Table 2 Secondary objectives and outcomes

1

To compare 14-day all-cause mortality of each regimen

Difference in proportion of those dead in each group

Day 14

2

To compare clinical and microbiologic success of each regimen at day 5

Difference in proportion of those achieving clinical and microbiological success in each group; defined as:

1. Participant alive

2. Fever resolved (< 38 °C)

3. SOFA score (ICU) or modified SOFA score (non-ICU) improved 4. Absence of growth of index organism

1. Day 5

2. Day 5

3. Day 1 and day 5

4. Up to and including day 5

3

To compare the functional outcome of patients treated with each regimen

Difference in mean change between baseline and 30-day post-randomisation FBS between groups

NB. Baseline reflects pre-admission status prior to condition meriting hospital admission.

Screening and day 30

4

To compare the rates of relapse of bloodstream infection (microbiological failure) with each regimen

Difference in proportion who experience growth of the same organism as index blood culture between groups

Up to Day 30

5

To compare the rates of new bloodstream infection with each regimen

Difference in the proportion who experience growth of a new organism from blood cultures (not a contaminant) between groups

Up to Day 30

6

To compare lengths of inparticipant hospital (acute) and ICU stay with each regimen [not including inparticipant rehabilitation, long term acute or Hospital in the Home (HITH)]

Difference in median ICU ± non-ICU length of hospital stay between groups

Cumulative up to day 30

7

To compare the number of treatment-emergent serious adverse events with each regimen

Difference in proportion of treatment-emergent serious adverse events between groups

Day 1 to the last dose plus 24 h

8

To compare rates of CDI with each regimen

Difference in proportion of clinician diagnosed (including a positive CDI test) and treated CDI between groups

30 days

9

To compare rates of colonisation and/or infection with multi-resistant bacterial organisms (MROs) including those newly acquired

Difference in proportion of those with MROs identified between groups; defined as:

1. Known previous or current colonisation and/or infection with MRO.

2. MROs detected from any clinical specimen.

MROs include vancomycin-resistant Enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA) and multi-resistant gram negative organisms including carbapenem-resistant Enterobacterales (CRE), carbapenemase-producing Enterobacterales (CPE), carbapenem-resistant Pseudomonas aeruginosa (CRP), carbapenem-resistant Acinetobacter baumannii (CRAB)

Baseline and up to day 30

10

To compare the Desirability of Outcome Ranking (DOOR) with partial credit with each regimen

Mean difference in DOOR between groups at Day 30 post-randomisation. This is based on:

1.Vital status (alive or dead)

2. C. difficile infection

3. CRE colonisation

4. Functional status (i.e. FBS)

Day 30