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

Patients hospitalized in ICU with sepsis (infection with life-threatening organ dysfunction according to sepsis 3.0 definitions) presumably due to MDR-GNB (multidrug resistant Gram-negative bacteria). The study will be a prospective multicentre, randomized, open-label comparative continuous vs. intermittent pivotal βL (Beta Lactamine) antibiotic infusion strategies and combination vs. monotherapy trial conducted with a 2X2 factorial design.

Inclusion Criteria:Adults (≥ 18 years)Hospital-acquired sepsis diagnosed in the past 24 hours (according to sepsis 3.0 definitions)One of the following risk factors for 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 macrolidesProlonged hospital stay (≥ 15 days of hospitalization) within 90 days prior to the occurrence of sepsisProlonged mechanical ventilation (≥ 5 days on mechanical ventilation) within 90 days prior to sepsis onsetPatients 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 monthsAppropriate bacteriological sampling performed before starting antimicrobial therapyExpected stay in ICU of more than 3 daysExclusion Criteria:Knowledge of the germ of inclusion infection resistant to all the proposed beta-lactams or resistant to amikacinNeed for extrarenal treatment at inclusion according to the criteria of Gaudry et al.Known allergy to amikacinKnown allergy to βLNon-complicated urinary tract infection (with the exception of acute prostatitis)Bone marrow transplant or chemotherapy-induced neutropenia