Antimicrobial Stewardship For Ventilator Associated Pneumonia in Intensive Care

Phase

N/A

Condition

Pneumonia

Treatment

Standard management

Antimicrobial Stewardship

Clinical Study ID

NCT05124977

APHP200011

Ages > 18
All Genders

Study Summary

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 (31 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Diagnosis of microbiologically confirmed of first episode of VAP
Initial appropriate antibiotic therapy (whether empirical or not)
Written informed consent from the patient or a legal representative if appropriate. Ifabsence of a legal representative the patient may be included in emergency procedure Definitive diagnosis of pneumonia (in agreement with international guidelines) is definedby association:
Patient under MV>48 hours at the time of the microbiological sampling
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 ofantibiotic therapy
Purulent tracheal secretions
And at least 1 of the following : documented fever (body temperature >38,3°C) orhypothermia (body temperature <35°C) or white blood cell (WBC) count >10,000cells/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-formingunits/mL) or plugged telescopic catheter (PTC) (significant threshold ≥ 10^3colony-forming units/mL) or quantitative endotracheal aspirate (ETA) distal pulmonarysecretion samples (significant threshold ≥10^5 colony-forming units/mL)

Exclusion

Exclusion Criteria:

Patient under selective decontamination of the digestive tract
Duration of antibiotic therapy prior to inclusion > 72h (for any reason) appropriateto the germs found in the bacterial documentation of the first episode of VAP
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 celltransplant, 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
VAP occurring in the context of co-infection of COVID-19 or other viral pneumonia (confirmed by RT-PCR)
Patients with empyema, necrotizing and abscessed pneumonia
Patients requiring extracorporeal oxygen therapy (ECMO), either veno-venous orveno-arterial
Pregnant women
No health insurance coverage

Study Design

Standard management

September 20, 2022

March 31, 2026

Study Description

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 treatment1 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. Current international guidelines define VAP as a pneumonia occurring>48 hours after endotracheal intubation and distinguishes early onset VAP occurring in the first five days after admission and late VAP, occurring after.

American guidelines strongly recommend a 7-day course of antibiotic therapy rather than a longer duration but remark that "there exist situations in which a shorter or longer duration of antibiotics may be indicated, depending upon the rate of improvement of clinical, radiologic, and laboratory parameters".