Empirical Meropenem Versus Piperacillin/Tazobactam for Adult Patients With Sepsis

Inclusion Criteria: * Age ≥ 18 years * Sepsis (including septic shock) defined according to the Sepsis-3 criteria (1), i.e., suspected or documented infection and an acute increase of ≥ 2 points in the Sequential Organ Failure Assessment (SOFA) score (a marker of acute organ dysfunction) * Critical illness defined as use of at least one of the following: 1. Invasive mechanical ventilation 2. Non-invasive ventilation 3. Continuous use of continuous positive airway pressure (CPAP) for hypoxia 4. Oxygen supplementation with an oxygen flow of ≥ 10 litres (L)/minute independent of delivery system and total flows 5. Continuous infusion of any vasopressor or inotrope (excluding strictly procedure-related infusions) * Clinical indication for empirical treatment with either meropenem or piperacillin/tazobactam Exclusion Criteria: * Preceding intravenous treatment with meropenem or piperacillin/tazobactam for \> 24 hours prior to screening * Fertile women \< 60 years of age with known pregnancy or positive urine human gonadotropin (hCG) or plasma hCG * Known hypersensitivity or allergy to beta-lactam antibiotics * Suspected or documented central nervous system infection * Known infection/colonialization with microorganism with acquired resistance against meropenem or piperacillin/tazobactam within the previous 3 months (e.g., ESBL-, AmpC- or carbapenemase-producing bacteria) * Current or planned use of valproate within 30 days from randomisation * Patient included in another interventional trial where co-enrolment with EMPRESS is not permitted * Previously randomised into the EMPRESS trial * Informed consent following inclusion expected to be unobtainable * Patient under coercive measures