Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis

Artificial cornea transplantation, keratoprosthesis, improves vision for patients at high risk of failure with human cadaveric cornea. However, post-operative infection can cause visual loss and implant extrusion in 3.2-17% of eyes. Long-term vancomycin drops are recommended following keratoprosthes...

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Veröffentlicht in:PloS one 2015-10, Vol.10 (10), p.e0139653-e0139653
Hauptverfasser: Konstantopoulos, Aris, Tan, Xiao Wei, Goh, Gwendoline Tze Wei, Saraswathi, Padmanabhan, Chen, Liyan, Nyein, Chan Lwin, Zhou, Lei, Beuerman, Roger, Tan, Donald Tiang Hwee, Mehta, Jod S, Mehta, Jod
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container_issue 10
container_start_page e0139653
container_title PloS one
container_volume 10
creator Konstantopoulos, Aris
Tan, Xiao Wei
Goh, Gwendoline Tze Wei
Saraswathi, Padmanabhan
Chen, Liyan
Nyein, Chan Lwin
Zhou, Lei
Beuerman, Roger
Tan, Donald Tiang Hwee
Mehta, Jod S
Mehta, Jod
description Artificial cornea transplantation, keratoprosthesis, improves vision for patients at high risk of failure with human cadaveric cornea. However, post-operative infection can cause visual loss and implant extrusion in 3.2-17% of eyes. Long-term vancomycin drops are recommended following keratoprosthesis to prevent bacterial keratitis. Evidence, though, in support of this practice is poor. We investigated whether prophylactic vancomycin drops prevented bacterial keratitis in an animal keratoprosthesis model. Twenty-three rabbits were assigned either to a prophylactic group (n = 13) that received vancomycin 1.4% drops 5 times/day from keratoprosthesis implantation to sacrifice, or a non-prophylactic group (n = 10) that received no drops. All rabbits had Staphylococcus aureus inoculation into the cornea at 7-12 days post-implantation and were sacrificed at predetermined time-points. Prophylactic and non-prophylactic groups were compared with slit-lamp photography (SLP), anterior segment optical coherence tomography (AS-OCT), and histology, immunohistochemistry and bacterial quantification of excised corneas. Corneal vancomycin pharmacokinetics were studied in 8 additional rabbits. On day 1 post-inoculation, the median SLP score and mean±SEM AS-OCT corneal thickness (CT) were greater in the non-prophylactic than the prophylactic group (11 vs. 1, p = 0.049 and 486.9±61.2 vs. 327.4±37.1 μm, p = 0.029 respectively). On days 2 and 4, SLP scores and CT were not significantly different. Immunohistochemistry showed a greater CD11b+ve/non-CD11b+ve cell ratio in the non-prophylactic group (1.45 vs. 0.71) on day 2. Bacterial counts were not significantly different between the two groups. Corneal vancomycin concentration (2.835±0.383 μg/ml) exceeded minimum inhibitory concentration (MIC) for Staphylococcus aureus only after 16 days of vancomycin drops. Two of 3 rabbits still developed infection despite bacterial inoculation after 16 days of prophylactic drops. Prophylactic vancomycin drops provided short-term benefit, but did not prevent infection. Achieving MIC in the cornea was not sufficient to prevent Staphylococcus aureus keratitis. Patients should continue to be counselled regarding the risk of infection following keratoprosthesis.
