• Tim M J Ewoldt, Alan Abdulla, Wim J R Rietdijk, Anouk E Muller, Brenda C M de Winter, HunfeldNicole G MNGMDepartment of Intensive Care Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.Department Hospital Pharmacy, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands., Ilse M Purmer, Peter van Vliet, Evert-Jan Wils, Jasper Haringman, Annelies Draisma, Tom A Rijpstra, Attila Karakus, Diederik Gommers, Henrik Endeman, and KochBirgit C PBCPDepartment Hospital Pharmacy, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.Rotterdam Clinical Pharmacometrics Group, Rotterdam, The Netherlands..
• Department of Intensive Care Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. t.ewoldt@erasmusmc.nl.
• Intensive Care Med. 2022 Dec 1; 48 (12): 176017711760-1771.

PurposeIndividualising drug dosing using model-informed precision dosing (MIPD) of beta-lactam antibiotics and ciprofloxacin has been proposed as an alternative to standard dosing to optimise antibiotic efficacy in critically ill patients. However, randomised clinical trials (RCT) on clinical outcomes have been lacking.MethodsThis multicentre RCT, including patients admitted to the intensive care unit (ICU) who were treated with antibiotics, was conducted in eight hospitals in the Netherlands. Patients were randomised to MIPD with dose and interval adjustments based on monitoring serum drug levels (therapeutic drug monitoring) combined with pharmacometric modelling of beta-lactam antibiotics and ciprofloxacin. The primary outcome was ICU length of stay (LOS). Secondary outcomes were ICU mortality, hospital mortality, 28-day mortality, 6-month mortality, delta sequential organ failure assessment (SOFA) score, adverse events and target attainment.ResultsIn total, 388 (MIPD n = 189; standard dosing n = 199) patients were analysed (median age 64 [IQR 55-71]). We found no significant differences in ICU LOS between MIPD compared to standard dosing (10 MIPD vs 8 standard dosing; IRR = 1.16; 95% CI 0.96-1.41; p = 0.13). There was no significant difference in target attainment before intervention at day 1 (T1) (55.6% MIPD vs 60.9% standard dosing; p = 0.24) or at day 3 (T3) (59.5% vs 60.4%; p = 0.84). There were no significant differences in other secondary outcomes.ConclusionsWe could not show a beneficial effect of MIPD of beta-lactam antibiotics and ciprofloxacin on ICU LOS in critically ill patients. Our data highlight the need to identify other approaches to dose optimisation.© 2022. The Author(s).

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