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Antifungal Therapy in Eye Infections: New Drugs, New Trends

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Recent Trends in Antifungal Agents and Antifungal Therapy

Abstract

Treatment of ocular fungal infections represents a challenge for the ophthalmic clinician. Although an increased number of fungal infections of the eye have been reported in the past few decades, in part, because of increased clinical awareness and improved laboratory techniques, it is not matched by availability of effective ocular antifungal drugs. In addition, the need for improved antifungal therapy is emphasized by the potentially poor clinical outcome in patients with severe ocular mycoses. For an adequate therapeutic response, besides correct drug choice, an effectively administration is necessary. Current treatment for systemic fungal infections is not always sufficiently effective for ocular mycoses. The slower research and development progress in antifungal therapy compared with antibacterial therapy stems from the fact that fungal cells, unlike bacteria, are eukaryotic, consequently any drug that is toxic to fungal cells could potentially exert similar effects on mammalian cells. There also has been less financial incentive for pharmaceutical companies to invest in the development of ocular antifungal agents. Despite certain therapeutic advances, the impact of the availability of new antifungal agents on ocular mycosis is unknown. This chapter presents information about the major antifungal drugs used in eye infections, their dosages, administration routes, side effects and overall effectiveness.

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References

  • Abad JC, Foster CS (1996) Fungal keratitis. Int Ophthalmol Clin 36(3):1–15

    Article  CAS  PubMed  Google Scholar 

  • Agarwal PK, Roy P, Das A, Banerjee A, Maity PK, Banerjee AR (2001) Efficacy of topical and systemic itraconazole as a broadspectrum antifungal agent in mycotic corneal ulcer. A preliminary study. Indian J Ophthalmol 49(3):173–176

    CAS  PubMed  Google Scholar 

  • Al-Badriyeh D, Neoh CF, Stewart K, Kong DC (2010) Clinical utility of voriconazole eye drops in ophthalmic fungal keratitis. Clin Ophthalmol 4:391–405

    PubMed  PubMed Central  Google Scholar 

  • Alfonso ECGA, Miller D (2011) Fungal keratitis. In: Krachmer JH, Mannis MJ, Holland EJ (eds) Cornea: fundamentals, diagnosis and management, 3rd edn. Mosby Elsevier, New York

    Google Scholar 

  • Anderson KL, Mitra S, Salouti R, Pham TA, Taylor HR (2004) Fungal keratitis caused by Paecilomyces lilacinus associated with a retained intracorneal hair. Cornea 23(5):516–521

    Article  PubMed  Google Scholar 

  • Arora R, Gupta D, Goyal J, Kaul R (2011) Voriconazole versus natamycin as primary treatment in fungal corneal ulcers. Clin Exp Ophthalmol 39:434–440

    Article  PubMed  Google Scholar 

  • Avunduk AM, Beuerman RW, Warnel ED, Kaufman HE, Greer D (2003) Comparison of efficacy of topical and oral fluconazole treatment in experimental Aspergillus keratitis. Curr Eye Res 26(2):113–117

    Article  PubMed  Google Scholar 

  • Axelrod AJ, Peyman GA, Apple DJ (1973) Toxicity of intravitreal injection of amphotericin B. Am J Ophthalmol 76(4):578–583

    Article  CAS  PubMed  Google Scholar 

  • Bachmann SP, VandeWalle K, Ramage G, Patterson TF, Wickes BL, Graybill JR, López-Ribot JL (2002) In vitro activity of caspofungin against Candida albicans biofilms. Antimicrob Agents Chemother 46(11):3591–3596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barasch A, Griffin AV (2008) Miconazole revisited: new evidence of antifungal efficacy from laboratory and clinical trials. Future Microbiol 3(3):265–269

    Article  CAS  PubMed  Google Scholar 

  • Behrens-Baumann W (ed) (1999) Mycosis of the eye and its Adnexa. Dev Ophthalmol. Basel, Karger. 32:I–X. doi:10.1159/000060776

  • Bernauer W, Allan BDS, Dart JKG (1998) Successful management of Aspergillus scleritis by medical and surgical treatment. Eye 12:311–316

    Article  PubMed  Google Scholar 

  • Betts RF, Nucci M, Talwar D, Gareca M, Queiroz-Telles F, Bedimo RJ, Herbrecht R, Ruiz-Palacios G, Young JA, Baddley JW, Strohmaier KM, Tucker KA, Taylor AF, Kartsonis NA, Caspofungin High-Dose Study Group (2009) A multicenter, double-blind trial of a high-dose caspofungin treatment regimen versus a standard caspofungin treatment regimen for adult patients with invasive candidiasis. Clin Infect Dis 48:1676–1684

    Article  CAS  PubMed  Google Scholar 

  • Bunya VY, Hammersmith KM, Rapuano CJ, Ayres BD, Cohen EJ (2007) Topical and oral voriconazole in the treatment of fungal keratitis. Am J Ophthalmol 143(1):151–153

    Article  CAS  PubMed  Google Scholar 

  • Christmas NJ, Smiddy WE (1996) Vitrectomy and systemic fluconazole for treatment of endogenous fungal endophthalmitis. Ophthalmic Surg Lasers 27(12):1012–1018

    CAS  PubMed  Google Scholar 

  • Clinical and Laboratory Standard Institute (2009) Method for antifungal disk diffusion susceptibility testing of yeasts; approved guideline, 2nd edn. M44-A2 Clinical and Laboratory Standards Institute, Wayne

