Novel Bone Cement May Prevent Amputations Due to Osteomyelitis

baumannii strains isolated directly from soldiers wounded in Iran and Afghanistan. The mice were then treated with either colistin by injection, local colistin via Plexiglass (Polymethyl methacrylate, PMMA) bead bone cement, or a bone cement control with no drug. The 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. The researchers then confirmed that all study mice were infected with the bacteria, and that 75% of the strains were resistant to multiple antibiotics. The researchers found that the bone cement containing colistin significantly reduced the infection rate, so that only 29.2% of mice had detectable levels of parC after 19 days. Importantly, Colistin via injection failed to control the infection and was no better than placebo.

The researchers also took the first close look at the effect of A. baumannii and Staphylococcus aureus OM 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. The researchers found, surprisingly, that in contrast to S. aureus OM, which is osteolytic and characterized by biofilm in necrotic bone, A. baumannii OM results in blastic (bone forming) lesions that do not contain apparent biofilm.

"Perhaps 2,000 soldiers come into field hospitals with compound fractures each year that become infected with A. baumannii,” said lead author Edward Schwarz, Ph.D., a professor of orthopedics in the center for musculoskeletal research at URMC. "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.”

Osteomyelitis is a bone infection caused by various bacteria, and usually occurs in severe fractures when bone is exposed to open air. Although A. baumannii rarely causes OM in the United States, it is very prevalent in the Middle East, and is now present in more than 30% of soldiers recovering from open fractures in field hospitals in Iraq and Afghanistan. Outbreaks of the infection started among American soldiers returning from Iraq in 2003. 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 S. aureus (MRSA), which recently surpassed HIV as the most deadly pathogen in the United States, despite nearly universal use of the best available antibiotics.

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University of Rochester Medical Center