Topical Delivery of Ultrahigh Concentrations of Gentamicin Is Highly Effective in Reducing Bacterial Levels in Infected Porcine Full-Thickness Wounds
Injury to the skin can predispose individuals to invasive infection. The standard of care for infected wounds is treatment with intravenous antibiotics. However, antibiotics delivered intravenously may have poor tissue penetration and be dose limited by systemic side effects. Topical delivery of ant...
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Veröffentlicht in: | Plastic and reconstructive surgery (1963) 2015-01, Vol.135 (1), p.151-159 |
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container_title | Plastic and reconstructive surgery (1963) |
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creator | Junker, Johan P. E. Lee, Cameron C. Y. Samaan, Soleil Hackl, Florian Kiwanuka, Elizabeth Minasian, Raquel A. Tsai, David M. Tracy, Lauren E. Onderdonk, Andrew B. Eriksson, Elof Caterson, E. J. |
description | Injury to the skin can predispose individuals to invasive infection. The standard of care for infected wounds is treatment with intravenous antibiotics. However, antibiotics delivered intravenously may have poor tissue penetration and be dose limited by systemic side effects. Topical delivery of antibiotics reduces systemic complications and delivers increased drug concentrations directly to the wound.
Porcine full-thickness wounds infected with Staphylococcus aureus were treated with ultrahigh concentrations (over 1000 times the minimum inhibitory concentration) of gentamicin using an incubator-like wound healing platform. The aim of the present study was to evaluate clearance of infection and reduction in inflammation following treatment. Gentamicin cytotoxicity was evaluated by in vitro assays.
Application of 2000 μg/ml gentamicin decreased bacterial counts in wound tissue from 7.2 ± 0.3 log colony-forming units/g to 2.6 ± 0.6 log colony-forming units/g in 6 hours, with no reduction observed in saline controls (p < 0.005). Bacterial counts in wound fluid decreased from 5.7 ± 0.9 log colony-forming units/ml to 0.0 ± 0 log colony-forming units/ml in 1 hour, with no reduction observed in saline controls (p < 0.005). Levels of interleukin-1β were significantly reduced in gentamicin-treated wounds compared with saline controls (p < 0.005). In vitro, keratinocyte migration and proliferation were reduced at gentamicin concentrations between 100 and 1000 μg/ml.
Topical delivery of ultrahigh concentrations of gentamicin rapidly decontaminates acutely infected wounds and maintains safe systemic levels. Treatment of infected wounds using the proposed methodology protects the wound and establishes a favorable baseline for subsequent treatment. |
doi_str_mv | 10.1097/PRS.0000000000000801 |
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Porcine full-thickness wounds infected with Staphylococcus aureus were treated with ultrahigh concentrations (over 1000 times the minimum inhibitory concentration) of gentamicin using an incubator-like wound healing platform. The aim of the present study was to evaluate clearance of infection and reduction in inflammation following treatment. Gentamicin cytotoxicity was evaluated by in vitro assays.
Application of 2000 μg/ml gentamicin decreased bacterial counts in wound tissue from 7.2 ± 0.3 log colony-forming units/g to 2.6 ± 0.6 log colony-forming units/g in 6 hours, with no reduction observed in saline controls (p < 0.005). Bacterial counts in wound fluid decreased from 5.7 ± 0.9 log colony-forming units/ml to 0.0 ± 0 log colony-forming units/ml in 1 hour, with no reduction observed in saline controls (p < 0.005). Levels of interleukin-1β were significantly reduced in gentamicin-treated wounds compared with saline controls (p < 0.005). In vitro, keratinocyte migration and proliferation were reduced at gentamicin concentrations between 100 and 1000 μg/ml.
