title: Local Intramedullary Delivery of Vancomycin Can Prevent the Development of Long Bone Staphylococcus aureus Infection.
abstract: Current treatments for methicillin-resistant Staphylococcus aureus (MRSA) infections require intravenously delivered vancomycin; however, systemically delivered vancomycin has its problems. To determine the feasibility and safety of locally delivering vancomycin hydrochloride (~25 mg/Kg) to the medullary canal of long bones, we conducted a pharmacokinetics study using a rat tibia model. We found that administering the vancomycin intraosseously resulted in very low concentrations of vancomycin in the blood plasma and the muscle surrounding the tibia, reducing the risk for systemic toxicity, which is often seen with traditional intravenous administration of vancomycin. Additionally, we were able to inhibit the development of osteomyelitis in the tibia if the treatment was administered locally at the same time as a bacterial inoculum (i.e., Log10 7.82 CFU/mL or 6.62x107 CFU/mL), when compared to an untreated group. These findings suggest that local intramedullary vancomycin delivery can achieve sufficiently high local concentrations to prevent development of osteomyelitis while minimizing systemic toxicity.
authors.affiliation: VA Salt Lake City Health Care System, Salt Lake City, Utah, United States of America.|Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
authors.forename: Catherine
authors.identifier: http://orcid.org/0000-0002-7265-1203
authors.initials: C
authors.lastname: Loc-Carrillo
authors.affiliation: VA Salt Lake City Health Care System, Salt Lake City, Utah, United States of America.
authors.forename: Caroline
authors.initials: C
authors.lastname: Wang
authors.affiliation: VA Salt Lake City Health Care System, Salt Lake City, Utah, United States of America.
authors.forename: Ahranee
authors.initials: A
authors.lastname: Canden
authors.affiliation: Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Burr
authors.affiliation: VA Salt Lake City Health Care System, Salt Lake City, Utah, United States of America.|Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
authors.forename: Jayant
authors.initials: J
authors.lastname: Agarwal
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001842:Bone and Bones; D002851:Chromatography, High Pressure Liquid; D004333:Drug Administration Routes; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000302:isolation & purification*; D010019:Osteomyelitis / Q000188:drug therapy* / Q000382:microbiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014640:Vancomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin