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

<h4>Background</h4>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 recom...

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Main Authors: Aris Konstantopoulos, Xiao Wei Tan, Gwendoline Tze Wei Goh, Padmanabhan Saraswathi, Liyan Chen, Chan Lwin Nyein, Lei Zhou, Roger Beuerman, Donald Tiang Hwee Tan, Jod S Mehta
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0139653&type=printable
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author Aris Konstantopoulos
Xiao Wei Tan
Gwendoline Tze Wei Goh
Padmanabhan Saraswathi
Liyan Chen
Chan Lwin Nyein
Lei Zhou
Roger Beuerman
Donald Tiang Hwee Tan
Jod S Mehta
author_facet Aris Konstantopoulos
Xiao Wei Tan
Gwendoline Tze Wei Goh
Padmanabhan Saraswathi
Liyan Chen
Chan Lwin Nyein
Lei Zhou
Roger Beuerman
Donald Tiang Hwee Tan
Jod S Mehta
author_sort Aris Konstantopoulos
collection DOAJ
description <h4>Background</h4>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.<h4>Methodology</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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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spelling doaj-art-8fef01f61c774ad0899d6a3d72b7a1b92025-08-20T03:11:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011010e013965310.1371/journal.pone.0139653Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis.Aris KonstantopoulosXiao Wei TanGwendoline Tze Wei GohPadmanabhan SaraswathiLiyan ChenChan Lwin NyeinLei ZhouRoger BeuermanDonald Tiang Hwee TanJod S Mehta<h4>Background</h4>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.<h4>Methodology</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0139653&type=printable
spellingShingle Aris Konstantopoulos
Xiao Wei Tan
Gwendoline Tze Wei Goh
Padmanabhan Saraswathi
Liyan Chen
Chan Lwin Nyein
Lei Zhou
Roger Beuerman
Donald Tiang Hwee Tan
Jod S Mehta
Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis.
PLoS ONE
title Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis.
title_full Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis.
title_fullStr Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis.
title_full_unstemmed Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis.
title_short Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis.
title_sort prophylactic vancomycin drops reduce the severity of early bacterial keratitis in keratoprosthesis
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0139653&type=printable
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