Title

Covalent Attachment of Antibiotics to Bone Allograft

Date of Award

2015

Degree Type

Thesis

Degree Name

Master of Science (MS)

First Advisor

Christopher Adams, PhD

Second Advisor

Denah Appelt, PhD

Third Advisor

Dawn Shell, PhD

Fourth Advisor

Marcus Bell, PhD

Abstract

The prevalence of joint replacement surgery is steadily rising, and rising with it is the risk of peri-prosthetic infection (PPI). PPI poses a significant risk to the patient and is a huge economic burden on the healthcare system. As the materials used in joint replacement can serve as a nidus of infection, we have pursued the strategy of tethering antibiotics to these materials in the hopes of creating an environment inhospitable to infectious organisms. The current study addresses the problem of creating broad-spectrum coverage on the surface of allograft bone for use in joint replacement. To achieve broad-spectrum coverage, we covalently tethered two antibiotics, vancomycin and tetracycline, to our model surface, morselized rat bone. The antibiotic-tethered bone was challenged by gram-positive S. aureus and gram-negative E. coli. Immunofluorescence indicated covalent tethering of vancomycin and tetracycline individually and in concert as a 50%vancomyin/50%tetracycline ratio. Colony counting and a bacterial LIVE/DEAD assay indicated that vancomycin-tethered morselized rat bone shows a trend towards the prevention of surface colonization of gram-positive S. aureus and to a lesser extent, gram-negative E. coli. Tetracycline-tethered bone and the combination of vancomycin and tetracycline tethered to bone showed significant reduction of surface colonization of both bacterial species. The morselized rat bone with a combination of antibiotics prevented nearly all colonization of S. aureus, the most prevalent causative organism of PPI. Clinically, the results of this study suggest an effective method of preventing bacterial colonization on an allograft bone surface, which could significantly reduce the risk of PPI following its surgical use.

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