DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Rapid Microbiological Diagnostics for MDRO Quantitative Identification and Resistance Phenotyping To Guide Antibiotic Selection in Wounded Warriors and Veterans

Principal Investigator: PRICE, CONNIE
Institution Receiving Award: DENVER HEALTH
Program: DMRDP
Proposal Number: DM110148
Award Number: W81XWH-12-2-0085
Funding Mechanism: Military Infectious Diseases Applied Research Award
Partnering Awards:
Award Amount: $1,870,207.75


PUBLIC ABSTRACT

Military service members and the U.S. Veteran population face a growing and serious health threat: widespread antibiotic resistance resulting from resistant bacteria and a dwindling pipeline of sufficiently potent antibiotics. Infections with antibiotic-resistant bacteria are increasing significantly. They cause major complications and mortality, and drive up healthcare costs. Powerful but non-targeted antibiotics, while in widespread use, can actually pressure bacteria to develop resistance.

Current methods for diagnosing infections typically require 2-3 days to produce results that can guide antibiotic choice. That is frequently too delayed to help clinicians make good treatment decisions. This also results in inappropriate or over-treatment with non-targeted antibiotics that are started while awaiting lab results. More rapid technologies that can accurately diagnose the specific cause of an infection could guide early, targeted antibiotic treatment. This would result in more effective early treatment of infection, decrease unnecessary exposure to excess antibiotics, and could slow the development of antibiotic resistance. By diagnosing infections earlier, we expect to reduce the complications and mortality of combat-related infections in Wounded Warriors and Military Veterans. This should occur (a) by decreasing exposure to toxic antibiotics and their associated side effects and/or (b) by increasing prescribing of therapy that works against the infection more quickly after diagnosis.

We propose a new ultra-rapid technology that uses a digital microscope to detect bacteria growing directly from a patient's specimen, rather than waiting for growth in lab cultures. The innovative new method supports identification of the infecting bacteria within 2 hours of receiving a specimen. The technology also shows the effect of selected antibiotics on the bacteria including multidrug-resistant bacteria so that doctors know within 6 hours from specimen collection which antibiotic kills the bacteria.

The study will determine the accuracy and speed of the new technology in identifying infections from blood, lung, and wound specimens compared to current techniques. Then, in a simulation experiment, the study will compare antibiotic choices that might have been made using the new technology with those actually prescribed during the patient's clinical care. This simulation is intended to demonstrate that the new technology will result in appropriate initial antibiotic prescribing but decrease excessive exposure to antibiotics.

Specimens will be acquired from patients during their usual course of care from Civilian (Denver Health, and Washington Hospital Center) and a Veterans Administration Hospital (Denver VA).

Reducing therapeutic failures and non-targeted antibiotic treatment would not only reduce risk of significant complications and mortality in wounded warriors and veterans, but also in civilian populations. The new approach could also help to conserve antibiotic effectiveness by reducing excessive antibiotic use during the much shorter wait for laboratory results to help guide drug choice.