Clinical response to Gram stain-guided antibiotic therapy noninferior to that of guideline-based therapy in patients with ventilator-associated pneumonia

1. Compared to guideline-based treatment, Gram stain-guided antibiotic treatment yielded noninferior clinical responses in patients with ventilator-associated pneumonia in the intensive care unit.

2. Gram stain-guided treatment also significantly reduced the use of broad-spectrum antibiotics without detrimental effects.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Gram staining of respiratory samples in patients with ventilator-associated pneumonia (VAP) in intensive care units (ICUs) is a relatively simple and inexpensive method of potentially guiding appropriate initial antibiotic therapy. However, the current literature is conflicted between the clinical utility of Gram-staining and its accuracy in detecting causative pathogens and safely limiting the overuse of broad-spectrum antibiotics. This multicenter trial compared the clinical response to Gram stain-guided restrictive antibiotic treatment vs guideline-based broad-spectrum antibiotic treatment in patients with VAP. The main endpoint was the clinical response rate after completion of antibiotic therapy, including improvement or lack of progression of baseline radiographic findings, resolution of signs and symptoms of pneumonia, and lack of antibiotic readministration, with a noninferiority margin of 20%. Secondary endpoints included the initiation of antipseudomonal and anti-methicillin-resistant Staphylococcus aureus (MRSA) agents, 28-day mortality, ICU-free days, ventilator-free days, and adverse events. Among 206 patients with VAP in the ICU, clinical response to Gram stain-guided antibiotic therapy was noninferior to that of guideline-based antibiotic therapy and reduced the use of antipseudomonal and anti-MRSA agents without detrimental effects. A limitation of this study was that there were few patients with severe VAP or septic shock included in the trial where Gram-staining and restricting broad-spectrum antibiotic coverage may not be appropriate.

Click to read the study in JAMA Network Open

Relevant Reading: Gram stain-guided antibiotic choice: a GRACEful method to safely restrict overuse of broad-spectrum antibiotic agents

In-Depth [randomized clinical trial]: This open-label, noninferiority trial (GRACE-VAP) enrolled 206 ICU patients (median [IQR] age, 69 [54-78] years; 141 men [68.4%]) from 12 tertiary centers in Japan between April 2018 to May 2020. Inclusion criteria were age ≥15 years with a diagnosis of VAP and a modified Clinical Pulmonary Infection Score of ≥5. Patients were randomized to Gram stain-guided (N = 103) or guideline-based antibiotic therapy groups (N = 103). In total, clinical response was observed in 79 patients (76.7%) in the Gram stain-guided group and 74 patients (71.8%) in the guideline-based group (risk difference, 0.05; 95%CI, –0.07 to 0.17; P < .001 for noninferiority). Compared to the guideline-based group, the Gram stain-guided group significantly decreased the use of antipseudomonal (30.1%; 95%CI, 21.5%-39.9%; P < .001) and anti-MRSA agents (38.8%; 95%CI, 29.4%-48.9%; P < .001). The cumulative incidence of mortality within 28 days was 13.6% (N = 14) vs 17.5% (N = 18) for the Gram stain-guided and guideline-based groups respectively (P = .39). Escalation of antibiotics as per culture results was performed in 7 patients (6.8%) in the Gram stain-guided group and 1 patient (1.0%) in the guideline-based group (P = .03). No significant differences in ICU-free days, ventilator-free days, and adverse events were observed between the groups.

Image: PD

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