Diagnostic devices to reduce the threat posed by antimicrobial resistant pathogens

Abstract

Purpose: The U.S. Department of Defense (DoD) is developing novel field-forward medical diagnostic systems to combat the threat posed by antibiotic resistant biological threat agents. The Defense Threat Reduction Agency (DTRA) is addressing this by (1) discovering host-response biomarkers that can discriminate between bacterial and viral infections, and (2) developing a system that can perform antimicrobial susceptibility testing in less than 6 hours. Methods & Materials: DTRA has partnered with industry to develop two separate medical diagnostic systems with different objectives and goals. The first device will discriminate between bacterial and viral infections by measuring the levels of three different host-based protein biomarkers in a drop of blood within 15 minutes. The second device combines single-cell rapid microfluidic channels with electrochemical detection for identification of resistant bacteria and determination of minimal inhibitory concentration (MIC). Results: Resulting data shows that the first device can measure protein biomarkers in whole blood at concentration levels ranging from μg/ml to pg/ml. Furthermore, the set of biomarkers demonstrated sensitivity and specificity of 94% and 93%, respectively. The set of biomarkers have been validated in over 10,000 patients in multiple studies between 2009 and 2018. The second device showed real-time single-cell antimicrobial susceptibility testing by measuring growth activity in the presence of varying concentrations of different antibiotics. Preliminary data demonstrated that E.coli was inhibited in the presence of clinically relevant levels of ampicillin versus non-inhibited E.coli in control broth. In addition, MIC was obtained in less than 6 hours versus that of more traditional methods (24–48 hours). Conclusion: While both of these systems are in various stages of research and development, DTRA's goal is to seek U.S. Food and Drug Administration clearance within the next 3 years. Both devices support antibiotic stewardship and inform better medical treatment using different tactics. The success of these two complimentary approaches will significantly impact the way the DoD and public health sector combats threats posed by antibiotic and multi-drug resistant bacteria.