Combined Use of a Respiratory Broad Panel mPCR and Procalcitonin to Reduce Duration of Antibiotics Exposure in Patients With Severe Community-Acquired Pneumonia

To assess the effectiveness of a management strategy combining a broad panel respiratory mPCR and an algorithm of early antibiotic de-escalation and discontinuation based on both the mPCR results and the procalcitonin (intervention) in severe CAP, as compared to a conventional strategy (control).

A multicentre, parallel-group, open-label, randomized controlled trial. The primary assessment criterion est the number of antibiotic-free days at 28 days

Randomization is performed immediately after the inclusion.

* In the intervention arm, a broad panel respiratory mPCR is performed on a lower respiratory tract sample (bronchoalveolar lavage fluid or tracheal aspirate, otherwise sputum), collected before the 12th hour following inclusion.
* In both arms, an additional lower respiratory tract sample (bronchoalveolar lavage fluid or tracheal aspirate, otherwise sputum) is collected for biological studies and banking.
* In the intervention arm, an algorithm of early antibiotic de-escalation and discontinuation is based on the early microbiological results, including the mPCR results, and the procalcitonin value. This algorithm is applied as soon as possible (before the 24th hour following inclusion if possible).
* In the control arm, initial antibiotic therapy is maintained, according to guidelines.
* In both arms, after 72 hours of antibiotic therapy, ICU physicians are advised to use procalcitonin (values and kinetics) to guide antibiotic therapy discontinuation, with a recommended total duration of 7 days, unless otherwise indicated.
* In both arms, a switch to oral therapy is encouraged

Eligibility Criteria:
Inclusion Criteria:

* Adults (≥18 years) with CAP admitted to the ICU since 18 hours or less; the diagnosis of pneumonia includes two clinical criteria among a temperature \> 37.8°C, tachypnea (respiratory rate \> 25/min), chest pain, cough, expectoration, localized crackles, with or without signs of pleural effusion, pulse oximetry less than 92% while breathing room air, and a newly-appeared parenchymal infiltrate; the pneumonia is community-acquired if the time between hospital admission and ICU referral is below or equal to 48 hours.
* Informed consent or emergency procedure.

Exclusion Criteria:

* Pregnancy;
* Congenital immunodeficiency;
* HIV infection with the lymphocyte CD4 count below 200/mm3 or unknown in the last year;
* Acute hematologic malignancy;
* Neutropenia (\<1 leucocyte/mL or \< 0.5 neutrophil/mL);
* Immunosuppressive drugs within the previous 30 days, including anti-cancer chemotherapy and anti-rejection drugs for organ/bone marrow transplant
* Corticosteroids ≥ 20 mg/d of prednisone equivalent for more than 14 days;
* chronic obstructive pulmonary disease (COPD) with previous history of colonization/infection with Pseudomonas aeruginosa;
* Tracheostomy;
* Diffuse bronchiectasis, cystic fibrosis;
* Aspiration pneumonia;
* Moribund patient or death expected from underlying disease during the current admission;
* Patient deprived of liberty or under legal protection measure;
* Participation in another interventional trial.