Clinical trial NCT05464680: Pulmonary Diffusion of Antibiotics in Patients Admitted for ARDS Following SARS-CoV-2 Pneumonia
Official title: Pulmonary Diffusion of Antibiotics During Mechanically Ventilated Pneumonia in Patients Admitted for ARDS Following SARS-CoV-2 Pneumonia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: ARDS
SARS-CoV 2 Pneumonia
Keywords: mechanical ventilation
antibiotics diffusion
ARDS
SARS-CoV 2
Lead sponsor: Assistance Publique Hopitaux De Marseille
Sponsor class: OTHER
First posted: 2022-07-19
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Patients on mechanical ventilation (MV) following SARS-CoV-2 pneumonia frequently develop ventilator-associated pneumonia (VAP). The incidence of MVAP during SARS-CoV-2 infections ranges from 50 to nearly 90%. In addition, up to 80% of recurrences of VAP (a new episode, most often attributable to the same bacteria) have been described, reflecting the failure of the initial antibiotic therapy. This incidence is much higher than that described for other etiologies of acute respiratory distress syndrome (ARDS). The investigators hypothesize that during VAP, there is an alteration of the diffusion of intravenous antibiotics in the lung parenchyma in COVID-19 patients in relation to several factors characteristic of SARS-CoV-2 infection. This altered diffusion may explain the high number of recurrences of MVAP compared to non-COVID-19 patients.


Eligibility criteria: Inclusion Criteria:

* 1. Patient over 18 years of age 2. Patient has given consent or consent obtained from the trusted person if the patient is not capable of consenting, after informed consent.

  3. Patient with ARDS 4. Patient requiring MV for ARDS (as defined by Berlin (15)), regardless of etiology (COVID-19 or other cause of ARDS) 5. Patient with suspected 1st episode of ARDS for which microbiological sampling is performed (bronchial aspiration, protected distal sampling (PDS), bronchoalveolar lavage (BAL)) 6. Patients who have received probabilistic antibiotic therapy within 24 hours of the microbiological sample, including piperacillin-tazobactam (PIP-TAZ) administered according to current recommendations.

  7. Patient who is a beneficiary of or affiliated to a social security system

Exclusion Criteria:

1. Patients for whom PIP-TAZ is administered as a discontinuous infusion.
2. Contraindication to the realization of a mini-LBA: patient whose respiratory state is too precarious for the realization of a mini-LBA for intra pulmonary antibiotics dosage (SpO2\<94% under FiO2 100% under VM), presence of a non drained pneumothorax, bronchial prosthesis, recent bronchial suture
3. Patient with a second episode of PAVM.
4. Patients with KDIGO stage ≥ 3 renal failure or extra-renal replacement therapy (creatinine measurement on the day of inclusion, performed as part of routine care).
5. Patient on ExtraCorporeal Membrane Oxygenation (ECMO) or ExtraCorporeal CO2 Removal (ECCO2R).
6. Pregnant or breastfeeding women, patients under guardianship or trusteeship, deprived of liberty
7. Patients who are moribund or for whom limitations of active therapies have been decided.
8. Any condition, which in the opinion of the investigator, would not allow the implementation of the study procedures.

Primary outcomes:
measure: Compare the pulmonary diffusion of piperacillin
timeFrame: 48 hours following antibiotics administration
Secondary outcomes:
measure: Pulmonary diffusion of tazobactam
timeFrame: 48 hours following antibiotics administration
measure: Concentrations of piperacillin in effective pulmonary and plasma targets
timeFrame: 48 hours following antibiotics administration
measure: Concentrations of piperacillin in effective pulmonary and plasma targets
timeFrame: 7 days following antibiotics administration
measure: Concentrations of tazobactam in effective pulmonary and plasma targets
timeFrame: 7 days following antibiotics administration
measure: Concentrations of tazobactam in effective pulmonary and plasma targets
timeFrame: 48 hours following antibiotics administration
Other outcomes:
Locations:
city: Marseille
country: France
facility: Service Médecine Intensive Réanimation
Study officials:
affiliation: AP-HM
name: François Cremieux
role: STUDY_DIRECTOR
References: