Ocular Permeation of Topical Tazocin and Its Effectiveness in the Treatment of Pseudomonas aeruginosa Induced Keratitis in Rabbits

Purpose: Pseudomonas aeruginosa is the most common causative organism for contact lens-associated corneal ulcer and is commonly treated with fluoroquinolones. With the emergence of resistant strains, it is important to investigate alternative therapies. Despite well-established efficacy of tazocin a...

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Main Authors: Singh, Sujaya, Agarwal, Renu, Razak, Zulhilmi Abdul, Ngu, Robin, Nyein, Lwin L., Vasudevan, Sushil, Kapitonova, Marina, Kadir, Azida Juana, Subrayan, Visvaraja
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Published: Mary Ann Liebert 2018
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author Singh, Sujaya
Agarwal, Renu
Razak, Zulhilmi Abdul
Ngu, Robin
Nyein, Lwin L.
Vasudevan, Sushil
Kapitonova, Marina
Kadir, Azida Juana
Subrayan, Visvaraja
author_facet Singh, Sujaya
Agarwal, Renu
Razak, Zulhilmi Abdul
Ngu, Robin
Nyein, Lwin L.
Vasudevan, Sushil
Kapitonova, Marina
Kadir, Azida Juana
Subrayan, Visvaraja
author_sort Singh, Sujaya
collection UM
description Purpose: Pseudomonas aeruginosa is the most common causative organism for contact lens-associated corneal ulcer and is commonly treated with fluoroquinolones. With the emergence of resistant strains, it is important to investigate alternative therapies. Despite well-established efficacy of tazocin against systemic Pseudomonas infections, its topical use for the treatment of Pseudomonas keratitis has not been described, hence this study was aimed to find the ocular permeation of Tazocin and its efficacy in treating keratitis in rabbit eyes. Methods: We investigated the ocular permeation of topical tazocin after single drop application in normal rabbit eyes by estimating piperacillin and tazobactam concentrations in cornea, aqueous, and vitreous using a validated LC-MS/MS method. Furthermore, we determined the efficacy of repeated dose administration of tazocin against experimentally induced P. aeruginosa keratitis in rabbits in comparison to moxifloxacin. To determine the efficacy, clinical examination, histopathological examination, and estimation of bacterial load and inflammatory cytokines in cornea were done. Results: Significant corneal concentration of piperacillin and tazobactam was detected in normal rabbit corneas after single dose treatment with tazocin. In rabbits with Pseudomonas-induced keratitis, topical tazocin caused significant clinical and histopathological improvement. This improvement was associated with reduction in corneal bacterial load and inflammatory cytokines. Compared to moxifloxacin 0.5%, tazocin treated group showed greater clinical response which was associated with higher interleukin (IL)-1β, lower tumor necrosis factor (TNF)-α, a comparable level of IL-8, greater reduction in corneal bacterial load, and lesser inflammatory cell infiltration. Conclusion: Tazocin showed good ocular penetration and was effective in treatment of Pseudomonas induced keratitis in rabbits.
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spelling um.eprints-206492019-03-11T08:34:39Z http://eprints.um.edu.my/20649/ Ocular Permeation of Topical Tazocin and Its Effectiveness in the Treatment of Pseudomonas aeruginosa Induced Keratitis in Rabbits Singh, Sujaya Agarwal, Renu Razak, Zulhilmi Abdul Ngu, Robin Nyein, Lwin L. Vasudevan, Sushil Kapitonova, Marina Kadir, Azida Juana Subrayan, Visvaraja R Medicine Purpose: Pseudomonas aeruginosa is the most common causative organism for contact lens-associated corneal ulcer and is commonly treated with fluoroquinolones. With the emergence of resistant strains, it is important to investigate alternative therapies. Despite well-established efficacy of tazocin against systemic Pseudomonas infections, its topical use for the treatment of Pseudomonas keratitis has not been described, hence this study was aimed to find the ocular permeation of Tazocin and its efficacy in treating keratitis in rabbit eyes. Methods: We investigated the ocular permeation of topical tazocin after single drop application in normal rabbit eyes by estimating piperacillin and tazobactam concentrations in cornea, aqueous, and vitreous using a validated LC-MS/MS method. Furthermore, we determined the efficacy of repeated dose administration of tazocin against experimentally induced P. aeruginosa keratitis in rabbits in comparison to moxifloxacin. To determine the efficacy, clinical examination, histopathological examination, and estimation of bacterial load and inflammatory cytokines in cornea were done. Results: Significant corneal concentration of piperacillin and tazobactam was detected in normal rabbit corneas after single dose treatment with tazocin. In rabbits with Pseudomonas-induced keratitis, topical tazocin caused significant clinical and histopathological improvement. This improvement was associated with reduction in corneal bacterial load and inflammatory cytokines. Compared to moxifloxacin 0.5%, tazocin treated group showed greater clinical response which was associated with higher interleukin (IL)-1β, lower tumor necrosis factor (TNF)-α, a comparable level of IL-8, greater reduction in corneal bacterial load, and lesser inflammatory cell infiltration. Conclusion: Tazocin showed good ocular penetration and was effective in treatment of Pseudomonas induced keratitis in rabbits. Mary Ann Liebert 2018 Article PeerReviewed Singh, Sujaya and Agarwal, Renu and Razak, Zulhilmi Abdul and Ngu, Robin and Nyein, Lwin L. and Vasudevan, Sushil and Kapitonova, Marina and Kadir, Azida Juana and Subrayan, Visvaraja (2018) Ocular Permeation of Topical Tazocin and Its Effectiveness in the Treatment of Pseudomonas aeruginosa Induced Keratitis in Rabbits. Journal of Ocular Pharmacology and Therapeutics, 34 (1-2). pp. 214-223. ISSN 1080-7683, DOI https://doi.org/10.1089/jop.2017.0098 <https://doi.org/10.1089/jop.2017.0098>. https://doi.org/10.1089/jop.2017.0098 doi:10.1089/jop.2017.0098
spellingShingle R Medicine
Singh, Sujaya
Agarwal, Renu
Razak, Zulhilmi Abdul
Ngu, Robin
Nyein, Lwin L.
Vasudevan, Sushil
Kapitonova, Marina
Kadir, Azida Juana
Subrayan, Visvaraja
Ocular Permeation of Topical Tazocin and Its Effectiveness in the Treatment of Pseudomonas aeruginosa Induced Keratitis in Rabbits
title Ocular Permeation of Topical Tazocin and Its Effectiveness in the Treatment of Pseudomonas aeruginosa Induced Keratitis in Rabbits
title_full Ocular Permeation of Topical Tazocin and Its Effectiveness in the Treatment of Pseudomonas aeruginosa Induced Keratitis in Rabbits
title_fullStr Ocular Permeation of Topical Tazocin and Its Effectiveness in the Treatment of Pseudomonas aeruginosa Induced Keratitis in Rabbits
title_full_unstemmed Ocular Permeation of Topical Tazocin and Its Effectiveness in the Treatment of Pseudomonas aeruginosa Induced Keratitis in Rabbits
title_short Ocular Permeation of Topical Tazocin and Its Effectiveness in the Treatment of Pseudomonas aeruginosa Induced Keratitis in Rabbits
title_sort ocular permeation of topical tazocin and its effectiveness in the treatment of pseudomonas aeruginosa induced keratitis in rabbits
topic R Medicine
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