Rapid antimicrobial susceptibility testing directly from urine specimens

Rapid antimicrobial susceptibility testing directly from patient specimens Abstract Each year, 20 million patients are diagnosed with infections leading to over 100,000 deaths and costing the US healthcare system about $70B. Antibiotic resistant infections are increasingly common, causing about 3 million infections and 35,000 deaths annually in the US. Patients, even those with life-threatening infections, can be quickly cured if, near the onset of infection, they can be treated with an antibiotic that specifically targets the pathogen causing the infection. Unfortunately, today’s diagnostic methods require 2-4 days to determine tar- geted, or definitive, therapies. For this reason, physicians must treat patients empirically using broad-spectrum antibiotics that are often less effective than definitive treatments and sometimes even completely ineffective. Furthermore, treatment with these powerful drugs causes the spread of antibiotic resistance. This is exacerbated by the fact that at least 30% of antibiotics are prescribed unnecessarily to patients that are in fact uninfected. Current antimicrobial susceptibility testing methods for determining the definitive therapies take days to deliver results because they require multiple lengthy steps including a day-long step to purify the pathogen cells in large numbers by microbiological culture. This proposal develops novel products that detect whether patients are in- fected, identify the pathogen in 30 minutes, and determine the definitive treatment in just a few hours rather than the days required today. The proposed tests thus have the potential to dramatically improve patient out- comes and attenuate the spread of resistance. The new tests identify (ID) pathogens and perform antimicrobial susceptibility testing (AST) directly from patient specimens, eliminating the lengthy culture steps required by the current methods. The novel MultiPath technology underlying the tests uses inexpensive digital imaging to rapidly, sensitively, and affordably count individual microscopic bacterial cells without magnification. The MultiPath AST tests can determine the definitive treatment for a much broader range of infections than other emerging rapid susceptibility methods because they can determine antimicrobial susceptibility for specimens with commensal bacteria and from patients with polymicrobial infections. The easy-to-use tests run on the automated random- access MultiPath analyzer that is currently under regulatory review. This Phase II proposal develops rapid ID and AST tests for urinary tract infections (UTIs). UTIs account for about half of all infections which are increasingly caused by resistant pathogens. The proposed work builds on work presented in the preliminary results demon- strating the feasibility of AST directly from urine specimens. Specifically, we will (1) Complete UTI ID/AST product development; (2) Complete alpha UTI/AST analytical and preclinical studies; and (3) Complete external beta pre- clinical studies and prepare for regulatory submission. Completion of the proposed project will deliver MultiPath UTI ID/AST tests ready for verification and validation studies for regulatory submission in Phase III.