(CRE), multidrug-resistant (MDR) Acinetobacter
, and MDR Pseudomonas aeruginosa
continue to pose significant clinical challenges around the world.
Although their prevalence can be hard to quantify, given inconsistent reporting requirements from state to state and country to country, it is known that these bacteria are resistant to many of the key drugs available to treat infections, leading to severe illness and, in some cases, death in a growing number of patients.
Since the first case of Klebsiella pneumoniae
carbapenemase-producing CRE was identified in North Carolina in 2001, for example, it has been reported in almost every US state and is now “the carbapenemase most commonly identified in isolates sent to the Centers for Disease Control and Prevention (CDC), according to a study
published in 2015 in the Journal of the American Medical Association
MDR Pseudomonas aeruginosa
is even more common than CRE, having been linked with 22% of pneumonia cases and 14% of bloodstream infection cases in the United States, based on the findings of a meta-analysis
published in 2013. And, although the prevalence MDR Acinetobacter
remains relatively small, identified strains of these bacteria have been found
to be resistant to more than 50% of the drugs (in multiple classes) available to treat them.
However, clinicians treating these so-called “superbugs
” may soon have more options available to them, at least if the US National Institute of Allergy and Infectious Diseases (NIAID) has its way. On January 8th, the federal agency, which is part of the National Institutes of Health, announced plans to fund research projects designed to discover and develop new antibiotics to treat these troublesome bacteria.
“The purpose of this Funding Opportunity Announcement is to support milestone-driven projects focused on developing and utilizing novel predictive assays, models, and/or research tools based on penetration and efflux of small molecules to facilitate therapeutic discovery for select Gram-negative Pseudomonas aeruginosa
,” the NIAID document
Interested research institutions and/or groups have until April 17th to submit a letter of intent to the agency; final applications are due May 17th. NIAID plans to commit $9 million to fund 10 to 15 projects in 2018. To be eligible for a funding award, research projects must be “milestone-driven” to ensure that the objectives are practical and realistic. The agency is hoping to receive applications from multidisciplinary teams working in academic settings and in collaboration with industry partners.
“In recent years, several public forums (including NIAID-sponsored workshops) identified our lack of understanding of the principles that govern compound penetration into and efflux out of Gram-negative bacteria as a key bottleneck for the rational discovery of novel lead therapeutic compounds,” the funding announcement reads. “The paucity of suitable assays/tools/models to inform structure-activity relationships and guide optimization of whole cell penetration (and efflux avoidance) is reflected in the failure of medicinal chemistry efforts to advance novel chemical classes of compounds with Gram-negative activity. As more Gram-negative bacteria become resistant to antimicrobials and therapeutic options become limited or nonexistent, it becomes imperative to understand and rationalize the principles that allow molecules to penetrate Gram-negative bacteria while avoiding efflux and overt toxicity toward eukaryotic cells. Therefore, developing new assays, tools, and models is paramount for overcoming this key bottleneck and facilitating the development of novel compounds targeting Gram-negative pathogens.”
Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.
To stay informed on the latest in infectious disease news and developments, please sign up for our weekly newsletter.