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However, post-operative infection can cause visual loss and implant extrusion in 3.2-17% of eyes. Long-term vancomycin drops are recommended following keratoprosthesis to prevent bacterial keratitis. Evidence, though, in support of this practice is poor. We investigated whether prophylactic vancomycin drops prevented bacterial keratitis in an animal keratoprosthesis model. Twenty-three rabbits were assigned either to a prophylactic group (n = 13) that received vancomycin 1.4% drops 5 times/day from keratoprosthesis implantation to sacrifice, or a non-prophylactic group (n = 10) that received no drops. All rabbits had Staphylococcus aureus inoculation into the cornea at 7-12 days post-implantation and were sacrificed at predetermined time-points. Prophylactic and non-prophylactic groups were compared with slit-lamp photography (SLP), anterior segment optical coherence tomography (AS-OCT), and histology, immunohistochemistry and bacterial quantification of excised corneas. Corneal vancomycin pharmacokinetics were studied in 8 additional rabbits. On day 1 post-inoculation, the median SLP score and mean±SEM AS-OCT corneal thickness (CT) were greater in the non-prophylactic than the prophylactic group (11 vs. 1, p = 0.049 and 486.9±61.2 vs. 327.4±37.1 μm, p = 0.029 respectively). On days 2 and 4, SLP scores and CT were not significantly different. Immunohistochemistry showed a greater CD11b+ve/non-CD11b+ve cell ratio in the non-prophylactic group (1.45 vs. 0.71) on day 2. Bacterial counts were not significantly different between the two groups. Corneal vancomycin concentration (2.835±0.383 μg/ml) exceeded minimum inhibitory concentration (MIC) for Staphylococcus aureus only after 16 days of vancomycin drops. Two of 3 rabbits still developed infection despite bacterial inoculation after 16 days of prophylactic drops. Prophylactic vancomycin drops provided short-term benefit, but did not prevent infection. Achieving MIC in the cornea was not sufficient to prevent Staphylococcus aureus keratitis. Patients should continue to be counselled regarding the risk of infection following keratoprosthesis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0139653</identifier><identifier>PMID: 26460791</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Animals ; Anterior Eye Segment - drug effects ; Anterior Eye Segment - microbiology ; Anterior Eye Segment - pathology ; Antibiotics ; Bacteria ; Bacterial infections ; Blindness ; Cadavers ; Care and treatment ; CD11b antigen ; Cornea ; Cornea - pathology ; Development and progression ; Extrusion ; Eye (anatomy) ; Eye Infections, Bacterial - drug therapy ; Eye Infections, Bacterial - microbiology ; Eye Infections, Bacterial - prevention &amp; control ; Eye, Artificial ; Glaucoma ; Health aspects ; Health risks ; Histology ; Immunohistochemistry ; Implantation ; Infections ; Inoculation ; Keratitis ; Keratitis - drug therapy ; Keratitis - microbiology ; Keratitis - prevention &amp; control ; Laboratories ; Massachusetts ; Medical care ; Microbial Sensitivity Tests ; Minimum inhibitory concentration ; Ophthalmic Solutions - pharmacokinetics ; Ophthalmic Solutions - pharmacology ; Ophthalmic Solutions - therapeutic use ; Optical Coherence Tomography ; Patient outcomes ; Patients ; Pharmacokinetics ; Pharmacology ; Photography ; Prevention ; Rabbits ; Slit Lamp ; Staphylococcus aureus ; Streptococcus infections ; Surgery ; Titanium ; Tomography ; Tomography, Optical Coherence ; Transplantation ; Vancomycin ; Vancomycin - pharmacokinetics ; Vancomycin - pharmacology ; Vancomycin - therapeutic use ; Visual impairment</subject><ispartof>PloS one, 2015-10, Vol.10 (10), p.e0139653-e0139653</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Konstantopoulos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Konstantopoulos et al 2015 Konstantopoulos et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-b555a7ba10d5da479905107ad6c58eab91f934eb3f884d8409805f1829f4e85d3</citedby><cites>FETCH-LOGICAL-c692t-b555a7ba10d5da479905107ad6c58eab91f934eb3f884d8409805f1829f4e85d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604170/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604170/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23871,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26460791$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Mohan, Rajiv R.