Trial on a Strategy Combining Rapid Diagnostic Testing and Antimicrobial Stewardship to Improve Antibiotic Use in Patients With Hospital-acquired Pneumonia.
Trial on a Strategy Combining Rapid Diagnostic Testing and Antimicrobial Stewardship to Improve Antibiotic Use in Patients With Hospital-acquired Pneumonia.
Hospital-Acquired Pneumonia (HAP) is the second most frequent hospital-acquired infection in
 the US and Europe and accounts for a large proportion of antibiotics prescribed in hospitals.
 Conventional methods to identify causative microorganisms (virus, bacteria) are
 time-consuming and sometimes inaccurate, leading to inadequate treatment in a large
 proportion of HAP patients.

 The FILMARRAY® Pneumonia Panel (FA-PP, bioMérieux) is an automated diagnostic device,
 allowing detection of multiple pathogens and resistance markers in one hour. Strategies
 combining rapid diagnostic testing and intervention of specialists in infectious diseases
 (i.e. antimicrobial stewardship -AMS - experts) showed significant synergistic impact on
 antibiotic use, mortality and costs in bloodstream infections.

 The trial hypothesis is that a strategy combining antimicrobial stewardship and FA-PP
 improves quality of care in HAP patients, as compared to antimicrobial stewardship alone.

 The trial will include patients hospitalized for ≥ 48 hours, aged 18 years or older, who have
 criteria of pneumonia: new lung infiltrate on a chest-x ray, plus evidence that the
 infiltrate is of an infectious origin (i.e. new onset of fever and/or purulent sputum and/or
 leukocytosis and/or decline in oxygenation).

 After informed consent, participants will be randomly allocated to either the intervention or
 the control arm.

 In the control arm, management of HAP patients will include clinical examination and
 conventional microbiological tests. Antibiotic choice will be discussed between AMS experts
 and the physician in charge of the patient.

 In the intervention arm, in addition to the procedures above, the strategy will include rapid
 testing using the FA-PP on a respiratory specimen, obtained by either invasive or
 non-invasive sampling. No additional invasive procedures will be required for the study, and
 FA-PP will be performed on samples collected as part as routine care.

 Investigators will visit the patient at inclusion, on day 3 and on day 30 (or at hospital
 discharge) to collect data on comorbidities, clinical outcomes, results of microbiological
 tests and antibiotics. At the end of follow-up, we will compare the number of days on
 broad-spectrum antibiotics, the incidence of negative outcomes, the length of stay and costs
 in the two arms.

 The use of the FA-PP is expected to prompt early adjustment of antibiotic therapy, improve
 outcomes, decrease length of stay, and to reduce the use of broad-spectrum antibiotics. The
 antibiotic saving may reduce the selection pressure, incidence of colonization with
 multidrug-resistant bacteria and incidence of hospital-acquired superinfections, both at an
 individual and hospital level. Moreover, this trial relies on the intervention of
 multidisciplinary AMS teams that are currently being implemented in many health facilities.
 Their transversal position offers opportunities for recruitment of patients from a wide range
 of medical and surgical departments. This project evaluates the feasibility of clinical
 trials based on the intervention of these teams, and will provide a high level of evidence
 regarding their impact on the prognosis of patients, appropriate use of antibiotics, and
 antimicrobial resistance.
Inclusion Criteria:

 -  Any patient hospitalized for ≥ 48 hours

 -  aged 18 years or older

 -  not mechanically-ventilated at inclusion

 -  with criteria of pneumonia

 -  Dated and signed inform consent

 -  Affiliation with a social security scheme

 Criteria of pneumonia:

 -  New lung infiltrate on a chest-x ray plus

 -  Evidence that the infiltrate is of an infectious origin, i.e. new onset of fever (>
 38.5°C) and/or purulent sputum and/or leukocytosis and/or decline in oxygenation

 Exclusion Criteria:

 -  • Congenital or acquired immunodeficiency: neutropenia (<1 leucocyte/mL or < 0.5
 neutrophil/mL), HIV infection, allograft/autograft of hematopoietic stem cells, solid
 organ transplantation, uptake of immunosuppressive drugs, uptake of corticosteroids
 >10 mg/day equivalent prednisone for a duration ≥15 days before screening

 -  Patients with chronic bronchitis structural changes: very severe COPD (Global
 initiative for chronic Obstructive Lung Disease GOLD 4), tracheostomy,
 bronchiectasis, cystic fibrosis

 -  Radiological evidence of thoracic empyema, pulmonary abcess

 -  Moribund patient or death expected from underlying disease during the current
 admission