inward/record.url?scp=85137252707&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s13054-022-04098-7
DO - https://doi.org/10.1186/s13054-022-04098-7
M3 - Article
C2 - 36064438
SN - 1364-8535
VL - 26
JO - Critical Care
JF - Critical Care
IS - 1
M1 - 265
ER -