Which patients benefit from model-informed precision dosing of beta-lactam antibiotics and ciprofloxacin at the ICU?

Tim M.J. Ewoldt*, Alan Abdulla, DOLPHIN study group, Wim J.R. Rietdijk, Nicole Hunfeld, Anouk E. Muller, Henrik Endeman, Birgit C.P. Koch

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Objectives: Antibiotic dosing is not optimal in the ICU. Our recent trial investigated the effect of model-informed precision dosing (MIPD) of beta-lactam antibiotics and ciprofloxacin and showed no significant differences in clinical outcomes in all patients. This study aimed to identify subgroups of patients in which the MIPD of these antibiotics could be beneficial for clinical outcomes. Methods: We analysed data from the DOLPHIN randomized controlled trial, which compared MIPD to standard dosing of beta-lactam antibiotics and ciprofloxacin in 388 ICU patients. We divided patients into subgroups based on baseline characteristics and assessed the effect of MIPD on 28-day mortality, 6-month mortality, change in sequential organ failure assessment (delta-SOFA), and ICU length of stay (LOS). Results: We found a lower 28-day mortality in patients with a SOFA below 8 randomized to MIPD (OR 0.40; 95% CI 0.17–0.88). However, patients with a higher SOFA show an increased 28-day mortality (OR 1.94; 95% CI 1.07–3.59) in the MIPD group. ICU LOS was increased in patients receiving MIPD with a SOFA below 8 (IRR 1.36; 95% CI 1.01–1.83) and those receiving MIPD for ceftriaxone (IRR 1.76; 95% CI 1.24–2.51). Patients receiving a dose recommendation within 24 hours show a trend towards decreased ICU LOS (IRR 0.77; 95% CI 0.52–1.16) and higher delta-SOFA (estimate -1.19; 95% CI -2.98–0.60). Conclusions: ICU patients with a SOFA below 8 using MIPD had an increased ICU LOS but a lower 28-day mortality. Fast dose recommendations using MIPD of beta-lactam antibiotics and ciprofloxacin needs to be investigated in ICU patients.

Original languageEnglish
Article number106931
JournalInternational Journal of Antimicrobial Agents
Volume62
Issue number4
DOIs
Publication statusPublished - Oct 2023

Bibliographical note

Funding Information:
Funding: This work was supported by the Dutch Organization for Health Research and Development ZonMw [ Grant 848017008 ], Stichting de Merel, and Erasmus MC MRace Grant. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.


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