Antimicrobial Stewardship For Ventilator Associated Pneumonia in Intensive Care

• Status: Not yet recruiting
• Trial end date: 2025-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Increasing emergence of multidrug resistant (MDR) bacteria worldwide is now considered one of the most urgent threats to global health. The association between increase of antibiotics consumption and resistance emergence has been well documented for all patients admitted to the Intensive care unit (ICU) who received antibiotic treatment and for patients treated for ventilator associated pneumonia (VAP).

Reduction of use of antibiotics is a major point in the war against antimicrobial resistance. VAP is the first cause of healthcare-associated infections in ICU and more than half of antibiotics prescriptions in ICU are due to VAP.

Once the diagnosis of pneumonia under MV has been made, initiation of antibiotic treatment must be prompt but there is no clear consensus on its duration. In the case of a good clinical response to treatment, it has been shown in some situations that short course antibiotics can be effective without side effects and antimicrobial stewardship initiatives can be applied successfully and effectively to the management of Community Acquired Pneumonia (CAP).

The hypothesis is that an antimicrobial stewardship is possible in the treatment of VAP with no increase in the rate of all-cause mortality, treatment failure or occurrence of new episode of pneumonia.

The objective is to investigate whether an antimicrobial stewardship for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would be non-inferior in terms of all-cause mortality, treatment failure or occurrence of new episode of pneumonia.

This study will be a prospective, national multicenter (24 centers), phase III, comparative randomized (1:1), single-blinded clinical trial comparing two management strategies of treatment of pneumonia on the basis of two parallel arms:

Experimental group: Antimicrobial stewardship based on daily clinical assessment of clinical cure.

Control group: standard management: duration of appropriate antibiotic therapy for confirmed VAP according to guidelines.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Anti-Bacterial Agents; Anti-Infective Agents

Criteria

Inclusion Criteria:

• Patient under MV

• Diagnosis of microbiologically confirmed of first episode of VAP

• Initial appropriate empiric antibiotic therapy

• Written informed consent from the patient or a legal representative if appropriate. If absence of a legal representative the patient may be included in emergency procedure

Definitive diagnosis of pneumonia (in agreement with international guidelines) is defined by association:

• Patient under MV>48 hours

• New pulmonary infiltrate of which an infectious origin is strongly suspected

• Worsening oxygenation

• Have the following clinical criteria within the 24 hours prior to the first dose of antibiotic therapy

• Purulent tracheal secretions

• And at least 1 of the following : documented fever (body temperature >38,3°C) or hypothermia (body temperature <35°C) or white blood cell (WBC) count >10,000 cells/mm3 or <4,000 cells/mm3

• Microbiological criteria (positive quantitative culture of a lower respiratory tract (LRT): bronchoalveolar lavage fluid (BAL) (significant threshold ≥10^4 colony-forming units/mL) or plugged telescopic catheter (PTC) (significant threshold ≥ 10^3 colony-forming units/mL) or quantitative endotracheal aspirate (ETA) distal pulmonary secretion samples (significant threshold ≥10^5 colony-forming units/mL)

Exclusion Criteria:

• Patient under selective decontamination of the digestive tract

• Concomitant extra-respiratory infection requiring antibiotic therapy at the moment of inclusion

• Inclusion in another interventional study concerning antimicrobial strategies

• Moribund (IGS II>80)

• Thoracic trauma with Abbreviated Injury Scale (AIS) thorax ≥ 3

• Severely immunocompromised patients (such as congenital immunodeficiency, neutropenia (<1leucocyte/ml or <0.5 neutrophil/ml) or acute hematologic malignancy or stem cell transplant, HIV infection with CD4 count below 200/mm3

• Patients undergoing immunosuppressive therapy and long term corticotherapy > 0.5 mg/kg

• VAP due to: Pseudomonas aeruginosa, Carbapenem-resistant Acinetobacter spp, Carbapenem-resistant Enterobacteriaceae

• Bacterial VAP in a context of COVID-19 or other confirmed viral pneumonia

• Patients with empyema, necrotizing and abscessed pneumonia

• Pregnant women

• No health insurance coverage