Resistance-Optimised Antimicrobial Dosing in Critically Ill Patients, a Randomised Controlled Trial

Critically ill adults who require mechanical ventilation commonly develophospital‐acquired respiratory infections. These infections are frequently treated withthe beta‐lactam antibiotics piperacillin/tazobactam or meropenem. Standard antibioticdosing may not always achieve drug levels that provide the best balance between treatinginfection and reducing the development of antibiotic resistance.The Resistance‐Optimised Antimicrobial Dosing in Critically Ill Patients RandomizedControlled Trial (ROAD‐RCT) is a multicentre, international, investigator‐initiated,open‐label, randomized, parallel‐group superiority trial. The study aims to determinewhether resistance‐optimised precision dosing improves clinical cure compared withstandard care dosing in mechanically ventilated critically ill adults withhospital‐acquired respiratory infections.A total of approximately 610 participants will be enrolled and randomized in a 1:1 ratioto one of two treatment strategies:Resistance‐optimised precision dosing guided by model‐informed precision dosing (MIPD).Standard care antibiotic dosing according to local clinical practice.Participants will receive treatment with either piperacillin/tazobactam or meropenem asprescribed by their treating clinical team. In the intervention group, dosingrecommendations will be supported by therapeutic drug monitoring (TDM), patient clinicalinformation, and dosing software to help achieve antibiotic exposure targets associatedwith suppression of antimicrobial resistance while remaining within accepted safetylimits. Participants assigned to standard care will receive antibiotic dosing determinedby their treating clinicians.The primary outcome is clinical cure at Day 14 after initiation of study antibiotictherapy.Secondary outcomes include time to clinical cure, mortality, treatment‐related adverseevents, duration of organ support therapies, emergence of antibiotic resistance,acquisition of new resistant microorganisms, hospital and intensive care unit length ofstay, quality of life, and health‐economic outcomes.Participants will be followed for up to 28 days after initiation of study antibiotictreatment.The study hypothesis is that resistance‐optimised precision dosing will improve clinicalcure while reducing the emergence of antimicrobial resistance compared with standard caredosing.The results of this study will provide evidence about the effectiveness, safety,feasibility, and potential scalability of precision antibiotic dosing strategies incritically ill patients with hospital‐acquired respiratory infections.