DoD Aids Research on Identification of Pathogens in Hours, Not Days

Technology Also Helps Determine Most-Effective Antibiotics

By Brenda L. Mooney

The DoD’s involvement with the development of new technology to rapidly identify pathogens and appropriate antibiotic therapy has its roots in the Iraq and Afghanistan wars. Transporting wounded warriors increased survival rates but also raised the likelihood that those servicemembers received inappropriate antibiotics.

DENVER—U.S. warfighters injured in combat in Iraq and Afghanistan had a remarkable 90% or more rate of survival, with much of that success credited to a medical evacuation system that quickly transported them to locations such as Landstuhl Regional Medical Center in Germany or to Brooke Army Medical Center in Texas.

The unexpected consequence, however, was the dramatic increase in opportunities for those wounded warriors, who traveled thousands of miles during days of being treated, to acquire opportunistic infections. Study after study documents how those patients, often suffering from polytrauma, were then prescribed antibiotics—sometimes inappropriate—based on the best guess of a physician they might see once. The result: Greater antibiotic resistance.

Although there weren’t many other options at the time, the history helps explain why the need for rapid identification of pathogens is so important to the U. S. military, which also faces the risk of bioterrorism or biological weaponry in future conflicts.

“Wounded warriors (WW) have a high rate of combat-associated infections that, because of their debilitated state, can become life- or limb-threatening if not treated appropriately within a few hours of symptom onset,” wrote Connie Price, MD, of the Denver Health and Hospital Authority in a technical abstract seeking funding from the Congressionally Directed Medical Research Programs (CDMRP). “Conventional laboratory cultures require 2-3 days to produce results that can guide antibiotic selection, which is too late to affect outcomes. Adverse events (AEs), such as drug toxicity and/or Clostridium difficile infection, from use of overly broad-spectrum antimicrobial agents while awaiting cultures adds to the associated morbidity and mortality.”

A contingency air staging facility medical team carries a wounded servicemember off a C-17 Globemaster III at Ramstein Air Base, Germany, after a recent flight from Balad Air Base, Iraq. Medics then transport patients to nearby Landstuhl Regional Medical Center for further treatment and recovery. (U.S. Air Force photo/David Kellogg)

Price’s research focuses on more rapid technologies to accurately diagnose the specific cause of an infection and to allow better 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,” she added.

The technology she proposed—multiplexed automated digital microscopy (MADM)—has shown success in preclinical research in identifying and quantifying multiple pathogens within two hours. The effect of selected antibiotics on the bacteria, including multidrug-resistant pathogens, allows clinicians to determine within six hours from specimen collection what agent to employ.

The equation is fairly straightforward, as Price told U.S. Medicine, “More rapid identification of antimicrobial resistance equals earlier appropriate therapy and/or de-escalation to more narrow spectrum therapy to avoid development of antimicrobial resistance.”

Since the 2012 funding of the grant, she and her study team have validated and identified within an hour a number of bacterial species including S. aureus, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter cloacae, Acinetobacter baumannii and Pseudomonas aeruginosa with sensitivity and specificity of at least 97% in blood cultures, according to CDMRP.

Also performed, the agency noted, was “antibiotic susceptibility testing with specific minimum inhibitory concentration within 5 hours for methicillin vs. S. aureus, ciprofloxacin, imipenem, amikacin and minocycline vs. A. baumanii and ciprofloxacin and amikacin vs. P. aeruginosa.”

Price has been working with an industry partner, Accelerate Diagnostics Inc., which received approval from the Food and Drug Administration in February to allow marketing of the PhenoTest BC Kit, performed on the Pheno System.

“The digital microscopy platform we studied in our DoD work ultimately became the FDA-approved Pheno system,” Price pointed out.

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