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

Background: 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 k...

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Main Authors: 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, Jodhbir Singh
Other Authors: Mohan, Rajiv R.
Format: Article
Language:English
Published: 2015
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Online Access:https://hdl.handle.net/10356/81216
http://hdl.handle.net/10220/39163
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-812162023-07-14T15:45:47Z Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis 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, Jodhbir Singh Mohan, Rajiv R. School of Materials Science & Engineering Eye infections Background: 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. Methodology: 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. Results: 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. Conclusions: 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. NRF (Natl Research Foundation, S’pore) Published version 2015-12-18T06:26:29Z 2019-12-06T14:23:51Z 2015-12-18T06:26:29Z 2019-12-06T14:23:51Z 2015 Journal Article Konstantopoulos, A., Tan, X. W., Goh, G. T. W., Saraswathi, P., Chen, L., Nyein, C. L., et al. (2015). Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis. PLoS ONE, 10(10), e0139653-. 1932-6203 https://hdl.handle.net/10356/81216 http://hdl.handle.net/10220/39163 10.1371/journal.pone.0139653 26460791 en PLoS ONE © 2015 Konstantopoulos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 13 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Eye infections
spellingShingle Eye infections
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, Jodhbir Singh
Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis
description Background: 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. Methodology: 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. Results: 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. Conclusions: 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.
author2 Mohan, Rajiv R.
author_facet Mohan, Rajiv R.
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, Jodhbir Singh
format Article
author 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, Jodhbir Singh
author_sort Konstantopoulos, Aris
title 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_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_sort prophylactic vancomycin drops reduce the severity of early bacterial keratitis in keratoprosthesis
publishDate 2015
url https://hdl.handle.net/10356/81216
http://hdl.handle.net/10220/39163
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