Prevention of early ventilation-acquired pneumonia (VAP) in comatose brain-injured patients by a single dose of ceftriaxone: PROPHY-VAP study protocol, a multicentre, randomised, double-blind, placebo-controlled trial

Abstract

IntroductionVentilator-associated pneumonia (VAP) is the first cause of healthcare-associated infections in intensive care units (ICUs) and brain injury is one of the main risk factors for early-onset VAP. Antibiotic prophylaxis has been reported to decrease their occurrence in brain-injured patients, but a lack of controlled randomised trials and the risk of induction of bacterial resistance explain the low level of recommendations. The goal of this study is to determine whether a single dose of ceftriaxone within the 12 hours postintubation after severe brain injury can decrease the risk of early-onset VAP.Methods and analysisThe PROPHY-VAP is a French multicentre, randomised, double-blind, placebo-controlled, clinical trial. Adult brain-injured patients (n=320) with a Glasgow Coma Scale ≤12, requiring mechanical ventilation for more than 48 hours, are randomised to receive either a single dose of ceftriaxone 2 g or a placebo within the 12 hours after tracheal intubation. The primary endpoint is the proportion of patients developing VAP from the 2nd to the 7th day after mechanical ventilation. Secondary endpoints include the proportion of patients developing late VAP (>7 days after tracheal intubation), the number of ventilator-free days, VAP-free days and antibiotic-free days, length of stay in the ICU, proportion of patients with ventilator-associated events and mortality during their ICU stay.Ethics and disseminationThe initial research project was approved by the Institutional Review Board of OUEST III (France) on 20 October 2014 (registration No 2014-001668-36) and carried out according to the principles of the Declaration of Helsinki and the Clinical Trials Directive 2001/20/EC of the European Parliament relating to the Good Clinical Practice guidelines. The results of this study will be presented in national and international meetings and published in an international peer-reviewed journal.Trial registration numberNCT02265406; Pre-results.

Risk Factors of Ventilator-Associated Pneumonia in Critically III Patients

“…For burn patients, fluid infusion should be limited to reduce infection (Luo and Guo, 2015). Although studies have shown that long-term prophylactic use of antibiotics can lead to changes in pathogen resistance, other studies have confirmed that early (<7 days) empirical use of antibiotics in ICU can reduce the incidence of VAP (Dahyot-Fizelier et al, 2018; Evans et al, 2018). A study has shown that β-lactam antibiotics, such as piperacillin-tazobactam, can reduce the incidence of early VAP, but have little effect on the incidence of late VAP (Mirtalaei et al, 2019).…”

Antibiotic prophylaxis in the ICU: to be or not to be administered for patients undergoing procedures?

“…However, this finding is inconsistent and if it does exist, the strength of this effect remains to be determined. At this time, the results of a trial planned to include 320 patients with brain injury randomised to either one dose of ceftriaxone within 12 h of intubation or placebo are expected [27]. Additional multicentre prospective studies are required.…”

Analysis of risk factors for early-onset ventilator-associated pneumonia in a neurosurgical intensive care unit

“…Ventilator-associated pneumonia (VAP) remains a common complication among neurosurgery intensive care unit (NICU) patients who require invasive mechanical ventilation. Several measures are available to decrease the incidence of VAP, and these include elevation of the head of the bed, maintenance of tracheal cuff pressure, spontaneous awakening trials and starting enteral nutrition as early as possible [ 1 , 2 ]. However, despite the application of these interventions, VAP is reported to affect 5–40% of patients receiving mechanical ventilation for more than 2 days[ 3 , 4 ].…”