    Google Scholar 

  • Clinical Laboratory Standard Institute (2010) Reference method for antifungal disk diffusion susceptibility testing of non-dermatophyte filamentous fungi; approved guideline. CLSI document M51-A Clinical and Laboratory Standards Institute, Villanova

    Google Scholar 

  • Clode AB, Davis JL, Salmon J, Michau TM, Gilger BC (2006) Evaluation of concentration of voriconazole in aqueous humor after topical and oral administration in horses. Am J Vet Res 67(2):296–301

    Article  CAS  PubMed  Google Scholar 

  • Coley KC, Crain JL (1997) Miconazole-induced fatal dysrhythmia. Pharmacotherapy 17(2):379–382

    CAS  PubMed  Google Scholar 

  • Cuenca-Estrella M, Gomez-Lopez A, Mellado E, Buitrago MJ, Monzon A, Rodriguez-Tudela JL (2006) Head-to-head comparison of the activities of currently available antifungal agents against 3,378 Spanish clinical isolates of yeasts and filamentous fungi. Antimicrob Agents Chemother 50(3):917–921

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Diekema DJ, Messer SA, Hollis RJ, Jones RN, Pfaller MA (2003) Activities of caspofungin, itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B against 448 recent clinical isolates of filamentous fungi. J Clin Microbiol 41(8):3623–3626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dupuis A, Tournier N, Le Moal G, Venisse N (2009) Preparation and stability of voriconazole eye drop solution. Antimicrob Agents Chemother 53(2):798–799

    Article  CAS  PubMed  Google Scholar 

  • Dursun D, Fernandez V, Miller D, Alfonso EC (2003) Advanced Fusarium keratitis progressing to endophthalmitis. Cornea 22(4):300–303

    Article  PubMed  Google Scholar 

  • Fiscella RG, Moshifar M, Messick CR, Pendland PL, Chandler JW, Viana M (1997) Polyhexamethylene biguanide (PHMB) in the treatment of experimental Fusarium keratomycosis. Cornea 16:447–449

    Article  CAS  PubMed  Google Scholar 

  • Fitzsimons R, Peters AL (1986) Miconazole and ketoconazole as a satisfactory first-line treatment for keratomycosis. Am J Ophthalmol 101(5):605–608

    Article  CAS  PubMed  Google Scholar 

  • FlorCruz NV, Evans JR (2015) Medical interventions for fungal keratitis. Cochrane Database Syst Rev 4. doi:10.1002/14651858.CD004241.pub4

  • Foster CS (1981) Miconazole therapy for keratomycosis. Am J Ophthalmol 91(5):622–629

    Article  CAS  PubMed  Google Scholar 

  • Foster CS, Stefanyszyn M (1979) Intraocular penetration of miconazole in rabbits. Arch Ophthalmol 97(9):1703–1706

    Article  CAS  PubMed  Google Scholar 

  • Foster CS, Lass JH, Moran-Wallace K, Giovanoni R (1981) Ocular toxicity of topical antifungal agents. Arch Ophthalmol 99(6):1081–1084

    Article  CAS  PubMed  Google Scholar 

  • Fothergill AW (2006) Miconazole: a historical perspective. Expert Rev Anti Infect Ther 4(2):171–175

    Article  CAS  PubMed  Google Scholar 

  • Freda R (2006) Use of oral voriconazole as adjunctive treatment of severe cornea fungal infection: case report. Arq Bras Oftalmol 69(3):431–434

    Article  PubMed  Google Scholar 

  • Friedberg ML, Pleyer U, Mondino BJ (1991) Device drug delivery to the eye. Collagen shields, iontophoresis and pumps. Ophthalmology 98:725–732

    Article  CAS  PubMed  Google Scholar 

  • Gallis HA, Drew RH, Pickard WW (1990) Amphotericin B: 30 years of clinical experience. Rev Infect Dis 12(2):308–329

    Article  CAS  PubMed  Google Scholar 

  • Gao H, Pennesi M, Shah K, Qiao X, Hariprasad SM, Mieler WF, Wu SM, Holz ER (2003) Safety of intravitreal voriconazole: electroretinographic and histopathologic studies. Trans Am Ophthalmol Soc 101:183–189

    PubMed  Google Scholar 

  • Garcia- Valenzuela E, Song CD (2005) Intracorneal injection of amphothericin B for recurrent fungal keratitis and endophthalmitis. Arch Ophthalmol 123(12):1721–1723

    Article  PubMed  Google Scholar 

  • Gauthier GM, Nork TM, Prince R, Andes D (2005) Subtherapeutic ocular penetration of caspofungin and associated treatment failure in Candida albicans endophthalmitis. Clin Infect Dis 41(3):e27–e28

    Article  CAS  PubMed  Google Scholar 

  • Giaconi JA, Marangon FB, Miller D, Alfonso EC (2006) Voriconazole and fungal keratitis: a report of two treatment failures. J Ocul Pharmacol Ther 22(6):437–439

    Article  CAS  PubMed  Google Scholar 

  • Goldblum D, Frueh BE, Zimmerli S, Böhnke M (2000) Treatment of postkeratitis Fusarium endophthalmitis with amphotericin B lipid complex. Cornea 19(6):853–856

