Healing warriors by making a census of combat wounds' microbiota
After an American GI is wounded in combat, his or her life depends on the speed of evacuation, the degree to which blood loss can be stanched, and the skill with which military surgeons can clean, patch and stitch.
But it also depends on a factor that's even harder to predict, especially when a wound has been inflicted on foreign soil and in the fog of war: the microorganisms — viruses, bacteria and fungi — that find their way into the servicemember's wound and take up residence there.
New research suggests that physicians treating future U.S. troops (and perhaps those treating some of today's wounded warriors) may be able to take a fast and thorough census of the microorganisms living in a combat wound and tailor their treatment accordingly.
The result could mean not only speedier and more thorough healing, but fewer limbs — and lives — lost to postsurgical infection. For civilians suffering from traumatic injury, burns, diabetic sores and other complex wounds, the new research may also prove lifesaving.
In a study published online in the Journal of Clinical Microbiology (and slated for the journal's July print edition), a group of physicians, microbiologists, geneticists and technology experts describe a system capable of comparing the DNA of microorganisms colonizing a wound with a vast library of stored viral, bacterial and fungal genetic sequences.
A research team from Lawrence Livermore National Laboratory, UC Davis and the Uniformed Services University of the Health Sciences evaluated 124 wound samples from 44 U.S. troops wounded in Iraq and Afghanistan.
Within 24 hours of a tissue sample's arrival at Lawrence Livermore, the system of microarrays described in the research was able to sort through some 8,100 microorganisms that had previously been genetically sequenced to find matches for microbes thriving in a wound.
The research was funded by the Defense Department's Medical Research and Development Program.
If such a system of computerized genetic interrogation could be made fast, economical and widely available, it would mark a radical change from current practice. Currently, the microbes in burns and traumatic wounds are painstakingly collected and, one by one, cultured in a dish so that physicians can guess at which antibiotics or anti-fungals might prove useful. Not all microbes are so easily grown in a lab, and thus go undetected.
But a microbe's DNA fingerprint, captured on a chip, won't elude detection.
By identifying a wound's colony of microbes faster and more thoroughly and by potentially tracking a colony's shifting composition, the "microbial detection array" developed at Lawrence Livermore could guide the use of targeted antimicrobial medicines to drive down infection and even promote healing, the authors said.
Study co-author Dr. Eric Elster, professor and chairman of the Uniformed Services University’s surgery department, said the method of determining which microbes are present in a wound is a century old. It is far too crude to allow inferences to be drawn about the roles that particular strains may play in promoting healing or the chronic inflammatory response that can impede it, he said. And for those wounded in combat, it's a particularly clunky method of gleaning information that could guide better treatment.
Over the last decade alone, fatalities among troops wounded in combat have fallen from nearly 16 percent to about 6 percent, despite wounds that are more serious and extensive, Elster said, who said that "the injury patterns that we are presented with are among the most complex and challenging seen in modern medicine.”
“The treatment of infection in these patients requires innovative care," he said. "Studies such as this one will allow us to better understand the interaction between the body and pathogens, and develop new treatment strategies.”
A growing body of research has begun to demonstrate that the diverse populations of microorganisms that coexist in our guts, on our skin, in our mouths and around the genitals are not just incubators of infection but a competing and ever-changing mix of good and bad microbes, more complex than long believed. In that vein, the researchers sought to detect classes of microorganisms that were present in wounds that heal readily and others that signal a wound will require more aggressive care.
While the sample of wounds was small and the findings preliminary, the authors found that when bacteria such as the Pseudomonas species and Acinetobacter baumannii, which are common hospital-related infections, were present in wound samples, they were less likely to heal well.
By contrast, the robust presence of bacteria often related to the gastrointestinal system, such as E. coli and strains of the Bacteroides species, were associated more frequently with wounds that did heal well.
Livermore Labs microbiologist Nicholas Be, the lead author of the study, said the preliminary finding fell far short of suggesting that adding certain bacteria to a patient's wound could promote healing. But "it certainly is an indication that tracking or manipulating the bacterial population of wounds might come into play" in a patient's treatment.
"We’re trying to create a more informative diagnostic — one that might allow personalizing treatment to an individual" with extensive burns or wounds that are massive or heal slowly, Be said.