Optimising TREATment for Severe Gram-Negative Bacterial Infections

Launched by NATIONAL UNIVERSITY OF SINGAPORE · May 26, 2025

Keywords

ClinConnect Summary

The TREAT-GNB clinical trial is designed to find the best antibiotic treatments for serious infections caused by multidrug-resistant Gram-negative bacteria, which can lead to bloodstream infections and pneumonia (lung infections). The goal is to see how different treatments can help improve survival rates in patients suffering from these severe infections. This trial is currently recruiting participants aged 65 and older who have specific types of infections and are suitable for at least two different antibiotic options.

If you or a loved one are eligible, you can expect to receive one of the antibiotics being tested while being closely monitored for how well it works over a 28-day period. To participate, patients must be diagnosed with certain types of infections and be receiving intravenous antibiotics. However, the study cannot include those who are in end-of-life care, pregnant women, children, or those with other specific medical conditions. This trial aims to provide hope and possibly better outcomes for patients facing tough infections that are hard to treat.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • A: Bloodstream infections
• • a) Suitable for at least 2 antibiotic regimens in the site randomisation list
• • 1. Growth of Gram-negative bacilli identified from blood culture(s)
• • 2. Receiving or planning to receive intravenous antibiotics
• • 3. Expected time from blood culture sampling to randomisation is ≤ 96 hours.
• • OR
• B: Ventilator-associated pneumonia / hospital-acquired pneumonia a) Suitable for at least 2 antibiotic regimens in the site randomisation list b) Infection syndrome definitions\^( (US Centers for Disease Control and Prevention National Healthcare Safety Network)3: i) At least one of the following:
• • 1. temperature \> 38 °C
• • 2. white blood cell count ≥ 12,000 cells/mm3 (12 x 109/L, 12 x 103/µL) or ≤ 4,000 cells/mm3 (4 x 109/L, 4 x 103/µL)
• 3. altered mental status with no other causes in \> 70 years old; AND ii) Two or more chest imaging tests demonstrating at least one of the following:
• 1) new and progressive OR progressive and persistent infiltrate 2) new and persistent OR progressive and persistent consolidation 3) new and persistent OR progressive and persistent cavitation; AND iii) At least two of the following:
• • 1. new onset of purulent sputum, or change in character of sputum, or increased respiratory secretions, or increased in suctioning requirements
• • 2. new onset or worsening tachypnoea or dyspnoea
• • 3. rales or bronchial breath sounds
• • 4. worsening gas exchange defined by oxygen desaturations (e.g., PaO2/FiO2 \< 240), increased oxygen requirements or increased ventilation demand.
• • c) Hospital admission \> 48 hours d) Predominant growth of Gram-negative bacilli identified from respiratory tract specimen(s)\*; e) Receiving or planning to receive intravenous antibiotics f) Expected time from respiratory culture sampling to randomisation is ≤ 96 hours
• • AND
• • C: CR-GNB antibiotic backbone domain
• • a) Gram-negative bacilli belonging to Acinetobacter baumannii-calcoaceticus complex, Pseudomonas aeruginosa or Enterobacterales b) Carbapenem resistance in isolate detected - i) Phenotypically via conventional microbiology testing: meropenem / imipenem / ertapenem resistance; OR ii) Genotypically via PCR or next generation sequencing: presence of genes associated with carbapenemase production (eg. blaNDM, blaKPC, blaIMP, blaIMI, blaVIM, blaOXA-48-like).
• Exclusion Criteria:
• • 1. Treating team deems enrolment in the study is not in the best interest of the patient
• • 2. Patient is on end-of-life care
• • 3. Patient is incarcerated in a correctional facility
• • 4. Participation in any interventional study activities outlined in the TREAT-GNB study within the last 90 days
• • 5. Pregnant women and children
• • OR
• • 6. Polymicrobial bloodstream infection