    Article  CAS  PubMed  Google Scholar 

  • Goldblum D, Frueh BE, Sarra GM, Katsoulis K, Zimmerli S (2005) Topical caspofungin for treatment of keratitis caused by Candida albicans in a rabbit model. Antimicrob Agents Chemother 49(4):1359–1363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Green WR, Bennett JE, Goos RD (1965) Ocular penetration of amphotericin B: a report of laboratory studies and a case report of postsurgical Cephalosporium endophthalmitis. Arch Ophthalmol 73:769–775

    Article  CAS  PubMed  Google Scholar 

  • Groll AH, Mickiene D, Petraitiene R, Petraitis V, Lyman CA, Bacher JS, Piscitelli SC, Walsh TJ (2001a) Pharmacokinetic and pharmacodynamic modeling of anidulafungin (LY303366): reappraisal of its efficacy in neutropenic animal models of opportunistic mycoses using optimal plasma sampling. Antimicrob Agents Chemother 45:2845–2855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Groll AH, Mickiene D, Petraitis V, Petraitiene R, Ibrahim KH, Piscitelli SC, Bekersky I, Walsh TJ (2001b) Compartmental pharmacokinetics and tissue distribution of the antifungal echinocandin lipopeptide micafungin (FK463) in rabbits. Antimicrob Agents Chemother 45:3322–3327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hariprasad SM, Mieler WF, Lin TK, Sponsel WE, Graybill JR (2008) Voriconazole in the treatment of fungal eye infections: a review of current literature. Br J Ophthalmol 92(7):871–878

    Article  CAS  PubMed  Google Scholar 

  • Heel RC, Brogden RN, Speight TM, Avery GS (1978) Econazole: a review of its antifungal activity and therapeutic efficacy. Drugs 16(3):177–201

    Article  CAS  PubMed  Google Scholar 

  • Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, Kern WV, Marr KA, Ribaud P, Lortholary O, Sylvester R, Rubin RH, Wingard JR, Stark P, Durand C, Caillot D, Thiel E, Chandrasekar PH, Hodges MR, Schlamm HT, Troke PF, de Pauw B, Invasive Fungal Infections Group of the European Organisation for Research and Treatment of Cancer and the Global Aspergillus Study Group (2002) Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 347(6):408–415

    Google Scholar 

  • Hirose H, Terasaki H, Awaya S, Yasuma T (1997) Treatment of fungal corneal ulcers with amphotericin B ointment. Am J Ophthalmol 124(6):836–838

    Article  CAS  PubMed  Google Scholar 

  • Ishibashi Y (1983) Oral ketoconazole therapy for keratomycosis. Am J Ophthalmol 95(3):342–345

    Article  CAS  PubMed  Google Scholar 

  • Ishibashi Y (1986) Miconazole and ketoconazole as a satisfactory first-line treatment for keratomycosis. Am J Ophthalmol 102(4):547–548

    Article  CAS  PubMed  Google Scholar 

  • Ishibashi Y, Kaufman HE (1985) The effects of subconjunctival miconazole in the treatment of experimental Candida keratitis in rabbits. Arch Ophthalmol 103(10):1570–1573

    Article  CAS  PubMed  Google Scholar 

  • Jang GJ, Kim KS, Shin WS, Lee WK (2005) Treatment of Candida chorioretinitis with voriconazole. Korean J Ophthalmol 19:73–76

    Article  PubMed  Google Scholar 

  • Johns KJ, O’Day DM (1988) Pharmacologic management of keratomycoses. Surv Ophthalmol 33:178–188

    Article  CAS  PubMed  Google Scholar 

  • Johnson LB, Kauffman CA (2003) Voriconazole: a new triazole antifungal agent. Clin Infect Dis 36(5):630–637

    Article  CAS  PubMed  Google Scholar 

  • Jones D (2004) Diagnosis and management of fungal keratitis. In: Tasman W, Jaeger EA (eds) Duane’s clinical ophthalmology. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  • Jones DB, Sexton R, Rebell G (1970) Mycotic keratitis in South Florida: a review of thirty-nine cases. Trans Ophthalmol Soc 89:781–797

    CAS  Google Scholar 

  • Jones DB, Forster FK, Rebell G (1972) Fusarium solani keratitis treated with natamycin (pimaricin): eighteen consecutive cases. Arch Ophthalmol 88(2):147–154

    Article  CAS  PubMed  Google Scholar 

  • Kalavathy CM, Parmar P, Kaliamurthy J, Philip VR, Ramalingam MD, Jesudasan CA, Thomas PA (2005) Comparison of topical itraconazole 1% with topical natamycin 5% for the treatment of filamentous fungal keratitis. Cornea 24(4):449–452

    Article  CAS  PubMed  Google Scholar 

  • Katz J, Khatry SK, Thapa MD, Schein OD, Kimbrough Pradhan E, LeClerq SC, West KP (2004) A randomised trial of povidone-iodine to reduce visual impairment from corneal ulcers in rural Nepal. Br J Ophthalmol 88(12):1487–1492

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaur IP, Rana C, Singh H (2008) Development of effective ocular preparations of antifungal agents. J Ocul Pharmacol Ther 24(5):481–493

    Article  CAS  PubMed  Google Scholar 

  • Kaushik S, Ram J, Brar GS, Jain AK, Chakraborti A, Gupta A (2001) Intracameral amphotericin B: initial experience in severe keratomycosis. Cornea 20(7):715–719

