NIAID Grants Highlight Innovations in HAI and AST Testing

NIAID Grants Highlight Innovations in HAI and AST Testing

The National Institute of Allergy and Infectious Diseases (NIAID) (part of the National Institutes of Health [NIH]) provided grants totaling more than $11 million to nine research projects for the development of diagnostic tests for antibiotic-resistant bacteria. Commonly referred to as bacterial identification and antibiotic susceptibility testing (ID/AST), the traditional test format uses culture media to identify (ID) pathogens through substrate reactions indicative of metabolism or enzymatic activity specific to the species or strain. Panels or other specialized cultures are then used to determine the resistance or susceptibility to applied antibiotics through the observation of cultured growth (or lack thereof). The critical nature of drug-resistance hospital-acquired infections (HAIs) has pressured ID/AST testing times; timely results are need to implement alternative treatments for infected patients before the spread of infection to the bloodstream or the possible onset of sepsis. In light of recent HAI outbreaks at U.S. health facilities, the NIAID and other government authorities are supporting research into rapid, multiplexed and effective tests using alternative methods to traditional culturing. The following review highlights some NIAID grant recipients with notable test platforms, including commercialized rapid molecular platforms and innovative research tools emerging from academic and industry research programs. The majority of grants were for carbapenem-resistant Enterobacteriaceae (CRE), bloodstream infection, and urinary tract infection testing.

The least surprising name among grantees was BioFire Diagnostics. The bioMérieux subsidiary offers a powerful, leading near-patient or point-of-care (POC) infectious molecular test platform, the FilmArray. The product is already used among hospitals with an FDA-cleared Blood Culture Identification (BCID) panel able to identify numerous HAI pathogens as well as the antibiotic resistance genes mecA (methicillin), vanA/B (vancomycin) and KPC (carpagenem). Results from blood cultures are available in an hour using the FilmArray BCID panel, though results are not as timely as desired for patient treatment as time-consuming culturing of patient blood samples remains a prerequisite. BioFire received a grant to develop a FilmArray Sepsis Direct Panel sensitive enough to detect HAI pathogens and 16 drug resistance genes directly from lysed, centrifuged patient blood. Achieving higher sensitivity with nucleic acid-based tests in direct blood samples is a major challenge addressed by grant recipients.

With clinical partner the Denver Health and Hospital Authority, Accelerate Diagnostics will look to field test its imaging-based Accelerate ID/AST system. The system bypasses culturing and nucleic acid amplification procedures to provide pathogen identification in one hour and AST results in 3 hours. The cell imaging platform extracts bacterial cells from patient blood and micropipettes them in up to 48 cassette-held flowcell channels. The cassette’s active flow cells are scanned and the images used for automated analysis, including the identification of bacterial cells and the detection or inhibition of growth depending upon chosen flowcell conditions (presence of specific antibiotics). Microscopic imaging significantly reduces analysis time by eliminating the need for extensive culturing.

First Light Biosciences has applied its no-magnification cell imaging system to urinary tract infection (UTI) testing. The MultiPath platform uses selective fluorescent immuoreagents to register the microscopic growth of UTI pathogens illuminated by a specialized lamp. Fluorescence is registered by photosensitive pixels with the entire testing process contained within a cartridge. The MultiPath UTI ID test will quantitatively detect 9 of the most common UTI pathogens in as little as 15 minutes. Pathogen detection is followed by an AST test with results provided in 3 hours.

A research collaboration including Johns Hopkins University, Stanford University, the University of Arizona and General Electric (GE) Global Research also seeks to bypass amplification in molecular testing for HAIs. The novel molecular approach uses microfluidics to produce millions of picoliter-sized droplets able to encapsulate individual bacterial cell and probe or cell and antibiotic mixtures for ID and AST testing. The developmental approach allows for direct testing of urine samples.

The Broad Institute of the Massachusetts Institute of Technology (MIT) and Harvard University was a grant recipient for its unique molecular test concept based on RNA hybridization. More specific pathogen identification will be accomplished through the detection of ribosomal RNA sequences. Antibiotic susceptibility, rather than resistance, will be determined through molecular probe hybridization with transcripted cellular RNA that is a more rapid indicator of bacterial response to antibiotics than changes in cultured growth. Higher volumes of intracellular RNA for testing and microfluidics can eliminate the need for amplification. The Broad Institute’s approach is unique and potentially more accurate in determining resistance by not relying on known drug resistance gene sequences and being able to detect resistance through unknown mutations or cellular pathways.

The above projects all seek to shorten time to results using alternatives to culturing, including no-amplification molecular probe hybridization or detection without prior culturing. As demonstrated by public involvement, ID/AST testing at health facilities is critical not only to individual patient treatment, but initiated an effective institutional response to HAI contamination. Concerns over pathogen drug resistance has already delivered a significant hospital molecular diagnostics market, and outstanding demand for faster HAI test results is likely to bring further diagnostics investment outside of central labs.

Kalorama Information offers market research reports relevant to HAI testing including The Market for Hospital-Acquired Infection Control (Sterilization, Disinfection, Testing and Treatment and The World Market for Infectious Disease Diagnostic Tests.