Progress not panacea: vancomycin powder efficacy and dose evaluated in an in vivo mouse model of spine implant infection
Intrawound vancomycin powder (VP) has been rapidly adopted in spine surgery with apparent benefit demonstrated in limited, retrospective studies. Randomized trials, basic science, and dose response studies are scarce. This study aims to test the efficacy and dose effect of VP over an extended time c...
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| Veröffentlicht in: | The spine journal 2020-06, Vol.20 (6), p.973-980 |
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| creator | Park, Howard Y. Hegde, Vishal Zoller, Stephen D. Sheppard, William Hamad, Christopher Smith, Ryan A. Sprague, Marina M. Proal, Joshua D. Hoang, John Loftin, Amanda Blumstein, Gideon Burke, Zachary Cevallos, Nicolas Scaduto, Anthony A. Bernthal, Nicholas M. |
| description | Intrawound vancomycin powder (VP) has been rapidly adopted in spine surgery with apparent benefit demonstrated in limited, retrospective studies. Randomized trials, basic science, and dose response studies are scarce.
This study aims to test the efficacy and dose effect of VP over an extended time course within a randomized, controlled in vivo animal experiment.
Randomized controlled experiment utilizing a mouse model of spine implant infection with treatment groups receiving vancomycin powder following bacterial inoculation.
Utilizing a mouse model of spine implant infection with bioluminescent Staphylococcus aureus, 24 mice were randomized into 3 groups: 10 infected mice with VP treatment (+VP), 10 infected mice without VP treatment (No-VP), and 4 sterile controls (SC). Four milligrams of VP (mouse equivalent of 1 g in a human) were administered before wound closure. Bioluminescence imaging was performed over 5 weeks to quantify bacterial burden. Electron microscopy (EM), bacterial colonization assays (Live/Dead) staining, and colony forming units (CFU) analyses were completed. A second dosing experiment was completed with 34 mice randomized into 4 groups: control, 2 mg, 4 mg, and 8 mg groups.
The (+VP) treatment group exhibited significantly lower bacterial loads compared to the control (No-VP) group, (p |
| doi_str_mv | 10.1016/j.spinee.2019.12.007 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7351246</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1529943019311453</els_id><sourcerecordid>2329734407</sourcerecordid><originalsourceid>FETCH-LOGICAL-c463t-8627aff2ba7fb36a629a0291fc36ac2991948bd77cb8e43e61658c82e891f2773</originalsourceid><addsrcrecordid>eNp9UctuFDEQtBCIJAt_gJCPXGbwY9YPDkgoAoIUCQ5wtjyedvBqxh7s2Qn793izIcCFix_q6q6qLoReUNJSQsXrXVvmEAFaRqhuKWsJkY_QOVVSNVRw9ri-t0w3uuPkDF2UsiOEKEnZU3TGqRJcc3aOfn7J6SZDKTimBc82Wgf2DV5tdGk6uBDxnG4HyBi8D866A7ZxwEMqgGG1494uMOCKsvF4rmFNeEr7Wp3SACNOHt-pxGGaRxuXCvLglpDiM_TE27HA8_t7g759eP_18qq5_vzx0-W768Z1gi-NEkxa71lvpe-5sIJpS5im3tWPY1pT3al-kNL1CjoOgoqtcoqBqhgmJd-gt6e5876fYHAQl2xHM-cw2XwwyQbzbyWG7-YmrUbyLWVVwwa9uh-Q0489lMVMoTgYqx2oTg3jTEvedeTI1Z2gLqdSMvgHGkrMMTSzM6fQzDE0Q5khd20v_5b40PQ7pT8eoC5qDZBNcQGigyHkuk0zpPB_hl8E260z</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2329734407</pqid></control><display><type>article</type><title>Progress not panacea: vancomycin powder efficacy and dose evaluated in an in vivo mouse model of spine implant infection</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Park, Howard Y. ; Hegde, Vishal ; Zoller, Stephen D. ; Sheppard, William ; Hamad, Christopher ; Smith, Ryan A. ; Sprague, Marina M. ; Proal, Joshua D. ; Hoang, John ; Loftin, Amanda ; Blumstein, Gideon ; Burke, Zachary ; Cevallos, Nicolas ; Scaduto, Anthony A. ; Bernthal, Nicholas M.</creator><creatorcontrib>Park, Howard Y. ; Hegde, Vishal ; Zoller, Stephen D. ; Sheppard, William ; Hamad, Christopher ; Smith, Ryan A. ; Sprague, Marina M. ; Proal, Joshua D. ; Hoang, John ; Loftin, Amanda ; Blumstein, Gideon ; Burke, Zachary ; Cevallos, Nicolas ; Scaduto, Anthony A. ; Bernthal, Nicholas M.</creatorcontrib><description>Intrawound vancomycin powder (VP) has been rapidly adopted in spine surgery with apparent benefit demonstrated in limited, retrospective studies. Randomized trials, basic science, and dose response studies are scarce.