Topical delivery of ultrahigh concentrations of gentamicin rapidly decontaminates acutely infected wounds and maintains safe systemic levels. Treatment of infected wounds using the proposed methodology protects the wound and establishes a favorable baseline for subsequent treatment.</description><identifier>ISSN: 0032-1052</identifier><identifier>EISSN: 1529-4242</identifier><identifier>DOI: 10.1097/PRS.0000000000000801</identifier><identifier>PMID: 25539303</identifier><language>eng</language><publisher>United States: American Society of Plastic Surgeons</publisher><subject>Administration, Topical ; Animals ; Anti-Bacterial Agents - administration & dosage ; Female ; Gentamicins - administration & dosage ; Staphylococcal Infections - drug therapy ; Swine ; Wound Infection - drug therapy</subject><ispartof>Plastic and reconstructive surgery (1963), 2015-01, Vol.135 (1), p.151-159</ispartof><rights>American Society of Plastic Surgeons</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3520-71a36a907af903d3bd9adec0a6ff5ddb22785f552b2526cd8f95331596e7a80d3</citedby><cites>FETCH-LOGICAL-c3520-71a36a907af903d3bd9adec0a6ff5ddb22785f552b2526cd8f95331596e7a80d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25539303$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Junker, Johan P. E.</creatorcontrib><creatorcontrib>Lee, Cameron C. Y.</creatorcontrib><creatorcontrib>Samaan, Soleil</creatorcontrib><creatorcontrib>Hackl, Florian</creatorcontrib><creatorcontrib>Kiwanuka, Elizabeth</creatorcontrib><creatorcontrib>Minasian, Raquel A.</creatorcontrib><creatorcontrib>Tsai, David M.</creatorcontrib><creatorcontrib>Tracy, Lauren E.</creatorcontrib><creatorcontrib>Onderdonk, Andrew B.</creatorcontrib><creatorcontrib>Eriksson, Elof</creatorcontrib><creatorcontrib>Caterson, E. J.</creatorcontrib><title>Topical Delivery of Ultrahigh Concentrations of Gentamicin Is Highly Effective in Reducing Bacterial Levels in Infected Porcine Full-Thickness Wounds</title><title>Plastic and reconstructive surgery (1963)</title><addtitle>Plast Reconstr Surg</addtitle><description>Injury to the skin can predispose individuals to invasive infection. The standard of care for infected wounds is treatment with intravenous antibiotics. However, antibiotics delivered intravenously may have poor tissue penetration and be dose limited by systemic side effects. Topical delivery of antibiotics reduces systemic complications and delivers increased drug concentrations directly to the wound.
Porcine full-thickness wounds infected with Staphylococcus aureus were treated with ultrahigh concentrations (over 1000 times the minimum inhibitory concentration) of gentamicin using an incubator-like wound healing platform. The aim of the present study was to evaluate clearance of infection and reduction in inflammation following treatment. Gentamicin cytotoxicity was evaluated by in vitro assays.
Application of 2000 μg/ml gentamicin decreased bacterial counts in wound tissue from 7.2 ± 0.3 log colony-forming units/g to 2.6 ± 0.6 log colony-forming units/g in 6 hours, with no reduction observed in saline controls (p < 0.005). Bacterial counts in wound fluid decreased from 5.7 ± 0.9 log colony-forming units/ml to 0.0 ± 0 log colony-forming units/ml in 1 hour, with no reduction observed in saline controls (p < 0.005). Levels of interleukin-1β were significantly reduced in gentamicin-treated wounds compared with saline controls (p < 0.005). In vitro, keratinocyte migration and proliferation were reduced at gentamicin concentrations between 100 and 1000 μg/ml.
Topical delivery of ultrahigh concentrations of gentamicin rapidly decontaminates acutely infected wounds and maintains safe systemic levels. Treatment of infected wounds using the proposed methodology protects the wound and establishes a favorable baseline for subsequent treatment.</description><subject>Administration, Topical</subject><subject>Animals</subject><subject>Anti-Bacterial Agents - administration & dosage</subject><subject>Female</subject><subject>Gentamicins - administration & dosage</subject><subject>Staphylococcal Infections - drug therapy</subject><subject>Swine</subject><subject>Wound Infection - drug therapy</subject><issn>0032-1052</issn><issn>1529-4242</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdUdlqGzEUFaUlcdP8QSl67MukV9JolsfW2QyGhsShj4MsXWXUyCNXmknwh_R_KzfpQgQXce5ZBDqEvGdwwqCtP11d35zA_6cB9orMmORtUfKSvyYzAMELBpIfkrcpfQdgtajkATnkUopWgJiRn6uwdVp5eorePWDc0WDprR-j6t1dT-dh0DhkNLowpD13kaHaOO0Gukj0Mov8jp5Zi3rMfprX12imTN_RL0qPGF0OX-ID-rQnF8NeiYZehZhFSM8n74tV7_T9gCnRb2EaTHpH3ljlEx4_30fk9vxsNb8sll8vFvPPy0ILyaGomRKVaqFWtgVhxNq0yqAGVVkrjVlzXjfSSsnXXPJKm8a2Uggm2wpr1YARR-TjU-42hh8TprHbuKTRezVgmFLHqhKqpq04z9LySapjSCmi7bbRbVTcdQy6fSFdLqR7WUi2fXh-YVpv0Pw1_WngX-5j8Pm30r2fHjF2PSo_9r_zKinKggOTwDIq8mTfL7OOl4E</recordid><startdate>20150101</startdate><enddate>20150101</enddate><creator>Junker, Johan P. 