Rapid Immunodiagnosis of Drug-Resistant Bacterial Pathogens

DESCRIPTION provided by applicant Bacterial resistance to lactam antibiotics is threatening to limit the effectiveness of this most used class of antibiotics A major contributin factor to this problem is the lack of rapid testing methods for medical practitioners to identify lactam resistant pathogens before prescribing specific antibiotics For urinary tract infections UTIs the most common bacterial infections in the world older lactam antibiotics are not used despite the fact that andgt of uropathogens are sensitive to these drugs Resistance to lactam antibiotics is conferred by the expression of lactamases enzymes that deactivate the antibiotics We propose the development of a rapid immunoassay test kit for detection of any of a wide range of lactamases In Phase I of this project we aim to develop cross reactive monoclonal antibodies MAbs targeting the homologous regions of the most clinically problematic classes of lactamases extended spectrum lactamases ESBLs and carbapenemases and then to develop a sandwich ELISA capable of distinguishing lactam resistant clinical bacterial isolates from lactam sensitive isolates In Phase II we will aim to convert this laboratory ELISA into a robust minute lateral flow immunoassay test kit similar to the home pregnancy test capable of detecting lactamases and therefore lactam resistance directly in patient samples This capability promises to revolutionize current clinical practice for treatment of UTIs allowing the effective use of even the earliest lactams and preventing the selection of resistance to current first line treatments PUBLIC HEALTH RELEVANCE A major contributing factor to the problem of bacterial resistance to antibiotics is the lack of rapid testing methods for medical practitioners to identif lactam resistant pathogens before prescribing specific antibiotics We propose the development of a rapid test kit to detect resistance to lactam antibiotics directly in urine samples of patients with urinary tract infections This capability promises to allow the targeted use of antibiotics on sensitive pathogens resurrecting the effectiveness of older drugs and preventing the selection of resistance to current first line treatments