Rapid Immunodiagnosis of Drug-Resistant Bacterial Pathogens

项目总结/文摘

PROJECT SUMMARY/ABSTRACT This proposal describes Phase II of the development of a rapid immunoassay test kit for the determination of β-lactam antibiotic resistance, to be used as a point-of-care diagnostic test for urinary tract infections. Today, antibiotics for UTI are prescribed empirically, with no diagnostics available to clinicians to avoid treating resistant infections with the very drug to which the pathogens are resistant. This problem has resulted in ever-increasing prevalence of resistance, rendering many drugs unusable. The proposed test kit will be a lateral flow immunoassay, similar in principle to a home pregnancy test. The test design is based on monoclonal antibodies specific for β- lactamases, the enzymes conferring resistance to β-lactam antibiotics. In Phase I, the applicant developed a working assay capable of distinguishing β-lactam-resistant bacteria from β-lactam-sensitive isolates. In Phase II, this assay will be converted into a simple 20-minute test kit, and a complete manufacturable product will be developed. Clinical validation studies will be carried out to determine the real-world performance of the product. At the successful conclusion of Phase II, we expect to demonstrate a rapid, simple, and accurate test for β-lactam resistance in UTI, enabling clinicians to test unprocessed urine samples and determine the optimal antibiotics based on the results. This capability promises to revolutionize the management of bacterial UTIs, giving clinicians the ability to selectively prescribe older β-lactam antibiotics to test-neagtive patients with a high confidence of efficacy. Such treatment is expected to improve outcomes for patients while dramatically reducing the empiric use of broad-spectrum antibiotics.