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)