Individualised, short-course antibiotic treatment vs usual long-course treatment for VAP: a multicentre, individually randomised, open-label, non.....

Open AccessPublished:January 22, 2024DOI:https://doi.org/10.1016/S2213-2600(23)00418-6

Background

Ventilator-associated pneumonia (VAP) is a significant concern in intensive care units, contributing to increased mortality, prolonged hospital stays, and the overuse of antibiotics, which in turn leads to antimicrobial resistance. This phase 4 trial aimed to determine whether a pragmatic, individualised short-course antibiotic treatment for VAP is non-inferior to the usual long-course treatment.

Methods

The trial was conducted in 39 intensive care units across six hospitals in Nepal, Singapore, and Thailand. Adult patients (age ≥18 years) who met the US Centers for Disease Control and Prevention criteria for VAP, had been mechanically ventilated for at least 48 hours, and were receiving culture-directed antibiotics were included. Participants were randomly assigned to either an individualised short-course treatment (≤7 days, as short as 3-5 days) or usual care (≥8 days). The primary outcome was a 60-day composite endpoint of death or pneumonia recurrence. The non-inferiority margin was set at 12%.

Findings

From May 2018 to December 2022, 461 patients were enrolled and randomly assigned to either the short-course (232 patients) or usual care group (229 patients). The median age was 64 years, and 39% of participants were female. The intention-to-treat analysis included 460 patients after one withdrawal. The median duration of antibiotic treatment was 6 days for the short-course group and 14 days for the usual care group. The primary outcome occurred in 41% of the short-course group and 44% of the usual care group (risk difference –3% [one-sided 95% CI –∞ to 5%]). Non-inferiority was established, though superiority was not. Antibiotic side effects were significantly lower in the short-course group (8% vs 38%).

Interpretation

This study demonstrated that individualised short-course antibiotic treatment for VAP is non-inferior to longer treatment durations in terms of 60-day mortality and pneumonia recurrence, while significantly reducing antibiotic use and side effects. This approach could help mitigate the burden of side effects and the risk of antibiotic resistance, particularly in resource-limited settings.

THE LANCET: Respiratory Medicine

January 22, 2024

Individualized, short-course antibiotic treatment versus usual long-course treatment for ventilator-associated pneumonia.

Summarized by:?Dr. Mazen Kherallah

The study was a phase 4, randomized, open-label trial conducted in 39 ICUs across Nepal, Singapore, and Thailand. It used a non-inferiority–superiority framework with patients assigned 1:1 to groups using stratified permuted blocks. Blinding was partial, with assessors and participants unaware of treatment allocation, but not clinicians. The non-inferiority margin was set at 12%, and analyses included both intention-to-treat and per-protocol populations.

Population:

• Adults (age ≥18 years) with ventilator-associated pneumonia (VAP), mechanically ventilated for ≥48 hours, administered culture-directed antibiotics.
• 461 patients (232 in the short-course group, 229 in the usual care group).
• Median age 64 years; 39% female.

Intervention:

• Individualized short-course antibiotic treatment for VAP.
• DUration of antibiotics: ≤7 days, potentially as short as 3–5 days.

Comparison:

• Usual care for VAP.
• Duration of antibiotics ≥8 days, determined by primary clinicians.

Outcome:

• Primary Outcome: 60-day composite of death or pneumonia recurrence.
• Intention-to-Treat Analysis (460 patients): Short-course Group: 41% met the primary outcome; median antibiotic duration was 6 days (IQR 5–7 days). Usual Care Group: 44% met the primary outcome; median antibiotic duration was 14 days (IQR 10–21 days).
• Per-Protocol Population (435 participants): Similar results as intention-to-treat, confirming non-inferiority.
• Antibiotic Side-Effects: Significantly lower in the short-course group (8%) versus the usual care group (38%).

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Watch the following video on "Nebulized Antibiotics for Ventilator-Associated Pneumonia: What is the best song?" by ICU REACH

Discussion Questions:

1. How can the implementation of individualised short-course antibiotic treatment strategies impact the overall management of VAP in different healthcare settings?
2. What are the potential challenges and solutions for adopting short-course antibiotic regimens in intensive care units with high rates of multidrug-resistant infections?
3. How might this study influence future guidelines and clinical practices regarding the treatment duration for VAP?

Javier Amador-Casta?eda, BHS, RRT, FCCM, PNAP

Interprofessional Critical Care Network (ICCN)

[email protected]

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