    Article  CAS  PubMed  Google Scholar 

  • Kermani NK, Aggarwal SP (2000) Isolated post-operative Aspergillus niger endophthalmitis. Eye (Lond). 14:114–116

    Google Scholar 

  • Khoo SH, Bond J, Denning DW (1994) Administering amphotericin B-a practical approach. J Antimicrob Chemother 33(2):203–213

    Article  CAS  PubMed  Google Scholar 

  • Klotz SA, Zahid M, Bartholomew WR, Revera PM, Butrus S (1996) Candida albicans keratitis treated successfully with itraconazole. Cornea 15(1):102–104

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi D, Kondo K, Uehara N, Otokozawa S, Tsuji N, Yagihashi A, Watanabe N (2002) Endogenous reactive oxygen species is an important mediator of miconazole antifungal effect. Antimicrob Agents Chemother 46(10):3113–3117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Komadina TG, Wilkes TD, Shock JP, Ulmer WC, Jackson J, Bradsher RW (1985) Treatment of Aspergillus fumigatus keratitis in rabbits with oral and topical ketoconazole. Am J Ophthalmol 99(4):476–479

    Article  CAS  PubMed  Google Scholar 

  • Kuriakose T, Kothari M, Paul P, Jacob P, Thomas R (2002) Intracameral amphotericin B injection in the management of deep keratomycosis. Cornea 21(7):653–656

    Article  PubMed  Google Scholar 

  • Kuse ER, Chetchotisakd P, da Cunha CA, Ruhnke M, Barrios C, Raghunadharao D, Sekhon JS, Freire A, Ramasubramanian V, Demeyer I, Nucci M, Leelarasamee A, Jacobs F, Decruyenaere J, Pittet D, Ullmann AJ, Ostrosky-Zeichner L, Lortholary O, Koblinger S, Diekmann-Berndt H, Cornely OA, Micafungin Invasive Candidiasis Working Group (2007) Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet 369:1519–1527

    Article  CAS  PubMed  Google Scholar 

  • Lalitha P, Shapiro BL, Srinivasan M, Prajna NV, Acharya NR, Fothergill AW, Ruiz J, Chidambaram JD, Maxey KJ, Hong KC, McLeod SD, Lietman TM (2007) Antimicrobial susceptibility of Fusarium, Aspergillus, and other filamentous fungi isolated from keratitis. Arch Ophthalmol 125(6):789–793

    Article  CAS  PubMed  Google Scholar 

  • Lalitha P, Vijaykumar R, Prajna NV, Fothergill AW (2008) In vitro natamycin susceptibility of ocular isolates of Fusarium and Aspergillus species: comparison of commercially formulated natamycin eye drops to pharmaceutical-grade powder. J Clin Microbiol 46:3477–3478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lalitha P, Prajna NV, Oldenburg CE, Srinivasan M, Krishnan T, Mascarenhas J, Vaitilingam CM, McLeod SD, Zegans ME, Porco TC, Acharya NR, Lietman TM (2012) Organism, minimum inhibitory concentration, and outcome in a fungal corneal ulcer clinical trial. Cornea 31:662–667

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee SJ, Lee JJ, Kim SD (2009) Topical and oral voriconazole in the treatment of fungal keratitis. Korean J Ophthalmol 23(1):46–48

    Article  PubMed  PubMed Central  Google Scholar 

  • Levin LA, Avery R, Shore JW, Woog JJ, Baker AS (1996) The spectrum of orbital aspergillosis: clinicopathological review. Surv Ophthalmol 41:142–154

    Article  CAS  PubMed  Google Scholar 

  • Li L, Wang Z, Li R, Luo S, Sun X (2008) In vitro evaluation of combination antifungal activity against Fusarium species isolated from ocular tissues of keratomycosis patients. Am J Ophthalmol 146:724–728

    Article  CAS  PubMed  Google Scholar 

  • Louie A, Liu W, Miller DA, Sucke AC, Liu QF, Drusano GL, Mayers M, Miller MH (1999) Efficacies of high-dose fluconazole plus amphotericin B and high-dose fluconazole plus 5-fluorocytosine versus amphotericin B, fluconazole, and 5-fluorocytosine monotherapies in treatment of experimental endocarditis, endophthalmitis, and pyelonephritis due to Candida albicans. Antimicrob Agents Chemother 43:2831–2840

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mahashabde S, Nahata MC, Shrivastava U (1987) A comparative study of anti-fungal drugs in mycotic corneal ulcer. Indian J Ophthalmol 35(5–6):149–152

    CAS  PubMed  Google Scholar 

  • Mahdy RA, Nada WM, Wageh MM, Kader MA, Saleh MM, Alswad MM (2010a) Assessment safety and efficacy of a combination therapy of topical amphotericin B and subconjunctival fluconazole for the treatment of fungal keratitis. Cutan Ocul Toxicol 29(3):193–197

    Article  CAS  PubMed  Google Scholar 

  • Mahdy RA, Nada WM, Wageh MM (2010b) Topical amphotericin B and subconjunctival injection of fluconazole (combination therapy) versus topical amphotericin B (monotherapy) in treatment of keratomycosis. J Ocul Pharmacol Ther 26(3):281–285