</contributor><creatorcontrib>Konstantopoulos, Aris</creatorcontrib><creatorcontrib>Tan, Xiao Wei</creatorcontrib><creatorcontrib>Goh, Gwendoline Tze Wei</creatorcontrib><creatorcontrib>Saraswathi, Padmanabhan</creatorcontrib><creatorcontrib>Chen, Liyan</creatorcontrib><creatorcontrib>Nyein, Chan Lwin</creatorcontrib><creatorcontrib>Zhou, Lei</creatorcontrib><creatorcontrib>Beuerman, Roger</creatorcontrib><creatorcontrib>Tan, Donald Tiang Hwee</creatorcontrib><creatorcontrib>Mehta, Jod S</creatorcontrib><creatorcontrib>Mehta, Jod</creatorcontrib><title>Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Artificial cornea transplantation, keratoprosthesis, improves vision for patients at high risk of failure with human cadaveric cornea. However, post-operative infection can cause visual loss and implant extrusion in 3.2-17% of eyes. Long-term vancomycin drops are recommended following keratoprosthesis to prevent bacterial keratitis. Evidence, though, in support of this practice is poor. We investigated whether prophylactic vancomycin drops prevented bacterial keratitis in an animal keratoprosthesis model. Twenty-three rabbits were assigned either to a prophylactic group (n = 13) that received vancomycin 1.4% drops 5 times/day from keratoprosthesis implantation to sacrifice, or a non-prophylactic group (n = 10) that received no drops. All rabbits had Staphylococcus aureus inoculation into the cornea at 7-12 days post-implantation and were sacrificed at predetermined time-points. Prophylactic and non-prophylactic groups were compared with slit-lamp photography (SLP), anterior segment optical coherence tomography (AS-OCT), and histology, immunohistochemistry and bacterial quantification of excised corneas. Corneal vancomycin pharmacokinetics were studied in 8 additional rabbits. On day 1 post-inoculation, the median SLP score and mean±SEM AS-OCT corneal thickness (CT) were greater in the non-prophylactic than the prophylactic group (11 vs. 1, p = 0.049 and 486.9±61.2 vs. 327.4±37.1 μm, p = 0.029 respectively). On days 2 and 4, SLP scores and CT were not significantly different. Immunohistochemistry showed a greater CD11b+ve/non-CD11b+ve cell ratio in the non-prophylactic group (1.45 vs. 0.71) on day 2. Bacterial counts were not significantly different between the two groups. Corneal vancomycin concentration (2.835±0.383 μg/ml) exceeded minimum inhibitory concentration (MIC) for Staphylococcus aureus only after 16 days of vancomycin drops. Two of 3 rabbits still developed infection despite bacterial inoculation after 16 days of prophylactic drops. Prophylactic vancomycin drops provided short-term benefit, but did not prevent infection. Achieving MIC in the cornea was not sufficient to prevent Staphylococcus aureus keratitis. Patients should continue to be counselled regarding the risk of infection following keratoprosthesis.</description><subject>Analysis</subject><subject>Animals</subject><subject>Anterior Eye Segment - drug effects</subject><subject>Anterior Eye Segment - microbiology</subject><subject>Anterior Eye Segment - pathology</subject><subject>Antibiotics</subject><subject>Bacteria</subject><subject>Bacterial infections</subject><subject>Blindness</subject><subject>Cadavers</subject><subject>Care and treatment</subject><subject>CD11b antigen</subject><subject>Cornea</subject><subject>Cornea - pathology</subject><subject>Development and progression</subject><subject>Extrusion</subject><subject>Eye (anatomy)</subject><subject>Eye Infections, Bacterial - drug therapy</subject><subject>Eye Infections, Bacterial - microbiology</subject><subject>Eye Infections, Bacterial - prevention &amp; control</subject><subject>Eye, Artificial</subject><subject>Glaucoma</subject><subject>Health aspects</subject><subject>Health risks</subject><subject>Histology</subject><subject>Immunohistochemistry</subject><subject>Implantation</subject><subject>Infections</subject><subject>Inoculation</subject><subject>Keratitis</subject><subject>Keratitis - drug therapy</subject><subject>Keratitis - microbiology</subject><subject>Keratitis - prevention &amp; 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Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Konstantopoulos, Aris</au><au>Tan, Xiao Wei</au><au>Goh, Gwendoline Tze