Local Intramedullary Delivery of Vancomycin Can Prevent the Development of Long Bone Staphylococcus aureus Infection
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 medu...
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description | 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. |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0160187</identifier><identifier>PMID: 27472197</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Anti-Bacterial Agents - administration & dosage ; Anti-Bacterial Agents - pharmacokinetics ; Antibiotics ; Antimicrobial agents ; Bacteria ; Biocompatibility ; Biology and Life Sciences ; Biomedical materials ; Blood plasma ; Bone and Bones ; Bones ; Chemotherapy ; Chromatography, High Pressure Liquid ; Complications and side effects ; Dosage and administration ; Drug Administration Routes ; Drug resistance ; Epidemiology ; Feasibility studies ; Health aspects ; Infections ; Inoculum ; Intravenous administration ; Long bone ; Low concentrations ; Male ; Medicine and Health Sciences ; Methicillin ; Methicillin-Resistant Staphylococcus aureus - isolation & purification ; Muscles ; Nosocomial infections ; Osteomyelitis ; Osteomyelitis - drug therapy ; Osteomyelitis - microbiology ; Pharmacokinetics ; Pharmacology ; Plastic surgery ; Prevention ; Rats ; Rats, Sprague-Dawley ; Research and Analysis Methods ; Risk factors ; Risk reduction ; Rodents ; Staphylococcus aureus ; Staphylococcus aureus infections ; Staphylococcus infections ; Tibia ; Toxicity ; Transplants & implants ; Vancomycin ; Vancomycin - administration & dosage ; Vancomycin - pharmacokinetics</subject><ispartof>PloS one, 2016-07, Vol.11 (7), p.e0160187</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication: https://creativecommons.org/publicdomain/zero/1.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c725t-313cf43ac73d36a95dd11a559dc0ddbcc815cca461ed8440786dbb3f9ae538573</citedby><cites>FETCH-LOGICAL-c725t-313cf43ac73d36a95dd11a559dc0ddbcc815cca461ed8440786dbb3f9ae538573</cites><orcidid>0000-0002-7265-1203</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966941/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966941/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23847,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27472197$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Chen, Chih-Jung</contributor><creatorcontrib>Loc-Carrillo, Catherine</creatorcontrib><creatorcontrib>Wang, Caroline</creatorcontrib><creatorcontrib>Canden, Ahranee</creatorcontrib><creatorcontrib>Burr, Michael</creatorcontrib><creatorcontrib>Agarwal, Jayant</creatorcontrib><title>Local Intramedullary Delivery of Vancomycin Can Prevent the Development of Long Bone Staphylococcus aureus Infection</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Current treatments for methicillin-resistant Staphylococcus aureus (MRSA) infections require intravenously delivered vancomycin; however, systemically delivered vancomycin has its problems. 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27472197</pmid><doi>10.1371/journal.pone.0160187</doi><tpages>e0160187</tpages><orcidid>https://orcid.org/0000-0002-7265-1203</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Animals Anti-Bacterial Agents - administration & dosage Anti-Bacterial Agents - pharmacokinetics Antibiotics Antimicrobial agents Bacteria Biocompatibility Biology and Life Sciences Biomedical materials Blood plasma Bone and Bones Bones Chemotherapy Chromatography, High Pressure Liquid Complications and side effects Dosage and administration Drug Administration Routes Drug resistance Epidemiology Feasibility studies Health aspects Infections Inoculum Intravenous administration Long bone Low concentrations Male Medicine and Health Sciences Methicillin Methicillin-Resistant Staphylococcus aureus - isolation & purification Muscles Nosocomial infections Osteomyelitis Osteomyelitis - drug therapy Osteomyelitis - microbiology Pharmacokinetics Pharmacology Plastic surgery Prevention Rats Rats, Sprague-Dawley Research and Analysis Methods Risk factors Risk reduction Rodents Staphylococcus aureus Staphylococcus aureus infections Staphylococcus infections Tibia Toxicity Transplants & implants Vancomycin Vancomycin - administration & dosage Vancomycin - pharmacokinetics |
title | Local Intramedullary Delivery of Vancomycin Can Prevent the Development of Long Bone Staphylococcus aureus Infection |
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