Right dose, right now: bedside, real-time, data-driven, and personalised antibiotic dosing in critically ill patients with sepsis or septic shock—a two-centre randomised clinical trial
Abstract 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 antibi...
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Critical Care |
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| Online Access: | https://doi.org/10.1186/s13054-022-04098-7 |
| _version_ | 1811273672132919296 |
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| author | Luca F. Roggeveen Tingjie Guo Lucas M. Fleuren Ronald Driessen Patrick Thoral Reinier M. van Hest Ron A. A. Mathot Eleonora L. Swart Harm-Jan de Grooth Bas van den Bogaard Armand R. J. Girbes Rob J. Bosman Paul W. G. Elbers |
| author_facet | Luca F. Roggeveen Tingjie Guo Lucas M. Fleuren Ronald Driessen Patrick Thoral Reinier M. van Hest Ron A. A. Mathot Eleonora L. Swart Harm-Jan de Grooth Bas van den Bogaard Armand R. J. Girbes Rob J. Bosman Paul W. G. Elbers |
| author_sort | Luca F. Roggeveen |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-12T23:03:28Z |
| format | Article |
| id | doaj.art-6a01424511e0433f9b3a6d071324f5c2 |
| institution | Directory Open Access Journal |
| issn | 1364-8535 |
| language | English |
| last_indexed | 2024-04-12T23:03:28Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Critical Care |
| spelling | doaj.art-6a01424511e0433f9b3a6d071324f5c22022-12-22T03:12:59ZengBMCCritical Care1364-85352022-09-0126111110.1186/s13054-022-04098-7Right dose, right now: bedside, real-time, data-driven, and personalised antibiotic dosing in critically ill patients with sepsis or septic shock—a two-centre randomised clinical trialLuca F. Roggeveen0Tingjie Guo1Lucas M. Fleuren2Ronald Driessen3Patrick Thoral4Reinier M. van Hest5Ron A. A. Mathot6Eleonora L. Swart7Harm-Jan de Grooth8Bas van den Bogaard9Armand R. J. Girbes10Rob J. Bosman11Paul W. G. Elbers12Department of Intensive Care Medicine, Laboratory for Critical Care Computational Intelligence (LCCCI), Amsterdam Medical Data Science (AMDS), Amsterdam Cardiovascular Science (ACS), Amsterdam Institute for Infection and Immunity (AI&II), Amsterdam UMC, Vrije UniversiteitDepartment of Intensive Care Medicine, Laboratory for Critical Care Computational Intelligence (LCCCI), Amsterdam Medical Data Science (AMDS), Amsterdam Cardiovascular Science (ACS), Amsterdam Institute for Infection and Immunity (AI&II), Amsterdam UMC, Vrije UniversiteitDepartment of Intensive Care Medicine, Laboratory for Critical Care Computational Intelligence (LCCCI), Amsterdam Medical Data Science (AMDS), Amsterdam Cardiovascular Science (ACS), Amsterdam Institute for Infection and Immunity (AI&II), Amsterdam UMC, Vrije UniversiteitDepartment of Intensive Care Medicine, Laboratory for Critical Care Computational Intelligence (LCCCI), Amsterdam Medical Data Science (AMDS), Amsterdam Cardiovascular Science (ACS), Amsterdam Institute for Infection and Immunity (AI&II), Amsterdam UMC, Vrije UniversiteitDepartment of Intensive Care Medicine, Laboratory for Critical Care Computational Intelligence (LCCCI), Amsterdam Medical Data Science (AMDS), Amsterdam Cardiovascular Science (ACS), Amsterdam Institute for Infection and Immunity (AI&II), Amsterdam UMC, Vrije UniversiteitDepartment of Pharmacy and Clinical Pharmacology, Amsterdam UMC, University of AmsterdamDepartment of Pharmacy and Clinical Pharmacology, Amsterdam UMC, University of AmsterdamDepartment of Pharmacy and Clinical Pharmacology, Amsterdam UMC, University of AmsterdamDepartment of Intensive Care Medicine, Laboratory for Critical Care Computational Intelligence (LCCCI), Amsterdam Medical Data Science (AMDS), Amsterdam Cardiovascular Science (ACS), Amsterdam Institute for Infection and Immunity (AI&II), Amsterdam UMC, Vrije UniversiteitDepartment of Intensive Care, OLVG HospitalDepartment of Intensive Care Medicine, Laboratory for Critical Care Computational Intelligence (LCCCI), Amsterdam Medical Data Science (AMDS), Amsterdam Cardiovascular Science (ACS), Amsterdam Institute for Infection and Immunity (AI&II), Amsterdam UMC, Vrije UniversiteitDepartment of Intensive Care, OLVG HospitalDepartment of Intensive Care Medicine, Laboratory for Critical Care Computational Intelligence (LCCCI), Amsterdam Medical Data Science (AMDS), Amsterdam Cardiovascular Science (ACS), Amsterdam Institute for Infection and Immunity (AI&II), Amsterdam UMC, Vrije UniversiteitAbstract 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.https://doi.org/10.1186/s13054-022-04098-7SepsisTherapeutic drug monitoringPharmacokineticsClinical decision support |
| spellingShingle | Luca F. Roggeveen Tingjie Guo Lucas M. Fleuren Ronald Driessen Patrick Thoral Reinier M. van Hest Ron A. A. Mathot Eleonora L. Swart Harm-Jan de Grooth Bas van den Bogaard Armand R. J. Girbes Rob J. Bosman Paul W. G. Elbers Right dose, right now: bedside, real-time, data-driven, and personalised antibiotic dosing in critically ill patients with sepsis or septic shock—a two-centre randomised clinical trial Critical Care Sepsis Therapeutic drug monitoring Pharmacokinetics Clinical decision support |
| title | Right dose, right now: bedside, real-time, data-driven, and personalised antibiotic dosing in critically ill patients with sepsis or septic shock—a two-centre randomised clinical trial |
| title_full | Right dose, right now: bedside, real-time, data-driven, and personalised antibiotic dosing in critically ill patients with sepsis or septic shock—a two-centre randomised clinical trial |
| title_fullStr | Right dose, right now: bedside, real-time, data-driven, and personalised antibiotic dosing in critically ill patients with sepsis or septic shock—a two-centre randomised clinical trial |
| title_full_unstemmed | Right dose, right now: bedside, real-time, data-driven, and personalised antibiotic dosing in critically ill patients with sepsis or septic shock—a two-centre randomised clinical trial |
| title_short | Right dose, right now: bedside, real-time, data-driven, and personalised antibiotic dosing in critically ill patients with sepsis or septic shock—a two-centre randomised clinical trial |
| title_sort | right dose right now bedside real time data driven and personalised antibiotic dosing in critically ill patients with sepsis or septic shock a two centre randomised clinical trial |
| topic | Sepsis Therapeutic drug monitoring Pharmacokinetics Clinical decision support |
| url | https://doi.org/10.1186/s13054-022-04098-7 |
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