Osteomyelitis (OM) is a dangerous bacterial bone infection that often occurs in patients with open fractures. So it is not surprising that injured American soldiers serving in Afghanistan and Iraq have been getting OM, with an end result sometimes being a limb amputation. Now researchers from the Center for Musculoskeletal Research in Rochester with help from the Department of Orthopedics at Aarhus University Hospital in Denmark, Infectious Disease Service at Brooke Army Medical Center in San Antonio, and Heraeus Medical GmbH, created a new colistin-infused bone cement that is showing itself to be effective against the variety of bacterial pathogens that cause OM. Interestingly, Stryker already has a bone cement that features colistin, a product called Simplex P with Erythromycin & Colistin.
From a press statement by the University of Rochester Medical Center:
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.”
Approaches commonly used to overcome MDR [multi-drug resistant] 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.
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.