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GRam stain-guided Antibiotics ChoicE for Ventilator-Associated Pneumonia (GRACE-VAP) trial: rationale and study
Jumpei Yoshimura1, Kazuma Yamakawa2, Takahiro Kinoshita1
1Division of Trauma and Surgical Critical Care, Osaka General Medical Center, 3-1-56 Bandai-Higashi, Sumiyoshi, Osaka, 558-8558, Japan.
Background:
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). 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/Design:
The 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.
Discussion:
The 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 Registration:
Clinicaltrials.gov, NCT03506113 . Registered on 29 March 2018. University Hospital Medical Information Network, UMIN000031933. Registered on 26 March 2018.
Insights
The GRACE-VAP trial investigates if Gram staining can guide antibiotic choice for ventilator-associated pneumonia (VAP), aiming to reduce broad-spectrum antibiotic use without harming patient outcomes. This study could inform antibiotic strategies in intensive care units (ICUs).
Area of Science:
- Infectious Diseases
- Critical Care Medicine
- Clinical Microbiology
Background:
- Optimizing antibiotic use is crucial to combat multidrug-resistant pathogens in intensive care units (ICUs).
- Gram staining offers rapid information for pathogen identification but its role in guiding initial antibiotic treatment for ventilator-associated pneumonia (VAP) is not well-established.
- Ventilator-associated pneumonia (VAP) is a common hospital-acquired infection in ICUs, necessitating effective treatment strategies.
Purpose of the Study:
- To assess if Gram staining can safely restrict the use of broad-spectrum antibiotics in VAP patients.
- To compare the efficacy of Gram stain-guided initial antibiotic treatment versus guidelines-based treatment.
- To provide evidence for optimizing antibiotic selection strategies in VAP.
Main Methods:
- A multicentre, randomised, open-label, parallel-group trial (GRACE-VAP) was conducted.
- Patients with VAP were randomly assigned (1:1) to either Gram stain-guided or guidelines-based initial antibiotic treatment.
- The primary endpoint was the clinical response rate; secondary endpoints included mortality, ICU/ventilator-free days, and adverse events.
Main Results:
- The study aimed to determine non-inferiority of Gram stain-guided treatment compared to guidelines-based treatment.
- Secondary analyses focused on antibiotic coverage, selection of specific agents (anti-pseudomonal, anti-MRSA), mortality, and patient recovery metrics.
- A sample size of 200 patients was estimated to provide 80% power for detecting a 20% non-inferiority margin.
Conclusions:
- The GRACE-VAP trial is expected to determine if Gram staining can reduce broad-spectrum antibiotic use in VAP.
- The study will ascertain if this approach impacts patient outcomes negatively.
- Findings will inform evidence-based antibiotic selection strategies for VAP management in ICUs.
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