Abstract
BackgroundOptimising the use of antibiotic agents is a pressing challenge to overcoming the rapid emergence and spread of multidrug-resistant pathogens in intensive care units (ICUs). Although Gram staining may possibly provide immediate information for predicting pathogenic bacteria, Gram stain-guided initial antibiotic treatment is not well established in the ICU setting. We planned the GRam stain-guided Antibiotics ChoicE for Ventilator-Associated Pneumonia (GRACE-VAP) trial to investigate whether Gram staining can safely restrict the use of broad-spectrum antibiotics in patients with ventilator-associated pneumonia (VAP), which is one of the most common hospital-acquired infections in ICUs.Methods/designThe GRACE-VAP trial is a multicentre, randomised, open-label parallel-group trial to assess the non-inferiority of Gram stain-guided initial antibiotic treatment to guidelines-based initial antibiotic treatment for the primary endpoint of clinical response rate in patients with VAP. Secondary endpoints include the coverage rates of initial antibiotic therapies, the selected rates of anti-pseudomonal agents and anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) agents as initial antibiotic therapies, 28-day all-cause mortality, ICU-free days, ventilator-free days and adverse events. Patients are randomly assigned to receive Gram stain-guided treatment or guidelines-based treatment at a ratio of 1:1. In the Gram stain group, results of Gram staining of endotracheal aspirate are used to guide the selection of antibiotics. In the guidelines group, the combination of an anti-pseudomonal agent and an anti-MRSA agent is administered. A total sample size of 200 was estimated to provide a power of 80% with a one-sided alpha level of 2.5% and a non-inferiority margin of 20%, considering 10% non-evaluable patients.DiscussionThe GRACE-VAP trial is expected to reveal whether Gram staining can reduce the use of broad-spectrum antibiotics without impairing patient outcomes and thereby provide evidence for an antibiotic selection strategy in patients with VAP.Trial registrationClinicaltrials.gov, NCT03506113. Registered on 29 March 2018.University Hospital Medical Information Network, UMIN000031933. Registered on 26 March 2018.
Highlights
Optimising the use of antibiotic agents is a pressing challenge to overcoming the rapid emergence and spread of multidrug-resistant pathogens in intensive care units (ICUs)
The GRACE-ventilator-associated pneumonia (VAP) trial is expected to reveal whether Gram staining can reduce the use of broadspectrum antibiotics without impairing patient outcomes and thereby provide evidence for an antibiotic selection strategy in patients with VAP
The GRACE-VAP trial will assess whether initial Gram stain-based restriction of antibiotic therapy is non-inferior to guidelines-based initial broad-spectrum antibiotic therapy in patients with VAP in terms of the clinical response rate
Summary
The GRACE-VAP trial will assess whether initial Gram stain-based restriction of antibiotic therapy is non-inferior to guidelines-based initial broad-spectrum antibiotic therapy in patients with VAP in terms of the clinical response rate. If non-inferiority is achieved, the Gram stain-guided antibiotic choice will be considered to have several advantages in clinical settings. Gram staining can be a point-of-care test for selecting antibiotic agents because it should be easy to access at the bedside clinically. It is an inexpensive examination and easy to install in ICUs all over the world, including developing countries. Institution Division of Trauma and Surgical Critical Care, Osaka General Medical Center. Osaka General Medical Center provides central trial management and coordination
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