Table 1.

Outcome definitions and time frames

Primary endpoint and time frame	Definition and assessment
Clinical cure Days 3–5 after treatment*	TOC, the situation where all the following conditions are met: survival at the time of the evaluation; complete resolution of all symptoms and signs of infection (or return to the situation prior to current infection); no need for prolonged antibiotic treatment beyond the recommended duration* and no need for treatment modification due to unfavourable clinical response.

Secondary endpoint and time frame	Definition and assessment
Clinical response After 5 days of treatment (early response) Until day 60 of follow-up (late response)	Same as clinical cure
Microbiological cure After 5 days of treatment (early response) Until day 60 of follow-up (late response)	Negative blood cultures and where applicable, negative cultures from samples taken from initial infection focus. ‘Presumptive microbiological cure’ is accepted in those cases where it is not possible to prove the negativisation of isolates from initial focus
All-cause mortality 7, 14 and 60 days of follow-up	Death for any reason
Length of hospital stay	Time from randomisation to hospital discharge
Clinical recurrence (relapse or reinfection) rates 60 days of follow-up	Recurrence of at least one clinical and one analytical sepsis criterion, with presence or absence of bacteraemia
Microbiological recurrence (relapse or reinfection) rates 60 days of follow-up	New BSI episode with the same isolate as initial cultures with previously clinical and microbiological cure
Number of days of antipseudomonal beta-lactam avoided Until end of treatment	Number of days of antibiotic treatment with an antipseudomonal beta-lactam avoided
Ecological impact 7–14, 12–21, 30 days	Intestinal colonisation by multidrug-resistant Gram-negative bacilli
Safety of drugs—adverse events Until day 60 of follow-up	Any untoward medical occurrence associated with the use of a drug in humans, whether considered drug related.
Composite secondary variables 7–14, 60 days of follow-up	Survival on day 14, number of days with an antipseudomonal beta-lactam avoided, presence or absence of side effects, including C. difficile infections, secondary MDRO infections and all drug-related adverse events

*7–14 days according to IDSA, except in the presence of undrained or late-draining abscesses, when up to 4 weeks are allowed.

MDRO, Multidrug resistant organisms.