    Article  CAS  PubMed  Google Scholar 

  • Manzouri B, Vafidis GC, Wyse RK (2001) Pharmacotherapy of fungal eye infections. Expert Opin Pharmacother 2:1849–1857

    Article  CAS  PubMed  Google Scholar 

  • Marangon FB, Miller D, Giaconi JA, Alfonso EC (2004) In vitro investigation of voriconazole susceptibility for keratitis and endophthalmitis fungal pathogens. Am J Ophthalmol 137(5):820–825

    Article  CAS  PubMed  Google Scholar 

  • Matsumoto Y, Dogru M, Goto E, Fujishima H, Tsubota K (2005) Successful topical application of a new antifungal agent, micafungin, in the treatment of refractory fungal corneal ulcers: report of three cases and literature review. Cornea 24(6):748–753

    Article  PubMed  Google Scholar 

  • Matsumoto Y, Murat D, Kojima T, Shimazaki J, Tsubota K (2011) The comparison of solitary topical micafungin or fluconazole application in the treatment of Candida fungal keratitis. Br J Ophthalmol 95(10):1406–1409

    Article  PubMed  Google Scholar 

  • Mithal K, Pathengay A, Bawdekar A, Jindal A, Vira D, Relhan N, Choudhury H, Gupta N, Gupta V, Koday NK, Flynn HW Jr (2015) Filamentous fungal endophthalmitis: results of combination therapy with intravitreal amphotericin B and voriconazole. Clin Ophthalmol 9:649–655

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mohan M, Gupta SK, Kalra VK, Vajpayee RB, Sachdev MS (1987) Silver sulphadiazine in the treatment of mycotic keratitis. Indian J Med Res 85:572–575

    CAS  PubMed  Google Scholar 

  • Mohan M, Gupta SK, Kalra VK, Vajpayee RB, Sachdev MS (1988) Topical silver sulphadiazine: a new drug for ocular keratomycosis. Br J Ophthalmol 72:192–195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mohan M, Panda A, Gupta SK (1989) Management of human keratomycosis with miconazole. Aust N Z J Ophthalmol 17(3):295–297

    Article  CAS  PubMed  Google Scholar 

  • Mora-Duarte J, Betts R, Rotstein C, Colombo AL, Thompson-Moya L, Smietana J, Lupinacci R, Sable C, Kartsonis N, Perfect J, Caspofungin Invasive Candidiasis Study Group (2002) Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med 347(25):2020–2029

    Article  CAS  PubMed  Google Scholar 

  • Morris MI, Villmann M (2006a) Echinocandins in the management of invasive fungal infections, part 1. Am J Health Syst Pharm 63(18):1693–1703

    Article  CAS  PubMed  Google Scholar 

  • Morris MI, Villmann M (2006b) Echinocandins in the management of invasive fungal infections, part 2. Am J Health Syst Pharm 63(19):1813–1820

    Article  CAS  PubMed  Google Scholar 

  • Motukupally SR, Nanapur VR, Chathoth KN, Murthy SI, Pappuru RR, Mallick A, Sharma S (2015) Ocular infections caused by Candida species: type of species, in vitro susceptibility and treatment outcome. Indian J Med Microbiol 33(4):538–546

    Article  CAS  PubMed  Google Scholar 

  • Müller GG, Kara-José N, Castro RS (2013) Antifungals in eye infections: drugs and routes of administration. Revista Brasileira de Oftalmologia 72(2):132–141

    Article  Google Scholar 

  • Nulens E, Eggink C, Rijs AJ, Wesseling P, Verweij PE (2003) Keratitis caused by Scedosporium apiospermum successfully treated with a cornea transplant and voriconazole. J Clin Microbiol 41(5):2261–2264

    Article  PubMed  PubMed Central  Google Scholar 

  • O’Brien TP (1999) Therapy of ocular fungal infections. Ophthalmol Clin North Am 12:33–50

    Article  Google Scholar 

  • O’Day DM (1987) Selection of appropriate antifungal therapy. Cornea 6(4):238–245

    Article  PubMed  Google Scholar 

  • O’Day DM, Ray WA, Head WS, Robinson RD (1984) Influence of the corneal epithelium on the efficacy of topical antifungal agents. Invest Ophthalmol Vis Sci 25(7):855–859

    PubMed  Google Scholar 

  • O’Day DM, Head WS, Robinson RD, Stern WH, Freeman JM (1985) Intraocular penetration of systemically administered antifungal agents. Curr Eye Res 4(2):131–134

    Article  PubMed  Google Scholar 

  • O’Day DM, Head WS, Robinson RD, Clanton JA (1986) Corneal penetration of topical amphotericin B and natamycin. Curr Eye Res 5(11):877–882

    Article  PubMed  Google Scholar 

  • O’Day DM, Foulds G, Williams TE, Robinson RD, Allen RH, Head WS (1990) Ocular uptake of fluconazole following oral administration. Arch Ophthalmol 108(7):1006–1008

    Article  PubMed  Google Scholar 

  • O’Day DM, Ray WA, Robinson RD, Head WS, Williams TE (1991) Differences in response in vivo to amphotericin B among Candida albicans strains. Invest Ophthalmol Vis Sci 32(5):1569–1572

