Rhode Island Hospital’s test to detect pneumonias caused by Staphylococcus aureus, Pseudomonas aeruginosa, and Haemophilus influenzae aims to be done on whole blood drawn directly from the patient, making it less invasive than other methods that obtain samples from the airways, such as bronchoscopy or deep suctioning. A simple, needle-stick blood collection from the arm would significantly expand access and simplify current testing methods for lower-respiratory-tract infections (LRTIs), allowing testing to take place at primary care centers globally versus tertiary care settings.
The test will not require the specimen to be cultured, allowing for faster results – within four hours – as compared to traditional microbiological methods. Targeting RNA also ensures that the infection is current since RNA is less stable than DNA, lasting minutes to hours when from a bacterium. The method, however, immediately stabilizes the RNA for testing. RNA also identifies bacteria that are actively making resistance proteins, rather than bacteria with the potential for resistance based only on genomic DNA.
Innovative approach
“This innovative diagnostic approach holds the potential to improve access to testing for lower-respiratory-tract infections, including pneumonia, enabling clinicians to make faster, more informed decisions and reduce the use of broad-spectrum antibiotics,” said Erin Duffy, PhD, Chief of R&D and CARB-X. “By supporting Rhode Island Hospital’s work, CARB-X is learning whether alternative sample types in detecting LRTIs is promising for future product development.”
Pneumonia is a common clinical diagnosis that often lacks a microbiological diagnosis because the sample type is difficult to obtain and, oftentimes, no pathogen is identified. Without a microbiological diagnosis, antibiotics targeting a broad range of pathogens are used, increasing the risks for resistance along with poor outcomes if inappropriate antibiotics are chosen.
“The support from CARB-X to focus on developing a direct from blood diagnostic for lower-respiratory-tract infections expands our current NIH supported work creating a direct from blood, culture independent, diagnostic for pathogens causing sepsis targeting RNA from the bacteria using RNA sequencing data form patients,” said Sean Monaghan, MD, surgeon at Rhode Island Hospital.
Leading infectious causes of illness
Pneumonia and LRTIs are leading causes of illness and death worldwide, particularly among vulnerable populations such as the elderly, young children, and those with compromised immune systems. Pneumonia is the leading infectious cause of death in children under five, claiming the lives of over 700,000 children each year globally. In adults, LRTIs account for 2.5 million deaths annually, millions of hospitalizations and significant healthcare costs. Contributing to the rise of antibiotic resistance, broad-spectrum antibiotics are often prescribed without a clear diagnosis. The lack of rapid, accurate diagnostics exacerbates this issue, making it difficult to tailor treatments effectively and leading to overuse of antibiotics.
In March 2024, CARB-X launched a new funding solicitation to fill major R&D gaps in the global antibiotic development pipeline. More than 300 Expressions of Interest were accepted in four distinct product themes: therapeutics for infections caused by Gram-negative pathogens, prevention of invasive disease, diagnostics for neonatal sepsis, proof-of-concept for novel sample types for diagnosing LRTIs. Additional projects are under review, and new product developers will be announced this year.
When CARB-X was founded in 2016, the early-stage antibiotic pipeline was stalled. Since its inception, CARB-X has supported 110 R&D projects in 13 countries, and CARB-X product developers have made significant progress: 18 projects have advanced into or completed clinical trials; 12 remain active in clinical development, including late-stage clinical trials; and two diagnostic products have reached the market. Additionally, at least 9 product developers with active R&D projects have already secured advanced development partnerships to support their clinical development after leaving the CARB-X portfolio. All CARB-X funded product developers are contractually obligated to develop a Stewardship and Access Plan for their funded product, outlining strategies to ensure responsible stewardship and appropriate access in low- and middle-income countries.
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