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NCT07820501

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

Sponsor: The University of Queensland

View on ClinicalTrials.gov

Summary

Critically ill people who need a breathing machine often develop hospital-acquired lung infections. These infections are commonly treated with the antibiotics piperacillin/tazobactam or meropenem. However, standard antibiotic doses may not always provide the right drug levels to fully treat the infection or help prevent antibiotic resistance. The purpose of this study is to determine whether a resistance-optimized antibiotic dosing approach improves recovery compared with standard antibiotic dosing in critically ill adults with hospital-acquired respiratory infections. Participants will be randomly assigned to 1 of 2 groups: Resistance-optimized precision dosing - guided by therapeutic drug monitoring and dosing software. Standard care - antibiotic dosing used at the participating hospital. All participants will receive treatment with either piperacillin/tazobactam or meropenem as determined by their treating clinical team. The study will compare whether the precision dosing approach leads to better clinical recovery, reduces the development of antibiotic-resistant bacteria, and is safe for participants. Approximately 610 mechanically ventilated adults will be enrolled from intensive care units in multiple countries. Participants will be followed for up to 28 days after starting study antibiotic treatment.

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

610

Start Date

2026-11

Completion Date

2029-09

Last Updated

2026-09-15

Healthy Volunteers

Conditions

Hospital-acquired Pneumonia (HAP)Ventilator-Associated Pneumonia (VAP)Nosocomial Respiratory Infection Critical Illness

Interventions

BEHAVIORAL

Resistance-Optimised Precision Dosing

Participants assigned to the intervention group will receive piperacillin/tazobactam or meropenem using resistance-optimised precision dosing guided by model-informed precision dosing (MIPD). Dosing recommendations will be based on patient clinical characteristics and therapeutic drug monitoring results and are intended to achieve antibiotic exposure targets associated with suppression of antimicrobial resistance while remaining within established safety limits. Dosing will be reviewed and adjusted during treatment using MIPD recommendations.

BEHAVIORAL

Standard Care Dosing

Participants assigned to the standard care group will receive piperacillin/tazobactam or meropenem according to routine clinical practice at the participating site. Antibiotic dose, infusion duration, dosing interval, and dose adjustments will be determined by the treating clinical team. Therapeutic drug monitoring may be performed if it is part of usual care at the study site.

Inclusion Criteria: 1. The patient is ≥ 18 years of age. 2. The patient has been admitted to the hospital for ≥ 48 h or was discharged from a hospital within the preceding seven days and is currently admitted to the ICU. 3. The patient is intubated and mechanically ventilated. 4. The patient is diagnosed with a probable or definitive respiratory infection and exhibits at least one of the following clinical features: I. New onset or worsening pulmonary symptoms or signs: increase in volume and/or purulence of respiratory secretions, worsening of hypoxaemia requiring an increase in the FiO2 and/or need for acute changes in the ventilator support system to support oxygenation. II. Radiological findings deemed consistent with a respiratory infection. III. Clinical signs and symptoms of infection: fever \> 38 °C, leucocytosis, increase in acute phase reactants such as C-reactive protein or procalcitonin. 5. The patient has been commenced on empiric or targeted treatment with piperacillin/tazobactam or meropenem for the management of a respiratory infection, with an expected duration of treatment of \> 72 h. 6. Piperacillin/tazobactam or meropenem have been commenced in an ICU that participates in ROAD-RCT. 7. The patient has an appropriate arterial or venous access for blood sampling. Exclusion Criteria: 1. The patient is known or suspected to be pregnant. 2. The patient has a known allergy to piperacillin/tazobactam or meropenem. 3. The patient has a community-acquired respiratory infection or chemical pneumonitis in the context of bronchoaspiration. 4. The patient has received piperacillin/tazobactam or meropenem for more than 48 h. 5. The antimicrobial dose initiated empirically is \> 4 g daily for meropenem and \> 18 g daily (16 g piperacillin / 2 g tazobactam) for piperacillin/tazobactam (excluding the loading dose) in patients who are not receiving renal replacement therapy. 6. The antimicrobial dose initiated empirically is \> 18 g daily (16 g piperacillin / 2 g tazobactam) for piperacillin/tazobactam and \> 2 g daily for meropenem in patients receiving renal replacement therapy (Table 1). 7. The patient's death is deemed imminent and inevitable. 8. The patient has previously been enrolled in ROAD-RCT. 9. The patient is or has been enrolled in another antimicrobial clinical trial that may interfere with the intervention as determined by the study investigators. 10. The patient has a baseline (at ICU admission or enrolment) positive rectal and/or nasopharyngeal screening swab, or is known to have been colonised within the past 6 months, with any of the following beta-lactam-resistant Gram-negative microorganism(s): carbapenem-resistant Enterobacterales, P. aeruginosa with DTR or carbapenem-resistant A. baumannii complex. 11. There is a prior known or likely reason that the patient would not consent if they were able to be asked.

Clinical Research Directory

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

Summary

Key Details

Conditions

Interventions

Eligibility Criteria