This study aims to test the efficacy and dose effect of VP over an extended time course within a randomized, controlled in vivo animal experiment.
Randomized controlled experiment utilizing a mouse model of spine implant infection with treatment groups receiving vancomycin powder following bacterial inoculation.
Utilizing a mouse model of spine implant infection with bioluminescent Staphylococcus aureus, 24 mice were randomized into 3 groups: 10 infected mice with VP treatment (+VP), 10 infected mice without VP treatment (No-VP), and 4 sterile controls (SC). Four milligrams of VP (mouse equivalent of 1 g in a human) were administered before wound closure. Bioluminescence imaging was performed over 5 weeks to quantify bacterial burden. Electron microscopy (EM), bacterial colonization assays (Live/Dead) staining, and colony forming units (CFU) analyses were completed. A second dosing experiment was completed with 34 mice randomized into 4 groups: control, 2 mg, 4 mg, and 8 mg groups.
The (+VP) treatment group exhibited significantly lower bacterial loads compared to the control (No-VP) group, (p<.001). CFU analysis at the conclusion of the experiment revealed 20% of mice in the +VP group and 67% of mice in the No-VP group had persistent infections, and the (+VP) treatment group had significantly less mean number of CFUs (p<.03). EM and Live/Dead staining revealed florid biofilm formation in the No-VP group. Bioluminescence was suppressed in all VP doses tested compared with sterile controls (p<.001). CFU analysis revealed a 40%, 10%, and 20% persistent infection rate in the 2 mg, 4 mg, and 8 mg dose groups, respectively. CFU counts across dosing groups were not statistically different (p=.56).
Vancomycin powder provided an overall infection prevention benefit but failed to eradicate infection in all mice. Furthermore, the dose when halved also demonstrated an overall protective benefit, albeit at a lower rate.
Vancomycin powder is efficacious but should not be viewed as a panacea for perioperative infection prevention. Dose alterations can be considered, especially in patients with kidney disease or at high risk for seroma.</description><identifier>ISSN: 1529-9430</identifier><identifier>EISSN: 1878-1632</identifier><identifier>DOI: 10.1016/j.spinee.2019.12.007</identifier><identifier>PMID: 31863932</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Anti-Bacterial Agents - therapeutic use ; Biofilm ; Infection ; Mice ; Powders ; Retrospective Studies ; Surgical site infection ; Surgical Wound Infection - drug therapy ; Vancomycin - therapeutic use ; Vancomycin powder</subject><ispartof>The spine journal, 2020-06, Vol.20 (6), p.973-980</ispartof><rights>2019</rights><rights>Copyright © 2019. Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-8627aff2ba7fb36a629a0291fc36ac2991948bd77cb8e43e61658c82e891f2773</citedby><cites>FETCH-LOGICAL-c463t-8627aff2ba7fb36a629a0291fc36ac2991948bd77cb8e43e61658c82e891f2773</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.spinee.2019.12.007$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31863932$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Howard Y.</creatorcontrib><creatorcontrib>Hegde, Vishal</creatorcontrib><creatorcontrib>Zoller, Stephen D.</creatorcontrib><creatorcontrib>Sheppard, William</creatorcontrib><creatorcontrib>Hamad, Christopher</creatorcontrib><creatorcontrib>Smith, Ryan A.</creatorcontrib><creatorcontrib>Sprague, Marina M.</creatorcontrib><creatorcontrib>Proal, Joshua D.</creatorcontrib><creatorcontrib>Hoang, John</creatorcontrib><creatorcontrib>Loftin, Amanda</creatorcontrib><creatorcontrib>Blumstein, Gideon</creatorcontrib><creatorcontrib>Burke, Zachary</creatorcontrib><creatorcontrib>Cevallos, Nicolas</creatorcontrib><creatorcontrib>Scaduto, Anthony A.</creatorcontrib><creatorcontrib>Bernthal, Nicholas M.</creatorcontrib><title>Progress not panacea: vancomycin powder efficacy and dose evaluated in an in vivo mouse model of spine implant infection</title><title>The spine journal</title><addtitle>Spine J</addtitle><description>Intrawound vancomycin powder (VP) has been rapidly adopted in spine surgery with apparent benefit demonstrated in limited, retrospective studies. Randomized trials, basic science, and dose response studies are scarce.
This study aims to test the efficacy and dose effect of VP over an extended time course within a randomized, controlled in vivo animal experiment.
Randomized controlled experiment utilizing a mouse model of spine implant infection with treatment groups receiving vancomycin powder following bacterial inoculation.
