RNA sequencing directly from whole blood aims to expand access to LRTI testing
(BOSTON: January 28, 2025) – Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) will award Rhode Island Hospital at Brown University Health US$1M to demonstrate proof-of-concept of a polymerase chain reaction (PCR) approach informed by RNA sequencing to detect bacterial pneumonia directly from whole blood.
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.
“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.
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. Register for the CARB-X newsletter to learn about upcoming funding calls that will be announced in 2024.
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.
CARB-X is funded in part with federal funds from the U.S. Department of Health and Human Services (HHS); Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA) under agreement number 75A50122C00028 and by awards from Wellcome (WT224842), Germany’s Federal Ministry of Education and Research (BMBF), the UK Department of Health and Social Care’s Global Antimicrobial Resistance Innovation Fund (GAMRIF), the Public Health Agency of Canada (PHAC), the Bill & Melinda Gates Foundation, and the Novo Nordisk Foundation. The U.S. National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH) in HHS, provides support in the form of in-kind services through access to a suite of preclinical services for product development. The content of this press release is solely the responsibility of the authors and does not necessarily represent the official views of any CARB-X funders.
CARB-X Contact: Marissa Novel, carbxpr@bu.edu
Rhode Island Hospital Contact: Kelly Brennan Kbrennan4@brownhealth.org, 401-895-9912
About CARB-X
CARB-X (Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) is a global non-profit partnership dedicated to supporting early-stage antibacterial research and development to address the rising threat of drug-resistant bacteria. CARB-X supports innovative therapeutics, preventatives and rapid diagnostics. CARB-X is led by Boston University and funded by a consortium of governments and foundations. CARB-X funds only projects that target drug-resistant bacteria highlighted on the CDC’s Antibiotic Resistant Threats list, or the Priority Bacterial Pathogens list published by the WHO, with a priority on those pathogens deemed Serious or Urgent on the CDC list or Critical or High on the WHO list. https://carb-x.org/ | X (formerly Twitter) @CARB_X
About Brown University Health
Formed in 1994, Brown University Health is a not-for-profit health system based in Providence, R.I. comprised of three teaching hospitals of The Warren Alpert Medical School of Brown University: Rhode Island Hospital and its Hasbro Children’s Hospital; The Miriam Hospital; and Bradley Hospital, the nation’s first psychiatric hospital for children; Newport Hospital, a community hospital offering a broad range of health services; Gateway Healthcare, the state’s largest provider of community behavioral health care; Brown Health Medical Group, the largest multi-specialty practice in Rhode Island; and Brown Health Medical Group Primary Care, a primary care driven medical practice. Brown University Health teaching hospitals are among the country’s top recipients of research funding from the National Institutes of Health. The hospitals received over $145 million in external research funding in fiscal 2023. All Brown University Health-affiliated partners are charitable organizations that depend on support from the community to provide programs and services.
About BARDA and NIAID
The U.S. Department of Health and Human Services works to enhance and protect the health and well-being of all Americans, providing for effective health and human services and fostering advances in medicine, public health, and social services. The Administration for Strategic Preparedness and Response (ASPR) leads the nation’s medical and public health preparedness for, response to and recovery from disaster and other public health emergencies. Within ASPR, the Biomedical Advanced Research and Development Authority (BARDA) invests in innovation, advanced research and development, acquisition, and manufacturing of medical countermeasures – vaccines, drugs, therapeutics, diagnostic tools, and non-pharmaceutical products – needed to combat health security threats. BARDA is one of the leading public sector funders of advanced development of antimicrobial therapeutics and diagnostics worldwide, having invested more than $2.4 billion in antimicrobial products since 2010. This investment has supported the development of over 160 antimicrobial products and led to the U.S. Food and Drug Administration (FDA) approval of four new antibiotics and FDA 510(k) clearance of eight diagnostics.
About Wellcome
Wellcome supports science to solve the urgent health challenges facing everyone. We support discovery research into life, health and wellbeing, and we’re taking on three worldwide health challenges: mental health, infectious disease and climate and health.
About the German Federal Ministry of Education and Research (BMBF)
Education and research are crucial foundations for our future. Thus, the promotion of education, science and research is a policy priority of the German Federal Government. The German Federal Ministry of Education and Research (BMBF) strengthens education at all stages of life and provides support for scientific research and innovation.
About the Global AMR Innovation Fund (GAMRIF)
The Global AMR Innovation Fund (GAMRIF) is a One Health aid fund that supports research and development around the world to reduce the threat of antimicrobial resistance (AMR) in humans, animals and the environment for the benefit of people in low- and middle-income countries (LMICs). GAMRIF core objectives are to develop innovative One Health solutions to tackle AMR; increase availability of context-specific, accessible, and affordable innovations for LMICs; establish international research partnerships with industry, academia, and governments; and collaborate with and leverage additional funding from other global donors.
About the Public Health Agency of Canada
The Public Health Agency of Canada (PHAC), established in 2004, is responsible for public health, emergency preparedness and response, and infectious and chronic disease control and prevention. Its mission is to improve the health of all people and communities in Canada by addressing public health priorities through science, innovation, service delivery, and collaborative action. The Agency collaborates closely with all levels of government, non-government organizations, and international partners to build an effective public health system. PHAC has a strong history of addressing health threats, including collaboration on a One Health approach to antimicrobial resistance (AMR). As part of the recently launched Pan-Canadian Action Plan on AMR 2023-2027, PHAC is piloting an economic pull-incentive project to increase access to essential antimicrobial drugs not yet authorized in Canada to address priority unmet public health needs.
About the Novo Nordisk Foundation
Established in Denmark in 1924, the Novo Nordisk Foundation is an enterprise foundation with philanthropic objectives. The vision of the Foundation is to improve people’s health and the sustainability of society and the planet. The Foundation’s mission is to progress research and innovation in the prevention and treatment of cardiometabolic and infectious diseases as well as to advance knowledge and solutions to support a green transformation of society.
About Boston University
Founded in 1839, Boston University is an internationally recognized institution of higher education and research. With nearly 37,000 students, it is one of the largest private residential universities in the United States. BU consists of 17 schools and colleges, along with the Faculty of Computing & Data Sciences and a number of multi-disciplinary centers and institutes integral to the University’s research and teaching mission. In 2012, BU joined the Association of American Universities (AAU), a consortium of leading research universities in the United States and Canada. For further information, please contact Kim Miragliuolo at kmira@bu.edu. www.bu.edu