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

Assistance Publique - Hôpitaux de Paris411 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

411

Conditions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

The effectiveness of a management 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 in severe CAP, as compared to a conventional strategy

the number of antibiotic free days at D28, which corresponds to the number of days alive without any at Day 28.

Time frame: Day 28

Secondary Outcomes

Mortality at 28 (D28) and 90 days (D90);

Mortality rate at D28 and D90

Time frame: Day 28 and day 90

Number of defined daily dose (DDD) per 100 patient days of broad- and narrow-spectrum antibiotics

Time frame: Day 28

Antibiotics duration at D28

Time frame: Day 28

Number of organ-failure free days (based on SOFA) at D28

Time frame: Day 28

Incidence rates of bacterial superinfections at D28

Time frame: Day 28

Incidence rates of colonization/infection with multidrug resistant bacteria and Clostridium difficile infections at D28

Time frame: Day 28

Incidence rates of relapse (same pathogen) or reinfection (another pathogen) at D28

Time frame: Day 28

Duration of ICU and hospital stay

Time frame: Day 90

Cost of the total hospital admissions (including 90-day repeated admissions), ICU costs, cost of the microbiological diagnostic workup;

Time frame: Day 90

Incremental / decremental cost effectiveness ratio in cost per treatment success (90-day composite of all-cause death and infection recurrence).

Time frame: Day 90

Sensitivity, specificity, and likelihood ratios of the broad panel mPCR Film Array for the diagnosis of pneumonia, taking the conventional microbiological tests as reference

Time frame: Day 28

Euroquol questionary (EQ-5D-3L)

Time frame: Day 90

To assess the operational values of the broad panel mPCR Film Array for the diagnosis of ventilator associated pneumonia (in the intervention group only).

Sensitivity, specificity, and likelihood ratios of the broad panel mPCR Film Array for the diagnosis of ventilator associated pneumonia (in the intervention group only), taking the conventional microbiological tests as reference.

Time frame: Day 28

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes