Comparison of intravitreal antifungal 100 μg voriconazole and 5 μg amphotericin B in experimental Aspergillus flavus endophthalmitis model in rabbits

  • Alia Arianti Department of Ophthalmology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Kirana Hospital, Jakarta, Indonesia
  • Rianto Setiabudy Department of Clinical Pharmacology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Anna Rozaliyani Department of Parasitology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Nurjati Chairani Siregar Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Made Susiyanti Department of Ophthalmology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Kirana Hospital, Jakarta, Indonesia
Keywords: amphotericin B, Aspergillus flavus, endophthalmitis, voriconazole
Abstract viewed: 84 times
PDF downloaded: 79 times
HTML downloaded: 6 times
EPUB downloaded: 45 times

Abstract

BACKGROUND Fungal endophthalmitis is a sight-threatening disease associated with high morbidity and Aspergillus sp. is the most common causes. Voriconazole (VCZ) and Amphotericin B (AmB) are the most used antifungal drugs, while head-to-head comparison for in vivo intravitreal efficacy is still unknown. This study was aimed to compare the efficacy of both agents against Aspergillus flavus

METHODS A randomized, masked, controlled-experimental study was conducted on 15 albino New Zealand white rabbits. Endophthalmitis was induced by intravitreal inoculation of Aspergillus flavus. Intravitreal injection was given 24 hours post-inoculation, the rabbits were divided into three groups; 100 μg/0.1 ml VCZ intravitreal injection, 5 μg/0.1 ml AmB, and control. Clinical evaluation of corneal opacity, aqueous cells and flare, and vitreous opacity using Yang’s method of quantification were performed at day 1, 3, 5, 7, and 10 after treatment. Mycology quantitative analysis and histopathological examination were performed at the final evaluation. 

RESULTS Clinical evaluation showed improvement of inflammation in the VCZ and AmB treatment groups (Δ score −2.1 [2.8] and −1.0 [3.2]) compared with the control group (Δ score 0.8 [3.1]). Although the VCZ group demonstrated a better clinical response with less inflammation and relatively intact retina structures in the histopathology result. Number of fungal colony was significantly less in AmB group (CFU/0.1 ml, p < 0.05). 

CONCLUSIONS Favorable clinical improvement was shown in VCZ group compared to AmB group. Intravitreal VCZ showed a better clinical response tendency for Aspergillus flavus-induced endophthalmitis in rabbits.

References

  1. Schwartz SG, Flynn HW Jr, Scott IU. Endophthalmitis: classification and current management. Expert Rev Ophthalmol. 2007;2(3):385-96. https://doi.org/10.1586/17469899.2.3.385

  2. American Academy of Ophthalmology. Endophthalmitis. Intraocular inflammation and uveitis. 2011-2012. Section 9 basic and clinical science course. San Francisco: American Academy of Ophthalmology. 2012.269-71 p.

  3. Chakrabarti A, Shivaprakash MR, Singh R, Tarai B, George VK, Fomda BA, et al. Fungal endophthalmitis: fourteen years' experience from a center in India. Retina. 2008;28(10):1400-7. https://doi.org/10.1097/IAE.0b013e318185e943

  4. Aziza Y, Kodrat E, Saharman YR, Setiabudy R, Susiyanti M, Sjamsoe S. Efficacy of intravitreal levofloxacin 0.5% ophthalmic solution in treating Pseudomonas aeruginosa endophthalmitis on a rabbit model. Asia Pac J Ophthalmol (Phila). 2013;2(3):199-205. https://doi.org/10.1097/APO.0b013e3182970cc9

  5. Narang S, Gupta A, Gupta V, Dogra MR, Ram J, Pandav SS, et al. Fungal endophthalmitis following cataract surgery: clinical presentation, microbiological spectrum, and outcome. Am J Ophthalmol. 2001;132(5):609-17. https://doi.org/10.1016/S0002-9394(01)01180-1

  6. Wykoff CC, Flynn HW Jr, Miller D, Scott IU, Alfonso EC. Exogenous fungal endophthalmitis: microbiology and clinical outcomes. Ophthalmology. 2008;115(9):1501-7. https://doi.org/10.1016/j.ophtha.2008.02.027

  7. Haddock LJ, Flynn HW Jr, Dubovy SR, Khurana RN, Egbert PR. Histopathologic correlation of Aspergillus endophthalmitis following uncomplicated cataract surgery. Clin Ophthalmol. 2012;6:1573-7. https://doi.org/10.2147/OPTH.S35386

  8. Hedayati MT, Pasqualotto AC, Warn PA, Bowyer P, Denning DW. Aspergillus flavus: human pathogen, allergen and mycotoxin producer. Microbiology. 2007;153(Pt 6):1677-92. https://doi.org/10.1099/mic.0.2007/007641-0

  9. Kernt M, Neubauer AS, De Kaspar HM, Kampik A. Intravitreal voriconazole: in vitro safety-profile for fungal endophthalmitis. Retina. 2009;29(3):362-70. https://doi.org/10.1097/IAE.0b013e31818d4b9b

  10. Manzouri B, Vafidis GC, Wyse RK. Pharmacotherapy of fungal eye infections. Expert Opin Pharmacother. 2001;2(11):1849-57. https://doi.org/10.1517/14656566.2.11.1849

  11. Gao H, Pennesi M, Shah K, Qiao X, Hariprasad SM, Mieler WF, et al. Safety of intravitreal voriconazole: electroretinographic and histopathologic studies. Trans Am Ophthalmol Soc. 2003;101:183-9.

