GRACE-VAP

Trial question

Is Gram stain-guided antibiotic therapy noninferior to guideline-based antibiotic therapy in patients with ventilator-associated pneumonia?

Study design

Multi-center

Open label

RCT

Population

Characteristics of study participants

32.0% female

68.0% male

N = 206

206 patients (65 female, 141 male).

Inclusion criteria: patients with ventilator-associated pneumonia in the ICU.

Key exclusion criteria: known allergy to study medications; discharge from ICU; HF; atelectasis; receipt of antibiotics for > 24 hours; withdrawal or withholding of life support; COVID-19 infection.

Interventions

N=103 Gram stain-guided antibiotic therapy (selection of antibiotics guided by Gram staining of the endotracheal aspirate).

N=103 guideline-based antibiotic therapy (combination of an anti-pseudomonal agent and anti-MRSA agent).

Primary outcome

Clinical response

76.7%

71.8%

76.7 %

57.5 %

38.4 %

19.2 %

0.0 %

Gram stain-guided antibiotic therapy

Guideline-based antibiotic therapy

Difference not exceeding non-inferiority margin ✓

Difference not exceeding non-inferiority margin in clinical response (76.7% vs. 71.8%; AD 5%, 95% CI -7 to 17).

Secondary outcomes

No significant difference in death at day 28 (13.6% vs. 17.5%; HR 0.74, 95% CI 0.37 to 1.48).

Significant decrease in the use of antipseudomonal agents (69.9% vs. 100%; ARD -30.1, 95% CI -21.5 to -39.9).

Significant decrease in the use of anti-MRSA agents (61.2% vs. 100%; AD -38.8%, 95% CI -29.4 to -48.9).

Safety outcomes

No significant differences in adverse events, ICU-free days, ventilator-free days.

Conclusion

In patients with ventilator-associated pneumonia in the ICU, Gram stain-guided antibiotic therapy was noninferior to guideline-based antibiotic therapy with respect to clinical response.

Reference

Jumpei Yoshimura, Kazuma Yamakawa, Yoshinori Ohta et al. Effect of Gram Stain-Guided Initial Antibiotic Therapy on Clinical Response in Patients With Ventilator-Associated Pneumonia: The GRACE-VAP Randomized Clinical Trial. JAMA Netw Open. 2022 Apr 1;5(4):e226136.

Open reference URL

Create free account