Pneumonia are the most frequent infectious complication in patients on Extracorporeal Membrane Oxygenation Veno-arterial (ECMO-VA), with a treatment failure rate of around 40%, even though antibiotic therapy is tailored to the germs identified. One hypothesis to explain this particularly high failure rate is the reduced pulmonary blood flow associated with ECMO offloading of the heart. Although there are no data to date on the pulmonary penetration of antibiotics in patients undergoing VA-ECMO, this phenomenon of pulmonary hypoperfusion could contribute to altering the alveolocapillary diffusion of antibiotics, thereby reducing their concentration in the pulmonary parenchyma. Our hypothesis is that amikacin nebulization could increase bacterial clearance and, ultimately, limit treatment failure or recurrence of gram-negative bacilli (GNB) pneumonia in patients undergoing VA-ECMO.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
26
Patients included in the inhaled amikacin group will receive inhaled antibiotic therapy by nebulization of amikacin at a dose of 25 mg/kg in 1 daily dose (+/- 3 hours apart), within 6 hours of randomization and for a total duration of 5 days.
Patients included in the standard of care group will not receive any nebulization. They will receive Standard care alone.
Bacterial eradication rate
Bacterial eradication rate, defined as absence of germs on direct examination and negative culture of a tracheal aspirate taken on day 5 (D5) after randomization and at least 12 hours after the last administration of inhaled amikacin.
Time frame: Day 5
Clinical cure rate
Clinical cure rate, defined as disappearance of clinical signs suggestive of pneumonia, biological inflammatory syndrome and correction of haematosis disorders, at D5.
Time frame: Day 5
Pneumonia persistence rate
Pneumonia persistence rate defined as the presence of the pathogen identified at a significant level on culture of tracheal aspirate at D5.
Time frame: Day 5
Change in clinical pulmonary infection score (CPIS)
Difference between CPIS score at D5 and CPIS score at randomization.
Time frame: Day 0 to Day 5
Change in pulmonary aeration score
Difference between ultrasound pulmonary aeration score at D5 and pulmonary aeration score at randomization.
Time frame: Day 0 to Day 5
Adverse events
Quantifying and analysing adverse events and serious adverse events
Time frame: Day 0 to Day 5
Pharmacokinetic analysis of piperacillin tazobactam
Pharmacokinetic analysis of plasma concentrations of the piperacillin - tazobactam combination
Time frame: Day 1
Alveolar fluid penetration ratio of piperacillin-tazobactam
Measurement of the alveolar fluid penetration ratio (AUC\* alveolar fluid / AUC plasma) of piperacillin-tazobactam in patients on ECMO-VA after 2 days of intravenous antibiotic administration. \*Area Under the Curve
Time frame: Day 1
Pharmacokinetic analysis of Amikacin
Measurement of the plasma concentration of Amikacin in patients on ECMO-VA in the treatment group between D1 and D5.
Time frame: Day 1 to Day 5
Alveolar fluid concentration of Amikacin
Measurement of the alveolar fluid concentration of Amikacin in patients on ECMO-VA after one nebulization in the treatment group (after 24 hours of treatment)
Time frame: Day 1
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