Pulmonary Diffusion of Antibiotics in Patients Admitted for ARDS Following SARS-CoV-2 Pneumonia

Not Applicable

Recruiting

• Conditions: SARS-CoV 2 Pneumonia; ARDS
• Interventions: Other: blood sample and bronchoalveolar lavage

• Registration Number: NCT05464680
• Lead Sponsor: Assistance Publique Hopitaux De Marseille

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-07-14
• Study First Submitted QC: 2022-07-18
• Study First Posted: 2022-07-19
• Study Start: 2022-11-24
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-18
• Last Update Posted: 2024-10-22
• Primary Completion: 2026-11-23
• Study Completion: 2027-02-23

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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.

  2. 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.

  3. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients positive to SARS-CoV 2	blood sample and bronchoalveolar lavage	Patients admitted to the ICU and placed on VM following SARS-CoV-2 pneumonia
Patients negative to SARS-CoV 2	blood sample and bronchoalveolar lavage	Patients admitted to the ICU and placed on VM outside of SARS-CoV-2 pneumonia

Primary Outcome Measures

Name	Time	Method
Compare the pulmonary diffusion of piperacillin	48 hours following antibiotics administration	Dosage in the epithelial lining fluid

Secondary Outcome Measures

Name	Time	Method
Pulmonary diffusion of tazobactam	48 hours following antibiotics administration	Dosage in the epithelial lining fluid
Concentrations of tazobactam in effective pulmonary and plasma targets	48 hours following antibiotics administration	Tazobactam concentrations in Epitehlial Lining Fluid and plasma separately at H48 and 7 days after initiation of antibiotic therapy
Concentrations of piperacillin in effective pulmonary and plasma targets	7 days following antibiotics administration	Piperacillin concentrations in plasma

Trial Locations

Locations (1)

Service Médecine Intensive Réanimation; 🇫🇷 Marseille, France