    PubMed  Google Scholar 

  • Odds FC, van Gerven F, Espinel-Ingroff A, Bartlett MS, Ghannoum MA, Lancaster MV, Pfaller MA, Rex JH, Rinaldi MG, Walsh TJ (1998) Evaluation of possible correlations between antifungal susceptibilities of filamentous fungi in vitro and antifungal treatment outcomes in animal infection models. Antimicrob Agents Chemother 42:282–288

    CAS  PubMed  PubMed Central  Google Scholar 

  • Oliveira PR, Resende SM, Oliveira FC, Oliveira AC (2001) Ceratite fúngica. Arq Bras Oftalmol 64(1):75–79

    Article  Google Scholar 

  • Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, Filler SG, Fisher JF, Kullberg BJ, Ostrosky-Zeichner L, Reboli AC, Rex JH, Walsh TJ, Sobel JD, Infectious Diseases Society of America (2009) Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 48:503–535

    Article  CAS  PubMed  Google Scholar 

  • Parchand S, Gupta A, Ram J, Gupta N, Chakrabarty A (2012) Voriconazole for fungal corneal ulcers. Ophthalmology 119(5):1083

    Article  PubMed  Google Scholar 

  • Pearce JW, Giuliano EA, Moore CP (2009) In vitro susceptibility patterns of Aspergillus and Fusarium species isolated from equine ulcerative keratomycosis cases in the midwestern and southern United States with inclusion of the new antifungal agent voriconazole. Vet Ophthalmol 12(5):318–324

    Article  CAS  PubMed  Google Scholar 

  • Polack FM, Kaufman HE, Newmark E (1971) Keratomycosis. Medical and surgical treatment. Arch Ophthalmol 85(4):410–416

    Article  CAS  PubMed  Google Scholar 

  • Pradhan L, Sharma S, Nalamada S, Sahu SK, Das S, Garg P (2011) Natamycin in the treatment of keratomycosis: correlation of treatment outcome and in vitro susceptibility of fungal isolates. Indian J Ophthalmol 59:512–514

    Article  PubMed  PubMed Central  Google Scholar 

  • Prajna NV, John RK, Nirmalan PK, Lalitha P, Srinivasan M (2003) A randomised clinical trial comparing 2% econazole and 5% natamycin for the treatment of fungal keratitis. Br J Ophthalmol 87(10):1235–1237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prajna NV, Nirmalan PK, Mahalakshmi R, Lalitha P, Srinivasan M (2004) Concurrent use of 5% natamycin and 2% econazole for the management of fungal keratitis. Cornea 23(8):793–796

    Article  PubMed  Google Scholar 

  • Prajna NV, Mascarenhas J, Krishnan T, Reddy PR, Prajna L, Srinivasan M, Vaitilingam CM, Hong KC, Lee SM, McLeod SD, Zegans ME, Porco TC, Lietman TM, Acharya NR (2010) Comparison of natamycin and voriconazole for the treatment of fungal keratitis. Arch Ophthalmol 128(6):672–678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prajna NV, Krishnan T, Mascarenhas J, Rajaraman R, Prajna L, Srinivasan M, Raghavan A, Oldenburg CE, Ray KJ, Zegans ME, McLeod SD, Porco TC, Acharya NR, Lietman TM, Mycotic Ulcer Treatment Trial Group. (2013) The mycotic ulcer treatment trial: a randomized trial comparing natamycin vs voriconazole. JAMA Ophthalmol 131(4):422–429

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Prakash G, Sharma N, Goel M, Titiyal JS, Vajpayee RB (2008) Evaluation of intrastromal injection of voriconazole as a therapeutic adjunctive for the management of deep recalcitrant fungal keratitis. Am J Ophthalmol 146(1):56–59

    Article  PubMed  Google Scholar 

  • Qiu WY, Yao YF, Zhu YF (2005) Fungal spectrum identified by a new slide culture and in vitro drug susceptibility using E test in fungal keratitis. Curr Eye Res 30:1113–1120

    Article  CAS  PubMed  Google Scholar 

  • Qu L, Li L, Xie H (2010) Corneal and aqueous humor concentrations of amphotericin B using three different routes of administration in a rabbit model. Ophthalmic Res 43(3):153–158

    Article  PubMed  Google Scholar 

  • Rahman MR, Minassian DC, Srinivasan M, Martin MJ, Johnson GJ (1997) Trial of chlorhexidine gluconate for fungal corneal ulcers. Ophthal Epidemiol 4(3):141–149

    Article  CAS  Google Scholar 

  • Rahman MR, Johnson GJ, Husain R, Howlader SA, Minassian DC (1998) Randomised trial of 0.2% chlorhexidine gluconate and 2.5% natamycin for fungal keratitis in Bangladesh. Br J Ophthalmol 82(8):919–925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rajasekaran J, Thomas PA, Kalavathy CM, Joseph PC, Abraham DJ (1987) Itraconazole therapy for fungal keratitis. Indian J Ophthalmol 35(5–6):157–160

    CAS  PubMed  Google Scholar 

  • Reboli AC, Rotstein C, Pappas PG, Chapman SW, Kett DH, Kumar D, Betts R, Wible M, Goldstein BP, Schranz J, Krause DS, Walsh TJ, Anidulafungin Study Group (2007) Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med 356:2472–2482

    Article  CAS  PubMed  Google Scholar 

  • Reddy PR, Reddy PS, Reddy AR, Saboo NK (1982) A comparative evaluation of Nystatin, Amphotericin-B and Miconazole in keratomycosis. Indian J Ophthalmol 30(4):249–250

