Can tailored antibiotic doses beat resistance in the sickest patients?

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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.