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Study shows vancomycin powder may increase the risk of spine nonunions
Researchers found high doses of the powder may also reduce osteoblast migration at the fusion site, thus impeding bone union.
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Surgical site infection is a major complication of spine surgery, and vancomycin powder reportedly can reduce infection rates, but a study of this material showed it may be a detriment to bone union during spine fusion and may also inhibit cell migration and proliferation.
Claudia Eder, MD, and colleagues from Vienna evaluated the effects of vancomycin powder in incubated bone samples placed in Dulbecco’s Modified Eagle’s Medium supplemented with 10% fetal calf serum, 2 mM L-glutamine, 0.05 mg/ml ascorbic acid and 50 μg/ml gentamycin. These were compared with cultures with vancomycin added to a concentration of 3 mg/cm2, 6 mg/cm2 or 12 mg/cm2.
Claudia Eder
“If you want to get spinal fusion, you have to get cells into the intervertebral disc space so the cells have to be able to migrate. Osteoblast migration success was 100% in our control samples, and we noted the migration of cells from bone tissue onto the culture dish after approximately 3 days,” Eder said at the EuroSpine Annual Meeting, in Lyon, France
May reduce osteoblast migration
“Osteoblast migration was reduced to 44% in the lowest dose group, 33% in the mid-dose group and there was not a single osteoblast migrating in the highest dose group. So, powder application results in a dose-dependent suppression of osteoblast migration,” she said.
Migration of osteoblasts was observed in the control medium after an average of 3 days and was significantly delayed after vancomycin treatmen, Eder said.
Cell counts were significantly reduced in the mid- and high-dosage groups, she said.
Cell death with high dose
In addition, average cell viability was 99% in the control media and 96% in the low-dose group, but the viability declined to 94% in the medium-dose group and to 76% in the high-dose group, Eder said.
This means that about one-fourth of the viable cells in the high-dose culture died within 24 hours of being surrounded by local vancomycin powder.
Vancomycin powder also had an effect on the cells themselves, which Eder said included the fact the pseudopodes in cells exposed to the powder were fundamentally changed and this negatively affected their ability to migrate and contact neighboring cells, which is a prerequisite for tissue regeneration.
Cell properties changed
Eder and colleagues also looked at the pseudopode information, which cells use to migrate and contact neighboring cells and is a prerequisite of tissue regeneration.
“If you look at the control slide, you can see numerous pseudopodes from the cell touching a neighbor cell. The number of pseudopodes is smaller in the low-dose group than in the middle- and high-dose group. Looking at the high-dose group, we only have some remnant of pseudopodes, but most of the cells around it can lose the ability to attach and lose the ability to reach a neighbor cell and are free-floating in the cell culture medium,” Eder said.
After observing the effect of vancomycin powder in the low-dose, medium-dose and high-dose cultures, it is almost definite vancomycin interferes with the parameters tested that influence bone fusion after spine surgery, according to Eder. – by Robert Linnehan
Reference:
Eder C, et al. Paper #70. Presented at: EuroSpine Annual Meeting; Oct. 1-3, 2014; Lyon, France.
For more information:
Claudia Eder, MD, can be reached at Orthopädische Abteilung, Orthopädisches Spital Speising, Speisinger Str. 109, 1130, Vienna, Austria; email: claudia.eder@oss.at.
Disclosure: Eder reports she received a grant from DePuy Synthes paid directly to the employer/institution.
Perspective
Back to TopVancomycin powder has been suggested as a powerful tool to reduce surgical site infection (SSI). Topical antibiotics have long been used in orthopedic trauma surgery to sterilize wounds and reduce the likelihood of infection. There have been a host of comparative retrospective and prospective studies supporting that vancomycin powder reduces the incidence of SSI.
In this interesting study, investigators performed an in-vitro analysis of cell viability and activity at specific doses of vancomycin on human bone tissue. With increased doses of vancomycin, there was a marked decrease in osteoblast migration, proliferation and viability. These results suggest that topical vancomycin may inhibit spine fusion.
Kristen E. Radcliff
An increased rate of pseudoarthrosis has not been observed in the clinical studies describing usage of topical vancomycin powder. Secondary markers of pseudoarthrosis, such as worse clinical outcome, also have not been reported. Additionally, topical antibiotics are often used in orthopedic trauma and arthroplasty applications without significant effects on bone healing.
Vancomycin powder has promise to significantly increase the safety of open spine surgery. Prospective, randomized studies (NCT01566422, NCT01977989 and NCT01764750) that are now underway will help definitively answer questions about the optimal dosage, delivery mode, site and adverse effects.
References:
Radcliff KE, et al. Spine J. 2015;doi:10.1016/j.spinee.2014.09.022
Sweet FA, et al. Spine. 2011;doi:10.1097/BRS.0b013e3181ff2cb1.
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