Utilizing a mouse model of spine implant infection with bioluminescent Staphylococcus aureus, 24 mice were randomized into 3 groups: 10 infected mice with VP treatment (+VP), 10 infected mice without VP treatment (No-VP), and 4 sterile controls (SC). Four milligrams of VP (mouse equivalent of 1 g in a human) were administered before wound closure. Bioluminescence imaging was performed over 5 weeks to quantify bacterial burden. Electron microscopy (EM), bacterial colonization assays (Live/Dead) staining, and colony forming units (CFU) analyses were completed. A second dosing experiment was completed with 34 mice randomized into 4 groups: control, 2 mg, 4 mg, and 8 mg groups.
The (+VP) treatment group exhibited significantly lower bacterial loads compared to the control (No-VP) group, (p<.001). CFU analysis at the conclusion of the experiment revealed 20% of mice in the +VP group and 67% of mice in the No-VP group had persistent infections, and the (+VP) treatment group had significantly less mean number of CFUs (p<.03). EM and Live/Dead staining revealed florid biofilm formation in the No-VP group. Bioluminescence was suppressed in all VP doses tested compared with sterile controls (p<.001). CFU analysis revealed a 40%, 10%, and 20% persistent infection rate in the 2 mg, 4 mg, and 8 mg dose groups, respectively. CFU counts across dosing groups were not statistically different (p=.56).
Vancomycin powder provided an overall infection prevention benefit but failed to eradicate infection in all mice. Furthermore, the dose when halved also demonstrated an overall protective benefit, albeit at a lower rate.
Vancomycin powder is efficacious but should not be viewed as a panacea for perioperative infection prevention. Dose alterations can be considered, especially in patients with kidney disease or at high risk for seroma.</description><subject>Animals</subject><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>Biofilm</subject><subject>Infection</subject><subject>Mice</subject><subject>Powders</subject><subject>Retrospective Studies</subject><subject>Surgical site infection</subject><subject>Surgical Wound Infection - drug therapy</subject><subject>Vancomycin - therapeutic use</subject><subject>Vancomycin powder</subject><issn>1529-9430</issn><issn>1878-1632</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UctuFDEQtBCIJAt_gJCPXGbwY9YPDkgoAoIUCQ5wtjyedvBqxh7s2Qn793izIcCFix_q6q6qLoReUNJSQsXrXVvmEAFaRqhuKWsJkY_QOVVSNVRw9ri-t0w3uuPkDF2UsiOEKEnZU3TGqRJcc3aOfn7J6SZDKTimBc82Wgf2DV5tdGk6uBDxnG4HyBi8D866A7ZxwEMqgGG1494uMOCKsvF4rmFNeEr7Wp3SACNOHt-pxGGaRxuXCvLglpDiM_TE27HA8_t7g759eP_18qq5_vzx0-W768Z1gi-NEkxa71lvpe-5sIJpS5im3tWPY1pT3al-kNL1CjoOgoqtcoqBqhgmJd-gt6e5876fYHAQl2xHM-cw2XwwyQbzbyWG7-YmrUbyLWVVwwa9uh-Q0489lMVMoTgYqx2oTg3jTEvedeTI1Z2gLqdSMvgHGkrMMTSzM6fQzDE0Q5khd20v_5b40PQ7pT8eoC5qDZBNcQGigyHkuk0zpPB_hl8E260z</recordid><startdate>20200601</startdate><enddate>20200601</enddate><creator>Park, Howard Y.</creator><creator>Hegde, Vishal</creator><creator>Zoller, Stephen D.</creator><creator>Sheppard, William</creator><creator>Hamad, Christopher</creator><creator>Smith, Ryan A.</creator><creator>Sprague, Marina M.</creator><creator>Proal, Joshua D.</creator><creator>Hoang, John</creator><creator>Loftin, Amanda</creator><creator>Blumstein, Gideon</creator><creator>Burke, Zachary</creator><creator>Cevallos, Nicolas</creator><creator>Scaduto, Anthony A.</creator><creator>Bernthal, Nicholas M.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200601</creationdate><title>Progress not panacea: vancomycin powder efficacy and dose evaluated in an in vivo mouse model of spine implant infection</title><author>Park, Howard Y. ; Hegde, Vishal ; Zoller, Stephen D. ; Sheppard, William ; Hamad, Christopher ; Smith, Ryan A. ; Sprague, Marina M. ; Proal, Joshua D. ; Hoang, John ; Loftin, Amanda ; Blumstein, Gideon ; Burke, Zachary ; Cevallos, Nicolas ; Scaduto, Anthony A. ; Bernthal, Nicholas M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-8627aff2ba7fb36a629a0291fc36ac2991948bd77cb8e43e61658c82e891f2773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Anti-Bacterial Agents - therapeutic use</topic><topic>Biofilm</topic><topic>Infection</topic><topic>Mice</topic><topic>Powders</topic><topic>Retrospective Studies</topic><topic>Surgical site infection</topic><topic>Surgical Wound Infection - drug therapy</topic><topic>Vancomycin - therapeutic use</topic><topic>Vancomycin powder</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Howard Y.