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Y. ; Samaan, Soleil ; Hackl, Florian ; Kiwanuka, Elizabeth ; Minasian, Raquel A. ; Tsai, David M. ; Tracy, Lauren E. ; Onderdonk, Andrew B. ; Eriksson, Elof ; Caterson, E. J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3520-71a36a907af903d3bd9adec0a6ff5ddb22785f552b2526cd8f95331596e7a80d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Administration, Topical</topic><topic>Animals</topic><topic>Anti-Bacterial Agents - administration & dosage</topic><topic>Female</topic><topic>Gentamicins - administration & dosage</topic><topic>Staphylococcal Infections - drug therapy</topic><topic>Swine</topic><topic>Wound Infection - drug therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Junker, Johan P. E.</creatorcontrib><creatorcontrib>Lee, Cameron C. Y.</creatorcontrib><creatorcontrib>Samaan, Soleil</creatorcontrib><creatorcontrib>Hackl, Florian</creatorcontrib><creatorcontrib>Kiwanuka, Elizabeth</creatorcontrib><creatorcontrib>Minasian, Raquel A.</creatorcontrib><creatorcontrib>Tsai, David M.</creatorcontrib><creatorcontrib>Tracy, Lauren E.</creatorcontrib><creatorcontrib>Onderdonk, Andrew B.</creatorcontrib><creatorcontrib>Eriksson, Elof</creatorcontrib><creatorcontrib>Caterson, E. J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Plastic and reconstructive surgery (1963)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Junker, Johan P. E.</au><au>Lee, Cameron C. Y.</au><au>Samaan, Soleil</au><au>Hackl, Florian</au><au>Kiwanuka, Elizabeth</au><au>Minasian, Raquel A.</au><au>Tsai, David M.</au><au>Tracy, Lauren E.</au><au>Onderdonk, Andrew B.</au><au>Eriksson, Elof</au><au>Caterson, E. J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Topical Delivery of Ultrahigh Concentrations of Gentamicin Is Highly Effective in Reducing Bacterial Levels in Infected Porcine Full-Thickness Wounds</atitle><jtitle>Plastic and reconstructive surgery (1963)</jtitle><addtitle>Plast Reconstr Surg</addtitle><date>2015-01-01</date><risdate>2015</risdate><volume>135</volume><issue>1</issue><spage>151</spage><epage>159</epage><pages>151-159</pages><issn>0032-1052</issn><eissn>1529-4242</eissn><abstract>Injury to the skin can predispose individuals to invasive infection. The standard of care for infected wounds is treatment with intravenous antibiotics. However, antibiotics delivered intravenously may have poor tissue penetration and be dose limited by systemic side effects. Topical delivery of antibiotics reduces systemic complications and delivers increased drug concentrations directly to the wound.
Porcine full-thickness wounds infected with Staphylococcus aureus were treated with ultrahigh concentrations (over 1000 times the minimum inhibitory concentration) of gentamicin using an incubator-like wound healing platform. The aim of the present study was to evaluate clearance of infection and reduction in inflammation following treatment. Gentamicin cytotoxicity was evaluated by in vitro assays.
Application of 2000 μg/ml gentamicin decreased bacterial counts in wound tissue from 7.2 ± 0.3 log colony-forming units/g to 2.6 ± 0.6 log colony-forming units/g in 6 hours, with no reduction observed in saline controls (p < 0.005). Bacterial counts in wound fluid decreased from 5.7 ± 0.9 log colony-forming units/ml to 0.0 ± 0 log colony-forming units/ml in 1 hour, with no reduction observed in saline controls (p < 0.005). Levels of interleukin-1β were significantly reduced in gentamicin-treated wounds compared with saline controls (p < 0.005). In vitro, keratinocyte migration and proliferation were reduced at gentamicin concentrations between 100 and 1000 μg/ml.
Topical delivery of ultrahigh concentrations of gentamicin rapidly decontaminates acutely infected wounds and maintains safe systemic levels. Treatment of infected wounds using the proposed methodology protects the wound and establishes a favorable baseline for subsequent treatment.</abstract><cop>United States</cop><pub>American Society of Plastic Surgeons</pub><pmid>25539303</pmid><doi>10.1097/PRS.0000000000000801</doi><tpages>9</tpages></addata></record> |
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subjects | Administration, Topical Animals Anti-Bacterial Agents - administration & dosage Female Gentamicins - administration & dosage Staphylococcal Infections - drug therapy Swine Wound Infection - drug therapy |
title | Topical Delivery of Ultrahigh Concentrations of Gentamicin Is Highly Effective in Reducing Bacterial Levels in Infected Porcine Full-Thickness Wounds |
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