    CAS  PubMed  Google Scholar 

  • Rex J, Pfaller M (2002) Has antifungal susceptibility testing come of age? Clin Infect Dis 35:982–989

    Article  CAS  PubMed  Google Scholar 

  • Riddell J IV, Comer GM, Kauffman CA (2011) Reviews of anti-infective agents: treatment of endogenous fungal endophthalmitis: focus on new antifungal agents. Clin Infect Dis 52(5):648–653

    Article  CAS  PubMed  Google Scholar 

  • Rosa RH Jr, Miller D, Alfonso EC (1994) The changing spectrum of fungal keratitis in south Florida. Ophthalmology 101:1005–1013

    Article  PubMed  Google Scholar 

  • Sawyer PR, Brogden RN, Pinder RM, Speight TM, Avery GS (1975) Miconazole: a review of its antifungal activity and therapeutic efficacy. Drugs 9(6):406–423

    Article  CAS  PubMed  Google Scholar 

  • Seiff SR, Choo PH, Carter SR (1999) Role of local amphotericin B therapy for sino-orbital fungal infections. Ophthalmic Plast Reconstr Surg 15:28–31

    Article  CAS  Google Scholar 

  • Serracarbassa PD, Peyman GA, Liang C, Calixto N Jr, Nair MG (1998) Toxicity and efficacy of intravitreal injection of spartanamicin B in the treatment of Candida endophthalmitis. Int Ophthalmol 22(1):53–58

    Article  CAS  PubMed  Google Scholar 

  • Sharma N, Agarwal P, Sinha R, Titiyal JS, Velpandian T, Vajpayee RB (2011) Evaluation of intrastromal voriconazole injection in recalcitrant deep fungal keratitis: case series. Br J Ophthalmol 95(12):1735–1737

    Article  PubMed  Google Scholar 

  • Sharma N, Chacko J, Velpandian T, Titiyal JS, Sinha R, Satpathy G, Tandon R, Vajpayee RB (2013) Comparative evaluation of topical versus intrastromal voriconazole as an adjunct to natamycin in recalcitrant fungal keratitis. Ophthalmology 120(4):677–681

    Article  PubMed  Google Scholar 

  • Sharma N, Sankaran P, Agarwal T, Arora T, Chawla B, Titiyal JS, Tandon R, Satapathy G, Vajpayee RB (2015) Evaluation of intracameral amphotericin B in the management of fungal keratitis: randomized controlled trial. Ocul Immunol Inflamm 23:1–5

    Article  Google Scholar 

  • Sharma S, Das S, Virdi A, Fernandes M, Sahu SK, Kumar Koday N, Ali MH, Garg P, Motukupally SR (2015) Re-appraisal of topical 1% voriconazole and 5% natamycin in the treatment of fungal keratitis in a randomised trial. Br J Ophthalmol 99(9):1190–1195

    Article  PubMed  Google Scholar 

  • Shirley SF, Little JR (1979a) Immunopotentiating effects of amphotericin B. I. Enhanced contact sensitivity in mice. J Immunol 123(6):2878–2882

    CAS  PubMed  Google Scholar 

  • Shirley SF, Little JR (1979b) Immunopotentiating effects of amphotericin B. II. Enhanced in vitro proliferative responses of murine lymphocytes. J Immunol 123(6):2883–2889

    CAS  PubMed  Google Scholar 

  • Siatiri H, Daneshgar F, Siatiri N, Khodabande A (2011) The effects of intrastromal voriconazole injection and topical voriconazole in the treatment of recalcitrant Fusarium keratitis. Cornea 30(8):872–875

    Article  PubMed  Google Scholar 

  • Singh SM, Khan R, Sharma S, Chatterjee PK (1989) Clinical and experimental mycotic corneal ulcer caused by Aspergillus fumigatus and the effect of oral ketoconazole in the treatment. Mycopathologia 106(3):133–141

    Article  CAS  PubMed  Google Scholar 

  • Souri EN, Green WR (1974) Intravitreal amphotericin B toxicity. Am J Ophthalmol 78(1):77–81

    Article  CAS  PubMed  Google Scholar 

  • Sponsel WE, Graybill JR, Nevarez HL, Dang D (2002) Ocular and systemic posaconazole(SCH-56592) treatment of invasive Fusarium solani keratitis and endophthalmitis. Br J Ophthalmol 86(7):829–830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Srinivasan M, Gonzales CA, George C (1997) Epidemiology and aetiological diagnosis of corneal ulceration in Madurai, South India. Br J Ophthalmol 81:965–971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sud IJ, Feingold DS (1981) Mechanisms of action of the antimycotic imidazoles. J Invest Dermatol 76(6):438–441

    Article  CAS  PubMed  Google Scholar 

  • Sullivan LJ, Snibson G, Joseph C, Taylor HR (1994) Scedosporium prolificans sclerokeratitis. Aust N Z J Ophthalmol 22:207–209

    Article  CAS  PubMed  Google Scholar 

  • Sun CQ, Prajna NV, Krishnan T, Mascarenhas J, Rajaraman R, Srinivasan M et al (2010) Expert prior elicitation and Bayesian analysis of the Mycotic Ulcer Treatment Trial I. Investig Ophthalmol Vis Sci 54(6):4167–4173