</creatorcontrib><creatorcontrib>Hegde, Vishal</creatorcontrib><creatorcontrib>Zoller, Stephen D.</creatorcontrib><creatorcontrib>Sheppard, William</creatorcontrib><creatorcontrib>Hamad, Christopher</creatorcontrib><creatorcontrib>Smith, Ryan A.</creatorcontrib><creatorcontrib>Sprague, Marina M.</creatorcontrib><creatorcontrib>Proal, Joshua D.</creatorcontrib><creatorcontrib>Hoang, John</creatorcontrib><creatorcontrib>Loftin, Amanda</creatorcontrib><creatorcontrib>Blumstein, Gideon</creatorcontrib><creatorcontrib>Burke, Zachary</creatorcontrib><creatorcontrib>Cevallos, Nicolas</creatorcontrib><creatorcontrib>Scaduto, Anthony A.</creatorcontrib><creatorcontrib>Bernthal, Nicholas M.</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>The spine journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Howard Y.</au><au>Hegde, Vishal</au><au>Zoller, Stephen D.</au><au>Sheppard, William</au><au>Hamad, Christopher</au><au>Smith, Ryan A.</au><au>Sprague, Marina M.</au><au>Proal, Joshua D.</au><au>Hoang, John</au><au>Loftin, Amanda</au><au>Blumstein, Gideon</au><au>Burke, Zachary</au><au>Cevallos, Nicolas</au><au>Scaduto, Anthony A.</au><au>Bernthal, Nicholas M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Progress not panacea: vancomycin powder efficacy and dose evaluated in an in vivo mouse model of spine implant infection</atitle><jtitle>The spine journal</jtitle><addtitle>Spine J</addtitle><date>2020-06-01</date><risdate>2020</risdate><volume>20</volume><issue>6</issue><spage>973</spage><epage>980</epage><pages>973-980</pages><issn>1529-9430</issn><eissn>1878-1632</eissn><abstract>Intrawound vancomycin powder (VP) has been rapidly adopted in spine surgery with apparent benefit demonstrated in limited, retrospective studies. Randomized trials, basic science, and dose response studies are scarce.
This study aims to test the efficacy and dose effect of VP over an extended time course within a randomized, controlled in vivo animal experiment.
Randomized controlled experiment utilizing a mouse model of spine implant infection with treatment groups receiving vancomycin powder following bacterial inoculation.
Utilizing a mouse model of spine implant infection with bioluminescent Staphylococcus aureus, 24 mice were randomized into 3 groups: 10 infected mice with VP treatment (+VP), 10 infected mice without VP treatment (No-VP), and 4 sterile controls (SC). Four milligrams of VP (mouse equivalent of 1 g in a human) were administered before wound closure. Bioluminescence imaging was performed over 5 weeks to quantify bacterial burden. Electron microscopy (EM), bacterial colonization assays (Live/Dead) staining, and colony forming units (CFU) analyses were completed. A second dosing experiment was completed with 34 mice randomized into 4 groups: control, 2 mg, 4 mg, and 8 mg groups.
The (+VP) treatment group exhibited significantly lower bacterial loads compared to the control (No-VP) group, (p<.001). CFU analysis at the conclusion of the experiment revealed 20% of mice in the +VP group and 67% of mice in the No-VP group had persistent infections, and the (+VP) treatment group had significantly less mean number of CFUs (p<.03). EM and Live/Dead staining revealed florid biofilm formation in the No-VP group. Bioluminescence was suppressed in all VP doses tested compared with sterile controls (p<.001). CFU analysis revealed a 40%, 10%, and 20% persistent infection rate in the 2 mg, 4 mg, and 8 mg dose groups, respectively. CFU counts across dosing groups were not statistically different (p=.56).
Vancomycin powder provided an overall infection prevention benefit but failed to eradicate infection in all mice. Furthermore, the dose when halved also demonstrated an overall protective benefit, albeit at a lower rate.
Vancomycin powder is efficacious but should not be viewed as a panacea for perioperative infection prevention. Dose alterations can be considered, especially in patients with kidney disease or at high risk for seroma.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>31863932</pmid><doi>10.1016/j.spinee.2019.12.007</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Anti-Bacterial Agents - therapeutic use Biofilm Infection Mice Powders Retrospective Studies Surgical site infection Surgical Wound Infection - drug therapy Vancomycin - therapeutic use Vancomycin powder |
| title | Progress not panacea: vancomycin powder efficacy and dose evaluated in an in vivo mouse model of spine implant infection |
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