Japan: Study on Gram Stain-Guided Therapy for VAP

In patients with ventilator-associated pneumonia (VAP), gram stain-guided therapy was non-inferior to guideline-based treatment and dramatically decreased the usage of broad-spectrum antibiotics, says an article published in the Journal of American Medical Association.

Gram staining should offer quick results for identifying causal organisms. However, the influence of Gram staining on reducing the first antibiotic choice in intensive care units (ICUs) has not been studied. As a result, Jumpei Yoshimura and colleagues undertook this study to assess the clinical response of Gram stain-guided restriction guideline-based broad-spectrum antibiotic therapy vs antibiotic therapy in patients with VAP.

From April 1, 2018, to May 31, 2020, this multicenter, open-label, noninferiority randomized clinical study was undertaken in the ICUs of 12 tertiary referral institutions in Japan. Patients aged 15 and up with a VAP diagnosis and a modified Clinical Pulmonary Infection Score of 5 or above were eligible. The population for the primary analysis was based on the per-protocol analysis population. Patients were randomly assigned to either Gram stain–guided antibiotic treatment or antibiotic therapy based on guidelines. The primary endpoint was the clinical response rate; the adverse event was defined as reaching the end of antibiotic therapy within 14 days, betterment or lack of advancement of baseline radiographic findings, resolution of pneumonia signs and symptoms, and absence of antibiotic agent re-administration, with a non-inferiority margin of 20%.

Key Findings

• In all, 206 patients were randomly assigned to either the Gram stain–guided (n = 103) or the guideline-based (n = 103) groups.
• Clinical response occurred in 79 (76.7%) of the Gram stain–guided patients and 74 (71.8%) of the guideline-based patients.
• The Gram stain–guided group used fewer antipseudomonal and anti-MRSA drugs than the guideline-based group.
• The 28-day cumulative incidence of death in the Gram stain–guided group was 13.6% (n = 14) versus 17.5% (n = 18) in the guideline-based group (P =.39).
• Antibiotic escalation based on culture findings was conducted in 7 patients (6.8%) in the Gram stain–guided group and 1 patient (1.0%) in the guideline-based group.
• There were no significant differences in ICU-free days, ventilator-free days, or adverse events across the groups.

In conclusion, this study supports the use of Gram staining in critical care settings to reduce the spread of MDR bacteria.

Reference: Yoshimura J, Yamakawa K, Ohta Y, 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;5(4):e226136. doi:10.1001/jamanetworkopen.2022.6136