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

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

doi:10.1016/j.ijantimicag.2023.106931

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

Int J Antimicrob Agents. 2023 Oct;62(4):106931. doi: 10.1016/j.ijantimicag.2023.106931. Epub 2023 Jul 22.

Authors

Tim M J Ewoldt¹, Alan Abdulla², Wim J R Rietdijk³, Nicole Hunfeld⁴, Anouk E Muller⁵, Henrik Endeman⁶, Birgit C P Koch²; DOLPHIN study group

Affiliations

¹ Department of Intensive Care Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands; Rotterdam Clinical Pharmacometrics Group, Rotterdam, The Netherlands. Electronic address: t.ewoldt@erasmusmc.nl.
² Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands; Rotterdam Clinical Pharmacometrics Group, Rotterdam, The Netherlands.
³ Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁴ Department of Intensive Care Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁵ Rotterdam Clinical Pharmacometrics Group, Rotterdam, The Netherlands; Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Medical Microbiology, Haaglanden Medisch Centrum, The Hague, The Netherlands.
⁶ Department of Intensive Care Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.

PMID: 37482257
DOI: 10.1016/j.ijantimicag.2023.106931

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.

Keywords: Beta-lactam antibiotics; Ciprofloxacin; Critically ill; Model-informed; Precision dosing.