Achievement of therapeutic antibiotic exposures using Bayesian dosing software in critically unwell children and adults with sepsis

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2024年3月13日

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Ming G. Chai,
Quyen Tu,
Menino O. Cotta,
Michelle J. Bauer,
Ross Balch,
Charles Okafor,
Tracy Comans,
Peter Kruger,
Jason Meyer,
Kiran Shekar,
Kara Brady,
Cheryl Fourie,
Natalie Sharp,
Luminita Vlad,
David Whiley,
Jacobus P. J. Ungerer,
Brett C. Mcwhinney,
Andras Farkas,
David L. Paterson,
Julia E. Clark,
Krispin Hajkowicz,
Sainath Raman,
Seweryn Bialasiewicz,
Jeffrey Lipman,
Brian M. Forde,
Patrick N. A. Harris,
Luregn J. Schlapbach,
Lachlan Coin,
Jason A. Roberts,
Adam D. Irwin

摘要

Purpose

Early recognition and effective treatment of sepsis improves outcomes in critically ill patients. However, antibiotic exposures are frequently suboptimal in the intensive care unit (ICU) setting. We describe the feasibility of the Bayesian dosing software Individually Designed Optimum Dosing Strategies (ID-ODS™), to reduce time to effective antibiotic exposure in children and adults with sepsis in ICU.

Methods

A multi-centre prospective, non-randomised interventional trial in three adult ICUs and one paediatric ICU. In a pre-intervention Phase 1, we measured the time to target antibiotic exposure in participants. In Phase 2, antibiotic dosing recommendations were made using ID-ODS™, and time to target antibiotic concentrations were compared to patients in Phase 1 (a pre–post-design).

Results

175 antibiotic courses (Phase 1 = 123, Phase 2 = 52) were analysed from 156 participants. Across all patients, there was no difference in the time to achieve target exposures (8.7 h vs 14.3 h in Phase 1 and Phase 2, respectively, p = 0.45). Sixty-one courses in 54 participants failed to achieve target exposures within 24 h of antibiotic commencement (n = 36 in Phase 1, n = 18 in Phase 2). In these participants, ID-ODS™ was associated with a reduction in time to target antibiotic exposure (96 vs 36.4 h in Phase 1 and Phase 2, respectively, p < 0.01). These patients were less likely to exhibit subtherapeutic antibiotic exposures at 96 h (hazard ratio (HR) 0.02, 95% confidence interval (CI) 0.01–0.05, p < 0.01). There was no difference observed in in-hospital mortality.

Conclusions

Dosing software may reduce the time to achieve target antibiotic exposures. It should be evaluated further in trials to establish its impact on clinical outcomes.