R01AI182314

Form with function: Rapid phenotypic carbapenemase testing to improve detection of carbapenemase-producing organisms - Project abstract

Infections due to carbapenemase-producing organisms (CPOs) are associated with high mortality rates due to extensive antibiotic resistance, and carbapenemase genes can be transferred between bacteria leading to outbreaks.

Therefore, CPO identification has significant implications for antibiotic selection and use of infection control practices in healthcare facilities.

No antibiotic susceptibility test profile accurately identifies CPO.

Yet, existing methods for CPO detection, including phenotypic, molecular, and lateral flow assays, are not performed by most clinical microbiology laboratories due to test complexity, prolonged workflows, subjective results, reagent instability, and high cost.

Phenotypic tests have many key features necessary for a general CPO screen, yet logistical barriers still prevent their widespread adoption.

The objective of the current proposal is to evaluate the potential impact of rapid CPO detection using a form-factor optimized phenotypic test paired with machine learning algorithms to distinguish carbapenemase gene families at the time of GNB identification.

Our central hypothesis is that a rapid, low-cost phenotypic test will increase CPO detection, decrease time-to-identification of a CPO infection, and facilitate timely initiation of effective antibiotics and isolation practices.

Rapid CPO detection will be achieved with a phenotypic test optimized by our group (the MCNP) and ported into a structurally-programmed sticker microfluidic to perform four discrete reactions in a single channel (the μCNP).

These assays provide objective carbapenemase detection in ~20 minutes and will be used to achieve the objectives of this proposal, as laid out in three aims.

1) Distinguish carbapenemase class and gene family using machine learning. This aim is based on the capacity of machine learning to identify subtle changes over time in the colorimetric MCNP test and provide objective, automated results to the carbapenemase class and gene-family level.

2) Evaluate rapid phenotypic detection of CPO in the μCNP, which will provide reproducible and stable carbapenemase detection in a low-cost, scalable sticker microfluidic that replicates MCNP performance.

And 3) Compare rapid carbapenemase detection to standard-of-care testing by leveraging active protocols for collection of clinical cultures and ongoing studies of CPO carriage and healthcare environmental contamination.

Rapid CPO testing will increase overall CPO detection and decrease time to identification from GNB-positive cultures and surveillance rectal swabs.

Expected results include the demonstration of the utility of the μCNP as an accessible phenotypic carbapenemase test for appropriate antibiotic selection and rapid identification of CPO-colonized individuals for timely contact isolation.

We envisage an important positive impact as our platform will provide equitable access to carbapenemase testing, improve patient outcomes, and prevent CPO outbreaks in healthcare networks.

Emory University

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Georgia United States

State-Wide

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)