Use of a Respiratory Multiplex PCR and Procalcitonin to Reduce Antibiotics Exposure in Patients With Severe Confirmed COVID-19 Pneumonia

Inclusion (D0_H0) is performed in ICU as soon as possible, once the diagnosis of COVID-19 pneumonia is confirmed. Therefore, inclusion might be performed either on ICU admission (if the COVID-19 pneumonia has been confirmed in the pre-ICU wards) or during the ICU stay (if the COVID-19 pneumonia was confirmed after ICU admission). Conventional microbiological investigations are left at the discretion of the physicians, and may include blood cultures, Streptococcus pneumoniae and Legionella pneumophila urinary antigen assays, and a respiratory tract sample for Gram stain examination and 2 days-long culture (if not already done in the past 24 hours). Usual biology includes procalcitonin measurement. Empirical antimicrobial therapy combines a third-generation cephalosporin and a macrolide, or broader-spectrum antibiotics if risk factors for resistant bacteria are identified.

Randomization is performed immediately after the inclusion.

• In the intervention arm, a broad panel respiratory Mpcr FA-PPP is performed on respiratory tract sample (tracheal aspirate, BAL or sputum), collected 12 hours after inclusion. An algorithm of early antibiotic adaptation and discontinuation, based on the microbiological results, including the mPCR FA-PPP results, and the procalcitonin values and kinetics will be used. This algorithm will be applied as soon as possible after inclusion, and repeated day after day until D7.
• In the control arm, the antimicrobial therapy is left at the discretion of the physicians, as in usual practice.

Evaluation criteria are collected at hospital discharge or at D28, and D90. The vital status may be obtained by phone call at D28 (if the patient has been discharged before D28) and at D90.

Inclusion criteria

• Adults (>= 18 years) admitted to the ICU;
• Severe confirmed COVID-19 pneumonia, defined by i) a newly-appeared pulmonary parenchymal infiltrate; and ii) a positive RT-PCR (either upper or lower respiratory tract) for COVID-19 (SARS-CoV-2); iii) and admission to the ICU or intermediate care unit;
• Informed consent or emergency procedure.

Exclusion criteria

• Pregnancy ;
• Congenital immunodeficiency;
• HIV infection with CD4 count below 200/mm3 or unknown in the last year;
• High-grade hematological malignancy;
• Neutropenia (<1 leucocyte/mL or < 0.5 neutrophil/mL);
• Immunosuppressive drugs within the previous 30 days, including anti-cancer cytotoxic chemotherapy and anti-rejection drugs for organ/bone marrow transplant;
• Moribund patient or death expected from underlying disease during the current admission;
• Patient deprived of liberty or under legal protection measure