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NEW TWIST ON OLD
MEDICAL TECHNOLOGY MAY PREVENT
AMPUTATIONS FOR MANY GIs -- A special
antibiotic mixed
with a common bone cement could lead to
control of
Acinetobacter baumannii, thus reducing
amputations.

Acinetobacter baumannii is deadly... and it
is coming home with our troops. For more on Ab, use the VA Watchdog
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nology_may_prevent_amputations.html
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New twist on old
medical technology may prevent amputations
Infection now widespread among soldiers wounded in Iraq and Afghanistan
Old 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 Afghanistan, and as evidence emerges that the
infection studied may set the stage for more dangerous infections that can
lead to amputation.
Osteomyelitis is (OM) a bone infection caused by various bacteria, and
usually occurs in severe fractures when bone is exposed to open air.
Although Acinetobacter baumannii rarely causes OM in the United States, it
is very prevalent in the Middle East, and is now present in more than 30
percent of soldiers recovering from open fractures in field hospitals in
Iraq and Afghanistan. Past studies have established that one in four
severe war wounds in Iraq is a fracture, more than 80 percent of which are
open, where the bone is exposed to airborne bacteria.
Not common in the United States and not potentially fatal, A. baumannii OM
had been largely ignored until recently by physicians and the
pharmaceutical industry, which focuses on life-threatening infections that
affect millions, not hundreds. Then military outbreaks of the infection
started among American soldiers returning from Iraq in 2003, with the
number of A. baumannii OM infections seen in field hospitals, and in
stateside facilities receiving injured soldiers, growing. At the same
time, data began to emerge from hospitals treating soldiers suggesting
that easily contracted A. baumannii may be arriving first at the fracture
site and "priming" it so that it becomes more vulnerable to methicillin-resistant
Staphylococcus aureus (MRSA), which recently surpassed HIV as the most
deadly pathogen in the United States despite nearly universal use of the
best available antibiotics.
"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, Ph.D., professor of Orthopaedics 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
orthopaedic, 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 U.S. 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
Iran and Afghanistan. The mice were then treated with either colistin by
injection, local colistin via PMMA bead bone cement or a bone cement
control with no drug. Researchers measured the amount of bacteria in the
mice as they responded to treatment with a new test of parC gene activity,
a gene known to be present only in A. baumannii. Experiments confirmed
that all study mice were infected with the bacteria, and that 75 percent
of the strains were resistant to multiple antibiotics. Importantly, the
bone cement containing colistin significantly reduced the infection rate
such that only 29.2 percent of mice had detectable levels of parC after 19
days (p< 0.05 vs. i.m. colistin and placebo). Colistin via injection
failed to control the infection and was no better than placebo.
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 Rochester, along with Kjeld S�balle from the
Department of Orthopedics at Aarhus University Hospital in Denmark.
Christian Wahnes and Hubert Büchner led the effort within Research &
Development with Heraeus Medical GmbH, which donated the colistin for
testing. Clinton Murray of the Infectious Disease Service at Brooke Army
Medical Center in San Antonio made available to researchers the strains of
A. baumannii taken from soldiers. The work was supported by research
grants from the U.S. Army Medical Research Acquisition Activity (USAMRAA)
Orthopaedic Trauma Research Program, and the National Institutes of Health
Public Health Service Awards.
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.
University of Rochester Medical Center
-------------------------
posted by Larry Scott
Founder and Editor
VA Watchdog dot Org
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