  12. Hariprasad SM, Mieler WF, Lin TK, Sponsel WE, Graybill JR. Voriconazole in the treatment of fungal eye infections: a review of current literature. Br J Ophthalmol. 2008;92(7):871-8. https://doi.org/10.1136/bjo.2007.136515

  13. Xiang-Gen W, Li-Na Y, Meng X, Hao-Ran J. Anti-infectious activity of intravitreal injectable voriconazole microspheres on experimental rabbit fungal endophthalmitis caused by Aspergillus fumigatus. J Pharm Sci. 2011;100(5):1745-59. https://doi.org/10.1002/jps.22402

  14. National Committee for Clinical Laboratory Standards. 2004. Method for antifungal disk diffusion susceptibility testing of yeasts: NCCLS document M44-A [Internet]. USA: National Committee for Clinical Laboratory Standards [Cited 2015 Nov 10]. Available from: https://www.researchgate.net/file.PostFileLoader.html?id=59089756615e2719c01d792c&assetKey=AS%3A489575295524865%401493735254732

  15. The Association for Research in Vision and Ophthalmology (ARVO). Statement for the use of animal in ophthalmic and vision research [Internet]. USA: The Association for Research in Vision and Ophthalmology [Cited 2015 Dec 2]. Available from: https://www.arvo.org/About/policies/statement-for-the-use-ofanimals-in-ophthalmic-and-vision-research/#six

  16. Yang X, Dong XG, Liu AM, Sun SY, Xie LX, Wang SG. A pharmacodynamics study of an intravitreal amphotericin B drug delivery system for the treatment of experimental Aspergillus fumigatus endophthalmitis. Zhonghua Yan Ke Za Zhi. 2007;43(6):546-53.

  17. Lee SY, Ryu EH, Moon SK, Kim HJ, Woo SY, Cho MS, et al. The efficacy of intravitreal gatifloxacin in experimental S. epidermidis endophthalmitis. J Korean Ophthalmol Soc. 2008;49(4):651-60. https://doi.org/10.3341/jkos.2008.49.4.651

  18. Aliyeva SE, Ullmann AJ, Kottler UB, Frising M, Schwenn O. Histological examination of an eye with endogenous Aspergillus endophthalmitis treated with oral voriconazole: a case report. Graefes Arch Clin Exp Ophthalmol. 2004;242(10):887-91. https://doi.org/10.1007/s00417-004-0901-3

  19. Axelrod AJ, Peyman GA. Intravitreal amphotericin b treatment of experimental fungal endophthalmitis. Am J Ophthalmol. 1973;76(4):584-8. https://doi.org/10.1016/0002-9394(73)90754-X

  20. Coats ML, Peyman GA. Intravitreal corticosteroids in the treatment of exogenous fungal endophthalmitis. Retina. 1992;12(1):46-51. https://doi.org/10.1097/00006982-199212010-00010

  21. Rudramurthy SM, Chakrabarti A, Geertsen E, Mouton JW, Meis JF. In vitro activity of isavuconazole against 208 Aspergillus flavus isolates in comparison with 7 other antifungal agents: assessment according to the methodology of the European Committee on antimicrobial susceptibility testing. Diagn Microbiol Infect Dis. 2011;71(4):370-7. https://doi.org/10.1016/j.diagmicrobio.2011.08.006

  22. Cannon JP, Fiscella R, Pattharachayakul S, Garey KW, De Alba F, Piscitelli S, et al. Comparative toxicity and concentrations of intravitreal amphotericin B formulations in a rabbit model. Invest Ophthalmol Vis Sci. 2003;44(5):2112-7. https://doi.org/10.1167/iovs.02-1020

  23. Radhika M, Mithal K, Bawdekar A, Dave V, Jindal A, Relhan N, et al. Pharmacokinetics of intravitreal antibiotics in endophthalmitis. J Ophthalmic Inflamm Infect. 2014;4:22. https://doi.org/10.1186/s12348-014-0022-z

  24. Shen YC, Wang MY, Wang CY, Tsai TC, Tsai HY, Lee YF, et al. Clearance of intravitreal voriconazole. Invest Ophthalmol Vis Sci. 2007;48(5):2238-41. https://doi.org/10.1167/iovs.06-1362

  25. Clemons KV, Stevens DA. The contribution of animal models of aspergillosis to understanding pathogenesis, therapy and virulence. Med Mycol. 2005;43 Suppl 1:S101-10. https://doi.org/10.1080/13693780500051919

Published
2019-10-04
How to Cite
1.
Arianti A, Setiabudy R, Rozaliyani A, Siregar NC, Susiyanti M. Comparison of intravitreal antifungal 100 μg voriconazole and 5 μg amphotericin B in experimental <em>Aspergillus flavus</em&gt; endophthalmitis model in rabbits. Med J Indones [Internet]. 2019Oct.4 [cited 2019Oct.21];28(3):215-22. Available from: https://mji.ui.ac.id/journal/index.php/mji/article/view/1794
Section
Basic Medical Research