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

Inclusion Criteria: Adults (≥ 18 years) Hospital-acquired sepsis or septic shock diagnosed in the past 24 hours (according to sepsis 3.0 definitions) 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 90 days prior to the occurrence of sepsis Prolonged mechanical ventilation (≥ 5 days on mechanical ventilation) within 90 days 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 in the past 3 months Exposure to an antibiotic (amoxicillin-clavulanic acid, C2G, C3G, fluoroquinolones) in the previous 3 months A trip abroad within 3 months to known geographical areas at risk (in particular the Indian subcontinent, South-East Asia, the Middle East and North Africa, the Mediterranean Basin) 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 ceftazidim, piperacillin-tazobactam, cefepim, meropenem, ceftazidim-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 (with the exception of acute prostatitis) 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 therapy for the new sepsis (if sepsis acquired in the hospital outside the resuscitation> 2 doses of antibiotics) Hospitalization in a short stay hospital of more than 48 hours Limitation of life support (comfort care applied only) at the time of screening Enrolment to another interventional 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)