Old medical technologies, bone cement and a well known antibiotic, may effectively fight an emerging infection in soldiers with compound bone fractures, according to a study published online today in the Journal of Orthopedic Research. An urgent search for solutions is underway as 20,000 additional American soldiers head for
Not common in the
"If you apply the findings from two small studies to the entire U.S. military, which is a leap, perhaps 2,000 soldiers come into field hospitals with compound fractures each year that become infected with A. baumannii," said Edward Schwarz, PhD, professor of orthopedics within the Center for Musculoskeletal Research at the University of Rochester Medical Center. "About a third of them go on to get a staph infection after they reach the hospital, with about a third of those, perhaps 200 soldiers, suffering infectious complications that could cost them a limb. Studies already underway in our lab seek to clarify how the initial infections could gradually be replaced by catastrophic MRSA, and to prove that we can save limbs by putting an established antibiotic into bone cement for the first time."
Current antibiotics often kill a strain of bacteria responsible for a disease, only to create a vacuum quickly filled by related strains. The widespread overprescribing of antibiotics and the speed of bacterial evolution have greatly increased the likelihood that the strains most able to resist antibiotics will thrive. Multi-drug resistant (MDR) bacterial strains are now widespread in all hospitals.
MDR strains tend to cluster in hospitals, where patients may pass the infection to each other no matter how sterile the environment, although the exact cause is not known. Multi-drug resistant Acinetobacter baumannii (MDRAB) infections is oftentimes treated with an older class of drugs known as polymyxins, including colistin, one of the last-resort antibiotics for multidrug resistant A. baumannii. Approaches commonly used to overcome MDR infections after orthopaedic injuries include applying a large dose of antibiotic locally to the site of infection via bone cement. Bone cements composed of Plexiglas (polymethyl methacrylate or PMMA) have been used for decades for plastic surgery, to anchor in bone prostheses and to fill in holes in bone caused by trauma. Such materials became even more useful when researchers realized decades ago that they could load them with antibiotics to deliver large doses of drug directly to the injury site without subjecting the whole body to toxic levels of antibiotic. While bone cements laced antibiotics against staph and strep infections are common (e.g. vancomycin), no group had ever developed a bone cement treatment using colistin against A. baumannii.
To begin the process of providing such a treatment for soldiers, a team of orthopedic, military and pharmaceutical researchers came together to conduct the current study, the results of which argue for a human clinical trial with colistin-laced bone cement, researchers said. Such a trial would likely proceed within the military medical system, where treatments for maladies suffered specifically by the troops are pursued under military research contracts, which use with the same standard required by the Food and Drug Administration when approving medications and devices for civilian use.
Schwarz and colleagues developed a group of mice infected with drug resistant A. baumannii strains isolated directly from soldiers wounded in
Along with Schwarz, Daniel Crane, Kirill Gromov, Dan Li, Matthew Hilton and Regis O'Keefe led the study effort within the Center for Musculoskeletal Research in
The team also took the first close look at the effect of A. baumannii and S. aureus osteomyletis on bone biochemistry. When bacteria infect bone, they uncouple delicately balanced biochemical signaling responsible for the recycling of bone to preserve its strength, typically resulting in bone loss (osteolysis) that can be seen as a hole on X-rays. In the current study, researchers found that staph infection did indeed encourage bone breakdown, but were surprised to find that A. baumannii infection did the opposite, encouraging bone formation.
"These findings have implications for clinical care, as imaging technologies that capture unusual bone cell growth may be used to diagnose A. baumannii earlier," Schwarz said.