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 >60% 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, 10-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.
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.
| Tarlton, Nicole J; Satoorian, Tiffany S; Panchal, Anand et al. (2018) Monoclonal antibody-mediated detection of CTX-M ?-lactamases in Gram-negative bacteria. J Microbiol Methods 144:37-43 |