Wei</au><au>Saraswathi, Padmanabhan</au><au>Chen, Liyan</au><au>Nyein, Chan Lwin</au><au>Zhou, Lei</au><au>Beuerman, Roger</au><au>Tan, Donald Tiang Hwee</au><au>Mehta, Jod S</au><au>Mehta, Jod</au><au>Mohan, Rajiv R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-10-13</date><risdate>2015</risdate><volume>10</volume><issue>10</issue><spage>e0139653</spage><epage>e0139653</epage><pages>e0139653-e0139653</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Artificial cornea transplantation, keratoprosthesis, improves vision for patients at high risk of failure with human cadaveric cornea. However, post-operative infection can cause visual loss and implant extrusion in 3.2-17% of eyes. Long-term vancomycin drops are recommended following keratoprosthesis to prevent bacterial keratitis. Evidence, though, in support of this practice is poor. We investigated whether prophylactic vancomycin drops prevented bacterial keratitis in an animal keratoprosthesis model. Twenty-three rabbits were assigned either to a prophylactic group (n = 13) that received vancomycin 1.4% drops 5 times/day from keratoprosthesis implantation to sacrifice, or a non-prophylactic group (n = 10) that received no drops. All rabbits had Staphylococcus aureus inoculation into the cornea at 7-12 days post-implantation and were sacrificed at predetermined time-points. Prophylactic and non-prophylactic groups were compared with slit-lamp photography (SLP), anterior segment optical coherence tomography (AS-OCT), and histology, immunohistochemistry and bacterial quantification of excised corneas. Corneal vancomycin pharmacokinetics were studied in 8 additional rabbits. On day 1 post-inoculation, the median SLP score and mean±SEM AS-OCT corneal thickness (CT) were greater in the non-prophylactic than the prophylactic group (11 vs. 1, p = 0.049 and 486.9±61.2 vs. 327.4±37.1 μm, p = 0.029 respectively). On days 2 and 4, SLP scores and CT were not significantly different. Immunohistochemistry showed a greater CD11b+ve/non-CD11b+ve cell ratio in the non-prophylactic group (1.45 vs. 0.71) on day 2. Bacterial counts were not significantly different between the two groups. Corneal vancomycin concentration (2.835±0.383 μg/ml) exceeded minimum inhibitory concentration (MIC) for Staphylococcus aureus only after 16 days of vancomycin drops. Two of 3 rabbits still developed infection despite bacterial inoculation after 16 days of prophylactic drops. Prophylactic vancomycin drops provided short-term benefit, but did not prevent infection. Achieving MIC in the cornea was not sufficient to prevent Staphylococcus aureus keratitis. Patients should continue to be counselled regarding the risk of infection following keratoprosthesis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26460791</pmid><doi>10.1371/journal.pone.0139653</doi><oa>free_for_read</oa></addata></record>
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1932-6203
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source MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry
subjects Analysis
Animals
Anterior Eye Segment - drug effects
Anterior Eye Segment - microbiology
Anterior Eye Segment - pathology
Antibiotics
Bacteria
Bacterial infections
Blindness
Cadavers
Care and treatment
CD11b antigen
Cornea
Cornea - pathology
Development and progression
Extrusion
Eye (anatomy)
Eye Infections, Bacterial - drug therapy
Eye Infections, Bacterial - microbiology
Eye Infections, Bacterial - prevention & control
Eye, Artificial
Glaucoma
Health aspects
Health risks
Histology
Immunohistochemistry
Implantation
Infections
Inoculation
Keratitis
Keratitis - drug therapy
Keratitis - microbiology
Keratitis - prevention & control
Laboratories
Massachusetts
Medical care
Microbial Sensitivity Tests
Minimum inhibitory concentration
Ophthalmic Solutions - pharmacokinetics
Ophthalmic Solutions - pharmacology
Ophthalmic Solutions - therapeutic use
Optical Coherence Tomography
Patient outcomes
Patients
Pharmacokinetics
Pharmacology
Photography
Prevention
Rabbits
Slit Lamp
Staphylococcus aureus
Streptococcus infections
Surgery
Titanium
Tomography
Tomography, Optical Coherence
Transplantation
Vancomycin
Vancomycin - pharmacokinetics
Vancomycin - pharmacology
Vancomycin - therapeutic use
Visual impairment
title Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis
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