Beta-lactam Intermittent Versus Continuous Infusion and Combination Antibiotic Therapy in Sepsis

Inclusion Criteria: * Adults (≥ 18 years) * Hospital-acquired sepsis (according to sepsis 3.0 definitions) : * Patient hospitalized for more than 48 hours OR Patient discharged less than 48 hours ago * AND sepsis diagnosed within the last 24 hours * One of the following risk factors for gram negative multidrug resistant pathogens: * Prior intravenous antibiotic use within 7 days prior to sepsis onset with the exception of antibiotic effective only against Gram-positive bacteria, penicillin A and macrolides * Prolonged hospital stay (≥ 15 days of hospitalization) within 3 months prior to sepsis onset Prolonged mechanical ventilation (≥ 5 days on mechanical ventilation) within 3 months prior to sepsis onset * Patients with indwelling devices (dialysis access lines, intravascular lines, urinary catheter, endotracheal or tracheostomy tube, gastrostomy or jejunostomy feeding tube) * Patients known to be infected, colonized or carriers of MDR gram negative bacteria within 3 months prior to sepsis onset * Exposure to an antibiotic (amoxicillin-clavulanic acid, C2G, C3G, fluoroquinolones) within 3 months prior to sepsis onset * A trip abroad to known geographical areas at risk (in particular the Indian subcontinent, South-East Asia, the Middle East and North Africa, the Mediterranean Basin) within 3 months prior to sepsis onset * A functional or organic abnormality of the urinary tract in case of urinary tract infection. * Appropriate bacteriological sampling performed before starting antimicrobial therapy * Expected stay in ICU of more than 3 days Exclusion Criteria: * A priori known resistance to all the proposed beta-lactams or to amikacin * Need for extrarenal treatment at inclusion according to the criteria of Gaudry et al. * Known hypersensitivity to ceftazidime, piperacillin-tazobactam, cefepime, meropenem, ceftazidime-avibactam, ceftazolane-avibactam or to any of the excipients included in the corresponding pharmaceutical drugs, * Known hypersensitivity to any cephalosporin antibacterial agent, * Know hypersentitivity to any penem antibacterial agent, * Severe known hypersensitivity (eg, anaphylactic reaction, severe skin reaction) to any other beta-lactam antibiotic (eg, penicillins or monobactam ) or to any of its excipients. * Known contraindication to the aminoglycoside family including * Hypersensitivity to the active substance, to any aminoglycoside antibacterial agent or to any of the excipients included in the corresponding pharmaceutical drugs, * Cirrhosis of grades B and C according to the Child-Pugh classification. * Myasthenia gravis. * Simultaneous administration of another aminoglycoside * Association with ataluren * Non-complicated urinary tract infection (corresponding to a positive ECBU not responsible for sepsis) * Bone marrow transplant or chemotherapy-induced neutropenia * Infections for which long-term antibiotic treatment \> 8 days is strongly recommended (i.e., infective endocarditis, osteoarticular infections, anterior mediastinitis after cardiac surgery, hepatic or cerebral abscesses, chronic prostatitis for instance * Presence of antibiotic therapyfor the new sepsis before randomisation: (\> 2 doses of antibiotics or \> 16h for continuous infusion * Limitation of life support (comfort care applied only) at the time of screening * Enrolment to another interventional drug study * Pregnancy or breastfeeding * Subject deprived of freedom, subject under a legal protective measure * Non affiliation to any health insurance system * Refusal to participate to the study (patient or legal representative or family member or close relative if present)