    Article  Google Scholar 

  • Sweetman S (2004) Martindale: the complete drug reference, 34th edn. Pharmaceutical Press, London, pp 550–554

    Google Scholar 

  • Thakar M (1994) Oral fluconazole therapy for keratomycosis. Acta Ophthalmol 72(6):765–767

    Article  CAS  Google Scholar 

  • Thevissen K, Ayscough KR, Aerts AM, Du W, De Brucker K, Meert EM, Ausma J, Borgers M, Cammue BP, François IE (2007) Miconazole induces changes in actin cytoskeleton prior to reactive oxygen species induction in yeast. J Biol Chem 282(30):21592–21597

    Article  CAS  PubMed  Google Scholar 

  • Thomas PA, Kalavathy CM, Abraham DJ, Rajasekaran J (1987) Oral ketoconazole in Keratomycosis. Indian J Ophthalmol 35(4):197–203

    CAS  PubMed  Google Scholar 

  • Torres MA, Mohamed J, Cavazos-Adame H, Martinez LA (1985) Topical ketoconazole for fungal keratitis. Am J Ophthalmol 100(2):293–298, trial. Cornea 2012; 31: 662–67

    Article  CAS  PubMed  Google Scholar 

  • Torres HA, Hachem RY, Chemaly RF, Kontoyiannis DP, Raad II (2005) Posaconazole: a broad-spectrum triazole antifungal. Lancet Infect Dis 5(12):775–785

    Article  CAS  PubMed  Google Scholar 

  • Tu EY, McCartney DL, Beatty RF, Springer KL, Levy J, Edward D (2007) Successful treatment of resistant ocular fusariosis with posaconazole (SCH-56592). Am J Ophthalmol 143(2):222–227

    Article  CAS  PubMed  Google Scholar 

  • Uchida K, Abe S, Yamaguchi H (2006) The postantifungal effect (PAFE) of itraconazole, in comparison with those of miconazole and fluconazole, on Candida species. Microbiol Immunol 50(9):679–685

    Article  CAS  PubMed  Google Scholar 

  • Ullmann AJ, Cornely OA, Burchardt A, Hachem R, Kontoyiannis DP, Töpelt K, Courtney R, Wexler D, Krishna G, Martinho M, Corcoran G, Raad I (2006) Pharmacokinetics, safety, and efficacy of posaconazole in patients with persistent febrile neutropenia or refractory invasive fungal infection. Antimicrob Agents Chemother 50(2):658–666

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Urbak SF, Degn T (1994) Fluconazole in the management of fungal ocular infections. Ophthalmologica 208(3):147–156

    Article  CAS  PubMed  Google Scholar 

  • Vermes A, Guchelaar HJ, Dankert J (2000) Flucytosine: a review of its pharmacology, clinical indications, pharmacokinetics, toxicity and drug interactions. J Antimicrob Chemother 46(2):171–179

    Article  CAS  PubMed  Google Scholar 

  • Wagner C, Graninger W, Presterl E, Joukhadar C (2006) The echinocandins: comparison of their pharmacokinetics, pharmacodynamics and clinical applications. Pharmacology 78(4):161–177

    Article  CAS  PubMed  Google Scholar 

  • Weinstein M, Reller L, Murphy J, Lichtenstein KA (1983) The clinical significance of positive blood cultures: a comprehensive analysis of 500 episodes of bacteremia and fungemia in adults. I. Laboratory and epidemiologic observations. Rev Infect Dis 5(1):35–53

    Article  CAS  PubMed  Google Scholar 

  • Wellington M, Gigliotti F (2001) Update on antifungal agents. Pediatr Infect Dis J 20(10):993–995

    Article  CAS  PubMed  Google Scholar 

  • Wood TO, Williford W (1976) Treatment of keratomycosis with amphotericin B 0.15%. Am J Ophthalmol 81(6):847–849

    Article  CAS  PubMed  Google Scholar 

  • Xuguang S, Zhixin W, Zhiqun W, Shiyun L, Ran L (2007) Ocular fungal isolates and antifungal susceptibility in northern China. Am J Ophthalmol 143(1):131–133

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi H, Abe S, Tokuda Y (1993) Immunomodulating activity of antifungal drugs. Ann N Y Acad Sci 685:447–457

    Article  CAS  PubMed  Google Scholar 

  • Yee RW, Cheng CJ, Meenakshi S, Ludden TM, Wallace JE, Rinaldi MG (1997) Ocular penetration and pharmacokinetics of topical fluconazole. Cornea 16(1):64–71

    Article  CAS  PubMed  Google Scholar 

  • Yilmaz S, Maden A (2005) Severe fungal keratitis treated with subconjunctival fluconazole. Am J Ophthalmol 140(3):454–458

    Article  CAS  PubMed  Google Scholar 

  • Yoon KC, Jeong IY, Im SK, Chae HJ, Yang SY (2007) Therapeutic effect of intracameral amphotericin B injection in the treatment of fungal keratitis. Cornea 26(7):814–818

    Article  PubMed  Google Scholar 

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Joseph, J., Sharma, S. (2016). Antifungal Therapy in Eye Infections: New Drugs, New Trends. In: Basak, A., Chakraborty, R., Mandal, S. (eds) Recent Trends in Antifungal Agents and Antifungal Therapy. Springer, New Delhi. https://doi.org/10.1007/978-81-322-2782-3_9

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