Table 3. Primary and secondary outcomes and outcome measures.

Outcome	Definition/outcome measure
Primary outcomes
Feasibility of recruitment	Enrolment of a sufficient number of eligible participants within the specified timeframe of the study (6 months).This will include: Monthly recruitment rates. Number of patients screened. Ratio of randomised to screened patients.
Feasibility and fidelity of TDM	The degree to which the test (TDM) is delivered as intended: Time from meeting eligibility to first TDM. Compliance with TDM: timing of sample collection, processing and result availability. Compliance with TDM-guided dosing per protocol: proportion of dose recommendations accepted and implemented by the treating clinical team.
Secondary outcomes
Target attainment	The proportion of days where 100% fT>MIC is attained (for every individual patient), as assessed by daily plasma samples. Dose of the antibiotic in both groups will also be recorded daily.
Organ dysfunction	Delta SOFA Change in SOFA Score from enrolment to day 5.
ICU length of stay	Date of ICU admission to ICU discharge, in days.
Clinical cure	Time to resolution of signs and symptoms of infection (fever resolution and normalisation of white cell count), in days.
Microbiological cure	For bacteraemia only, time taken for the blood culture to become negative, in days.
ICU mortality	Death in ICU from any cause, from the date of ICU admission. Mortality in TDM group will be compared with SOC group. Time to event analysis will be performed for this measure.
30-day mortality	Death within 30 days from date of ICU admission. Mortality in TDM group will be compared with SOC group. Time to event analysis will be performed for this measure.
ICU-free days to day 30	30 minus duration in ICU, in days Patients who die in ICU or remain in ICU for ≥30 days will be assigned zero ICU-free days.
Duration of antibiotic therapy	Length of time, in days, that the participant is on the study antibiotics, calculated from commencement of study beta-lactam.
Safety of the intervention	Acute kidney injury defined by KDIGO criteria. Drug-induced liver injury defined by DILI criteria. Clinical or EEG diagnosis of encephalopathy or seizures.
Piperacillin dose recommendation as per TDMx	Dose recommendation per TDMx. Per cent agreement between protocol dosing algorithm and TDMx, measured using the kappa statistic.
Dose recommendation per TDMx for meropenem	Dose recommendation per TDMx. Per cent agreement between protocol dosing algorithm and TDMx, measured using the kappa statistic.

AKI, acute kidney injury; DILI, drug-induced liver injury; EEGElectroencephalogramfT>MIC, free concentration for the duration of time over the minimum inhibitory concentration; ICU, intensive care unit; KDIGO, Kidney Disease Improving Global Outcomes; SOC, standard of care; SOFAsequential organ failure assessmentSOFA, sequential organ failure assessment score; TDM, therapeutic drug monitoring; TDMx, open access dosing software program